Book Whole Ross Nutrition Support Protocol

To order products in the Ross Metabolic Formula System, call:
1-800-551-5838
8:30 AM - 5:00 PM EST, Monday - Friday, except holidays.
For answers to questions about nutrition management of patients with

inherited metabolic disorders, call the Ross Metabolic Hotline:
1-800-986-8755.
The Ross Metabolic Formula System
Nutrition Support Protocols
4th Edition
The Ross Metabolic Formula System
Nutrition Support Protocols, 4th Edition
Authors:
Phyllis B. Acosta, Dr PH, RD, LD
Steven Yannicelli, PhD, RD, LD
Medical Director, Medical and Regulatory Affairs

Russell J. Merritt, MD, PhD
Vice President, Medical and Regulatory Affairs

William C. MacLean, MD
Manuscript Processor:
Christine K. Downs
Ross Products Division

Division of Abbott Laboratories
Columbus, Ohio 43216
Library of Congress, Catalog Card No 97-066096

© 2001 Abbott Laboratories
Price: $500
The product information contained here, although accurate at the time of publication, is subject to change.
The most current information may be obtained by referring to product labels.
A6224/(500)/June, 2001 LITHO IN USA

Acknowledgments
The shared experience of many clinicians has made possible the publication of the Ross Metabolic
Formula System Nutrition Support Protocols. We are particularly indebted, however, to three clinicians
listed below:
Vyoone Lewis, PhD, RD, Adjunct Professor, Pediatrics and Public Health and Tropical Medicine,
Tulane University, reviewed and made many excellent suggestions for improvement of Protocol 7,
"Nutrition Support of Infants, Children, and Adults with ß-Ketothiolase Deficiency."
Fran Rohr, MS, RD, in the Division of Clinical Genetics at The Children's Hospital, Boston, helped
prepare Protocol 9 "Nutrition Support of Infants, Children and Adults with Glutaric Aciduria Type I."
Sandy van Calcar, MS, RD, Nutritionist at the Metabolic Clinic, Biochemical Genetics Program,
University of Wisconsin helped prepare Protocol 20 for nutrition support of very long-chain-, long-chain-,
and long-chain-hydroxyacyl-CoA dehydrogenase deficiencies. She may be reached at 608/263-5981 if
you need to discuss these disorders further.
In addition, we thank the following physicians and nutritionists who reviewed and critiqued drafts of
protocols:
Karen Amorde-Spalding, MS, RD Reuben Matalon, MD, PhD

Children's Hospital Department of Pediatrics
Oakland, CA The University of Texas Medical Branch
Galveston, TX
Georgianne Arnold, MD Kimberlee Matalon, PhD, RD
Division of Genetics Department of Human Development
University of Rochester Medical Center University of Houston
Rochester, NY Houston, TX
Paul M Fernhoff, MD Shideh Mofidi, MS, RD
Division of Medical Genetics Westchester Institute for Human Development
Department of Pediatrics Valhalla, NY
Emory University School of Medicine
Atlanta, GA
Carol Greene, MD Maria Nardella, MA, RD
Children's National Medical Center Office of Children With Special Health Care Needs
Washington, DC Washington Department of Health
Olympia, WA
Harry Greene, MD Vivian Shih, MD
Medical Director, Slim Fast® Foods Company Massachusetts General Hospital
West Palm Beach, FL Boston, MA
L. Lyndon Key, Jr, MD, FAAP
Chief, Division of Pediatric Endocrinology
Department of Pediatrics
Medical University of South Carolina
Charleston, SC
Ross Products Division welcomes comments for additions or changes to this manual. Please address all
suggestions and inquiries to:
Phyllis B. Acosta, Dr PH, RD or Steven Yannicelli, PhD, RD
Director, Metabolic Diseases Clinical Research Scientist
614/624-7516; 800/986-8755 614/624-7648; 800/986-8755
Ross Products Division/Abbott Laboratories

P O Box 1317
Columbus, OH 43216-1317
© 2001 Ross Products Division iii

Contents
Page
Practical Aspects of Nutrition Support of Inborn Errors of Metabolism........................................vii
DISORDERS OF AMINO ACID METABOLISM

Aromatic Amino Acids
PROTOCOL 1 — Phenylketonuria (PKU) Nutrition Support of Infants, Children, and Adults With
PHENEX™-1 and PHENEX™-2 Amino Acid-Modified Medical Foods................... 1
PROTOCOL 2 — Maternal Phenylketonuria (MPKU) Nutrition Support of Pregnant Women With
Phenylketonuria (PKU) With PHENEX™-2 Amino Acid-Modified Medical Food .. 33
PROTOCOL 3 — Tyrosinemia Types Ia and Ib Nutrition Support of Infants, Children and Adults
With TYREX ®-1 and TYREX ®-2 Amino Acid-Modified Medical Foods.............. 49
PROTOCOL 4 — Tyrosinemia Types II and III Nutrition Support of Infants, Children, and Adults With
TYREX ®-1 and TYREX ®-2 Amino Acid-Modified Medical Foods ...................... 63
Branched-chain amino Acids

PROTOCOL 5 — Maple Syrup Urine Disease (MSUD) Nutrition Support of Infants, Children, and
Adults With KETONEX ®-1 and KETONEX ®-2 Amino Acid-Modified
Medical Foods..................................................................................................... 74
PROTOCOL 6 — Disorders of Leucine Catabolism Nutrition Support of Infants, Children, and Adults
With I-VALEX ®-1 and I-VALEX ®-2 Amino Acid-Modified Medical Foods ........ 103
PROTOCOL 7 — Mitochondrial Acetoacetyl-CoA Thiolase Deficiency (ß-Ketothiolase Deficiency)
Nutrition Support of Infants, Children, and Adults With KETONEX ®-1 and
KETONEX ®-2 Amino Acid-Modified Medical Foods......................................... 123
Sulfur Amino Acids

PROTOCOL 8 — Homocystinuria Nutrition Support of Infants, Children, and Adults With
HOMINEX ®-1 and HOMINEX ®-2 Amino Acid-Modified Medical Foods........... 137
Other Amino Acids

PROTOCOL 9 — Glutaric Aciduria Type I or 2-Ketoadipic Aciduria Nutrition Support of Infants,
Children, and Adults With GLUTAREX ®-1 and GLUTAREX ®-2 Amino Acid-
Modified Medical Foods .................................................................................... 166
PROTOCOL 10 — Glutaric Acidemia Type II (Multiple Acyl-CoA Dehydrogenase Deficiency)
Nutrition Support of Infants, Children, and Adults With PROVIMIN ® Protein-
Vitamin-Mineral Formula Component With Iron................................................. 196
PROTOCOL 11 — Lysinuric Protein Intolerance Nutrition Support of Infants, Children, and
Adults With PRO-PHREE ® Protein-Free Energy Module With Iron,
Vitamins & Minerals .......................................................................................... 209
PROTOCOL 12 — Nonketotic Hyperglycinemia Nutrition Support of Infants, Children, and
Adults With PRO-PHREE ® Protein-Free Energy Module With Iron,
Vitamins & Minerals .......................................................................................... 220
PROTOCOL 13 — Propionic or Methylmalonic Acidemia Nutrition Support of Infants, Children, and
Adults With PROPIMEX ®-1 and PROPIMEX ®-2 Amino Acid-Modified
Medical Foods................................................................................................... 230
DISORDERS OF CARBOHYDRATE METABOLISM

PROTOCOL 14 — Galactosemia Nutrition Support of Infants, Children, and Adults With ISOMIL ®
Soy Formula Powder With Iron ......................................................................... 262
PROTOCOL 15 — Glucose Transport Protein Defect, Pyruvate Dehydrogenase Complex Deficiency,
and Intractable Seizures Nutrition Support of Infants, Children, and Adults With
RCF ® Ross Carbohydrate-Free Soy Formula Base With Iron or ProViMin ®
Protein-Vitamin-Mineral Formula Component With Iron Powder........................ 279
iv © 2001 Ross Products Division

Page
PROTOCOL 16 — Glycogen Storage Disease Types Ia and Ib Nutrition Support of Infants,
Children, and Adults With RCF ® Ross Carbohydrate-Free Soy Formula Base
With Iron or ProViMin ® Protein-Vitamin-Mineral Formula Component With
Iron Powder ....................................................................................................... 296
PROTOCOL 17 — Hereditary Fructose Intolerance Nutrition Support of Infants,
Children, and Adults .......................................................................................... 313
PROTOCOL 18 — Pyruvate Carboxylase Deficiency Nutrition Support of Infants and Children With
PROVIMIN ® Protein-Vitamin-Mineral Formula Component With Iron ............... 325
DISORDERS OF LIPID METABOLISM

PROTOCOL 19 — Fasting Chylomicronemia Nutrition Support of Infants, Children, and Adults
With PROVIMIN ® Protein-Vitamin-Mineral Formula Component With Iron....... 338
PROTOCOL 20 — Mitochondrial Fatty Acid Oxidation Defects Nutrition Support of Infants, Children,
and Adults With PROVIMIN ® Protein-Vitamin-Mineral Formula Component
With Iron............................................................................................................ 350
DISORDERS OF MINERAL METABOLISM
PROTOCOL 21 — Hypercalcemia Nutrition Support of Infants, Children, and Adults With
CALCILO XD® Low-Calcium/Vitamin D-Free Infant Formula With Iron.............. 366
DISORDERS OF NITROGEN METABOLISM
PROTOCOL 22 — Gyrate Atrophy of the Choroid and Retina Nutrition Support of Infants, Children,
and Adults With CYCLINEX ®-1 and CYCLINEX ®-2 Amino Acid-Modified
Medical Foods ................................................................................................... 379
PROTOCOL 23 — Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome Nutrition
Support of Infants, Children, and Adults With CYCLINEX ®-1 and
CYCLINEX ®-2 Amino Acid-Modified Medical Foods......................................... 406
PROTOCOL 24 — Urea Cycle Disorders Nutrition Support of Infants, Children, and Adults With
CYCLINEX ®-1 and CYCLINEX ®-2 Amino Acid-Modified Medical Foods ......... 418
APPENDICES
Nutrient Composition Tables
APPENDIX 1. Fatty Acid Profile of Infant/Toddler Metabolic Medical Foods ..................................... A-2
APPENDIX 2. Fatty Acid Profile of Child/Adult Metabolic Medical Foods .......................................... A-2
APPENDIX 3. Density of Metabolic Medical Foods ........................................................................... A-3
APPENDIX 4. Nutrient Composition of Alimentum ® Protein Hydrolysate Formula With Iron............ A-4
APPENDIX 5. Nutrient Composition of Isomil ® Soy Formula With Iron............................................ A-5
APPENDIX 6. Nutrient Composition of Similac ® With Iron Infant Formula....................................... A-6
APPENDIX 7. Nutrient Composition of NeoSure® and Similac® Lactose Free ................................. A-7
APPENDIX 8. Nutrient Composition of Mature Human Milk, Skim Milk, Whole Cow's Milk, and
Whole Egg......................................................................................................... A-8
APPENDIX 9. Nutrient Composition of Polycose ® Glucose Polymers and Pedialyte ® Oral
Electrolyte Maintenance Solution....................................................................... A-9
APPENDIX 10. Nutrient Composition of Selected Vegetable Oils...................................................... A-9
APPENDIX 11. Nutrient Composition of Vi-Daylin ® Multivitamin + Iron Drops and
Pro-Phree ® Protein-Free Energy Module with Iron, Vitamins, and Minerals.... A-10
APPENDIX 12. Nutrient Composition of Very-Low-Protein Foods per 100 g.................................... A-11
Recommended Dietary Allowances (RDIs)
APPENDIX 13. Recommended Dietary Intakes (RDIs) for Minerals and Vitamins by Infants........... A-14
APPENDIX 14. Recommended Dietary Intakes (RDIs) for Minerals and Vitamins by Children,
Adolescents, and Adults................................................................................... A-15
© 2001 Ross Products Division v

Page
Technical Information
APPENDIX 15. Mathematical Formula for Interconversion of Plasma Amino Acids Between
µmol/L and mg/dL ............................................................................................ A-17
APPENDIX 16. Molecular Weights of Amino Acids.......................................................................... A-17
APPENDIX 17. Selected Laboratory Standards ............................................................................... A-18
APPENDIX 18. Estimating Osmolarity of a Medical Food Mixture ................................................... A-20
APPENDIX 19. Approximate Osmolarity of Selected Foods ............................................................ A-21
APPENDIX 20. Potential Renal Solute Load of Medical Food Mixture ............................................. A-22
APPENDIX 21. NDC Numbers for Metabolic Medical Foods............................................................ A-23
Clinical Forms
APPENDIX 22. Diet Guide .............................................................................................................. A-24
APPENDIX 23. Evaluation of Mineral/Vitamin Content of Medical Food Mixture ............................. A-25
APPENDIX 24. Diet Diary................................................................................................................ A-26
APPENDIX 25. Directions for Recording the Diet Diary ................................................................... A-27
Supplier Information
APPENDIX 26. Sources of Nutrients and Drugs............................................................................... A-28
APPENDIX 27. Low-Protein Food Suppliers .................................................................................... A-29
APPENDIX 28. Products for Prescription Diet Management ............................................................ A-29
INDEX ........................................................................................................................... I-1
vi © 2001 Ross Products Division

Practical Aspects of Nutrition Support of Inborn Errors of Metabolism
The problem of assuring adequate nutrition for infants, children, and adults with inherited metabolic
disorders may be decreased by the use of a protocol — a plan for treatment — because each patient
requires individualized nutrition care. The protocols in this manual are intended to serve as guides for
health care professionals who treat infants, children, adolescents, adults, and pregnant women with
inherited metabolic disorders. The protocols have been developed for use with the Ross Metabolic
Formula System (RMFS). They will be particularly useful to those who are relatively unfamiliar with
nutrition support of metabolic disorders, although specialists working in treatment centers where
protocols are already established should find them useful as well.
Overview
The protocols are organized according to disorder, with the Appendix containing information about
recommended nutrient intakes for various age groups, laboratory standards, and other technical
information. Also included in the Appendix are sample forms for a Diet Guide and Diet Diary, which may
be photocopied for individual use.
The newcomer to treatment of metabolic disorders will benefit from scanning the entire volume,
giving attention not only to the protocol relevant to the disorder of interest and the Appendices, but also
to the "Technical Information" section in the Appendices.
Recommended Dietary Intakes (RDIs)
Protein requirements are greater than Dietary Reference Intakes (DRIs) when L-amino acids are the
primary protein source (2). This increased need is because of rapid amino acid absorption and
subsequent oxidation (11, 16, 27), resulting in poor linear growth (7, 30), and lower than normal nitrogen
retention (27), body protein, and nitrogen content of patients fed primarily L-amino acids (3).
Recommended mineral and vitamin intakes suggested for patients with inherited metabolic
disorders are the greatest intakes suggested for each age in the 1980 and 1989 National Academy of
Sciences National Research Council (NAS-NRC) Recommended Dietary Allowances (RDAs) (10) and
the DRIs (22). Reasons for choosing the greatest intakes recommended include reports of inadequate
linear growth (7, 30) and poor bone mineralization (17) with Food and Agriculture Organization/World
Health Organization (FAO/WHO)-recommended protein intakes (9); greater than normal energy needs
when L-amino acids supply the bulk of protein equivalent (23); and depressed plasma concentrations of
ferritin (5, 25), selenium (12), and zinc (1) when RDAs were achieved with chemically defined diets.
Measuring Medical Foods

All measures for dry powders referred to in this manual are US standard, level household measures.
Cups and spoons intended for measuring liquids should not be used to measure powders. Many
measuring cups and spoons sold in food markets are grossly inaccurate. If scales that read in grams are
not available, US standard measuring equipment for dry materials, calibrated by the US Bureau of
Standards, should be obtained (8). Professionals, parents and patients should be aware that density of
medical foods varies because of settling during shipping and differences in packing. Because of this
variability, medical foods should be weighed on a scale that reads in grams. Weighing takes the
guesswork out of determining whether the amount of medical food ingested was the same as that
prescribed.
Supplying Restricted Amino Acids

For infants younger than 4 months of age, restricted amino acids are normally supplied by iron-fortified
® ®
proprietary infant formulas such as Similac With Iron Infant Formula or Isomil Soy Formula With Iron.
Use of iron-fortified products enhances iron status of infants who may absorb less than normal amounts
of iron from elemental medical foods. Similac and Isomil are available in Ready to Feed, Concentrated
Liquid, and Powder forms.
Baby foods (beikost) should be added slowly to the diet as the infant becomes developmentally
ready — sometime between 3 and 4 months of age for the developmentally normal. Prescribed amounts
of selected baby foods, and, later, table foods gradually displace infant formula as the source of
restricted amino acid(s).
© 2001 Ross Products Division vii

Meeting Water Needs
Water needs of infants should be supplied by the medical food mixture. Children and adults may have
additional free water when they are thirsty, if both the osmolarity and potential renal solute load of their
medical food mixtures are in safe ranges. Appendices 18, 19, and 20, pp A-20 through A-22, provide
help in estimating these.
Recognizing the Maillard Reaction

The Maillard reaction is a name given to a complex group of chemical reactions in foods in which
reacting amino acids, peptides, and proteins condense with sugars, forming bonds for which no digestive
enzymes are available. The Maillard reaction is accelerated by heat. It is characterized in its initial stage
by a light-brown color, followed by buff yellow and then dark brown in the intermediate and final stages.
Caramel-like and roasted aromas develop. Preparers of medical foods need to be able to recognize the
Maillard reaction because it causes loss of some sugars and amino acids. For this reason, medical foods
should not be heated beyond 100o F. For babies in the newborn nursery and at home, the aseptic
technique of mixing medical foods should be used (24).
Monitoring Amino Acid Concentrations

Successful management of inherited disorders of metabolism requires frequent monitoring of
appropriate analytes. The recommendations for plasma amino acid concentrations given here are close
to the normal range because 30 years of practice have suggested that values as close to normal as
possible are best. In the past, normal values were difficult to achieve because of inadequate knowledge
of requirements and food composition, infrequent monitoring, and failure to recognize the effects of
infection, trauma, and catabolism on plasma amino acid concentrations.
Frequent monitoring of plasma amino acid concentrations and other analytes gives the physician
and nutritionist data that verify the adequacy of the nutrition support prescription. These data are also
useful in motivating patient/parent compliance with the prescription. Patients with insulin-dependent
diabetes often monitor blood glucose three times daily, so frequent monitoring of plasma amino acids
should pose no major problem.
Some centers may wish to draw blood to monitor plasma amino acids at times other than those
listed in these protocols. We recognize the need to take a practical approach to nutrition support. If
blood cannot be drawn 2 to 4 hours after feeding, local normal standards should be developed for
plasma amino acid concentrations. However, prolonged fasting may cause spurious elevations of
plasma amino acid concentrations that could lead to unwarranted diet changes (13, 14), and blood
drawn 15 minutes to 1 hour after a meal may also yield spuriously high values (11).
Tuning the Prescription

Beikost should be introduced into the diet when infants are between 3 and 4 months of age or when
developmentally ready. Delay in introduction of beikost or table foods beyond this "critical period" often
leads to great difficulty in getting the infant to accept them at a later age. The protocols in this manual
for disorders of amino acid metabolism make use of a system of exchanges in which the primary
restricted amino acid is used as the basis for providing specific amounts of food in each serving list.
Serving Lists are Breads and Cereals, Fats, Fruits, Vegetables, Free Foods A, and Free Foods B. Some
centers with extensive experience have developed their own food lists for each disorder; the Ross
Metabolic Formula System products can be safely prescribed here as well.
Amino acid intakes recommended in these protocols are ranges within which requirements for most
patients will fall; however, the requirement of each patient will differ, with some patients tolerating
the lower end of the range and others requiring the upper end. The specific requirement for each
patient must be determined by frequent evaluation of plasma amino acid and transthyretin
concentrations, growth, and skin and hair. Patients who are growing well due to adequate protein intake
can normally tolerate more of the restricted amino acid(s) than can poorly growing infants and children
(2, 20).
When the restricted amino acid concentration(s) is (are) elevated in blood or plasma, detective work
is required to determine the reason(s) for the elevation. Some questions that should be asked are given
below:
Is the prescribed diet ingested daily?
viii © 2001 Ross Products Division

Does the child fail to ingest significant amounts of prescribed medical food? Beikost or table food?
Is measuring equipment accurate and are foods carefully weighed or measured?
Is the appropriate form of infant formula (concentrated liquid, powder, ready-to-feed) mixed with the
medical food?
Do siblings, relatives, neighbors, or baby sitters feed the patient? If "yes," do they give foods not
prescribed, or prescribed foods in greater than prescribed amounts?
If the patient is in daycare or school, are peers, teachers, etc, giving the child food, or is the child
"trading" foods?
Has the patient eaten any foods NOT on the servings lists?
Is the child "snitching" food?
Is the child ill?
Appropriate monitoring and disciplining of the child (18) on a special diet from an early age are essential
to diet compliance. For additional information about this topic, see references 21 and 28.
Changing Medical Foods

RMFS infant/toddler medical foods are designed to supply the nutrient needs of infants and young
children when they are supplemented with enough iron-fortified infant formula or foods to provide the
restricted amino acid(s) in amounts necessary for normal growth and development. When a toddler's
appetite is small, RMFS infant/toddler medical food should be replaced by RMFS child/adult medical
food. This change may be immediate only if the RMFS medical food is promptly accepted by the child.
Many children, however, are slow to accept new flavors.
As infants grow into children, they become more sensitive to changes in flavors of foods, a
phenomenon that often complicates ingestion of medical foods. Because nutrient requirements change
gradually over time, the medical food does not need to be changed abruptly. If acceptance is slow, the
amount of RMFS child/adult medical food is gradually increased as the infant/toddler medical
food is gradually decreased. The change from infant/toddler to child/adult medical food may require a
few days or several months.
Masking the Taste of Free Amino Acids

Foods with free amino acids containing sulfur and those with acidic or basic groups have a sulfurous,
bitter, unpleasant taste that may make diet compliance difficult (26). Products containing free amino
acids taste best when they are served very cold. Patients will accept these products containing free
amino acids more easily if they are served as "slushes," that is, chilled almost to freezing.
Selecting Nutrient Analysis Computer Software

A number of different software packages are available for computer evaluation of nutrient intake. Many
software packages appear impressive because their databases contain a large number of nutrients;
however, some packages with many nutrients have significant missing data (6). For calculating diets of
infants, children, and adults with inherited metabolic disorders, we recommend Amino Acid Analyzer (4)
available from Ross Products Division of Abbott Laboratories.
General Principles of Nutrition Support of Genetic Disease

Specific enzymes produced under the direction of individual genes catalyze specific reactions as noted
in the following genetic and metabolic sequences. A is converted to D through intermediates B and C
using enzymes AB, BC, and CD:
© 2001 Ross Products Division ix

If enzyme CD were genetically impaired, at least six pathophysiologic consequences could result:
G ene A B Gene BC G ene C D
Enzym e A B Enzym e B C Enzym e C D
A B C D
1. A deficiency of product D or some compound derived only from D. For example, in

phenylketonuria (PKU), phenylalanine (PHE) is not hydroxylated to form tyrosine (TYR). Not only is the
accumulated PHE toxic, but TYR becomes an essential nutrient. TYR must be supplemented to
maintain proper growth and plasma TYR concentrations in the nutrition support of patients with PKU.
2. A loss of feedback control. If product D normally functions in feedback control of enzyme AB,
overproduction of an intermediate product may occur because D is not present in amounts necessary to
regulate production of intermediates B and C.
3. An accumulation of C, the immediate precursor of the blocked reaction. In maple syrup urine
disease (MSUD), toxic branched-chain-α-ketoacids accumulate because they cannot be decarboxylated
and transacylated to their coenzyme A-acyl derivatives. The consequence in the neonate is severe
central nervous system depression with apnea, stupor, coma, and death. If the neonate survives, mental
retardation or death ensues if the child is not treated by diet restriction within 3 to 5 days of life.
4. An accumulation of A or B, remote precursors of the blocked reaction sequence CD. If the
preceding reactions are freely reversible, a precursor in addition to that proximal to the block will
accumulate. This process is illustrated in MSUD by increased leucine (LEU), isoleucine (ILE), and valine
(VAL), which are formed by reamination of the branched-chain-α-ketoacids — α-ketoisocaproic, α-keto-
β-methylvaleric, and α-ketoisovaleric acids, respectively.
5. Increased production of alternative product (eg, E, through little-used metabolic pathways.

When PHE accumulates because of impaired phenylalanine hydroxylase, phenylpyruvic, phenylacetic,
and phenyllactic acids are produced in greater than normal amounts through existing pathways that
normally do not function at physiologic concentrations of cellular PHE.
6. Inhibition of alternative pathways by accumulated substrate (eg, C in CD impairment). For

example, neurotransmitter synthesis may be depressed in PKU owing to increased blood PHE
concentrations that inhibit tyrosine hydroxylase and tryptophan hydroxylase in the central nervous
system. Another example is type Ia tyrosinemia. The accumulation of succinylacetone inhibits δ-
aminolevulinic acid (δ-ALA) dehydratase and results in secondary accumulation of δ-ALA, attacks of
acute porphyria with peripheral neuropathy, hypertension, and bizarre behavior.
Nine approaches to nutrition support of inborn errors of metabolism are discussed below. The
appropriate approach depends on the biochemistry and pathophysiology of disease expression —
several therapeutic approaches may be used simultaneously.
1. Enhancing anabolism and depressing catabolism. This involves the use of adequate amounts
of appropriate medical food and other foods to supply protein and energy, and administration of insulin,
x © 2001 Ross Products Division

if needed. Fasting should be prevented. This therapeutic measure should be used in all patients with an
inborn error involving catabolic pathways.
2. Correcting the primary imbalance in metabolic relationships. This correction involves reducing,
through diet restriction, the accumulation of substrate that is toxic. This approach is used in PKU where
PHE, and MSUD where LEU, ILE, and VAL are limited.
3. Providing alternative metabolic pathways to decrease accumulated toxic precursors in

blocked reaction sequences. In the treatment of isovaleric acidemia, innocuous isovalerylglycine is
formed from accumulating isovaleric acid if supplemental glycine is provided to drive glycine-N-
transacylase. Isovalerylglycine is excreted in the urine.
4. Supplying products of blocked primary pathways. As examples, arginine (ARG) is supplied in

most disorders of the urea cycle, cystine (CYS) is supplied in homocystinuria (HCU), TYR in PKU,
tetrahydrobiopterin in biopterin synthetic defects, and ether lipids in patients with some peroxisomal
disorders.
5. Supplementing "conditionally essential" nutrients. Carnitine, CYS, and TYR are supplemented
in secondary liver disease, and carnitine is supplemented in organic acidemias.
6. Stabilizing altered enzyme proteins. The rate of biologic synthesis and degradation of
holoenzymes depends on their structure. In some holoenzymes, saturation by coenzyme increases their
biologic half-life and, thus, overall enzyme activity at the new equilibrium. This therapeutic mechanism
is used in HCU and MSUD. Pharmacologic intakes of pyridoxine in HCU and thiamin in MSUD increase
intracellular pyridoxal phosphate and thiamin pyrophosphate and increase the specific activity of
cystathionine ß-synthase and branched-chain-α-ketoacid dehydrogenase complex.
7. Replacing deficient cofactors. Many vitamin-dependent disorders are caused by blocks in
coenzyme production and are "cured" by pharmacologic intake of a specific vitamin precursor. This
mechanism presumably involves overcoming a partially impaired enzyme reaction by mass action.
Impairment of reactions required to produce either methylcobalamin or adenosylcobalamin result in
HCU and/or methylmalonic aciduria (MMA). Daily intakes of appropriate forms of milligram quantities of
vitamin B12 may cure the disease.
8. Inducing enzyme product. If the structural gene or enzyme is intact, but suppressor, enhancer, or
promoter elements are not functional, abnormal amounts of enzyme may be produced. The structural
gene may be "turned on" or "turned off" to enable normal enzymatic production to occur. In the acute
porphyria of tyrosinemia type Ia, excessive δ-ALA production may be reduced by suppressing
transcription of the δ-ALA synthase gene with excess glucose.
9. Supplementing nutrients that are inadequately absorbed or not released from their
apoenzyme. Examples are zinc in acrodermatitis enteropathica and biotin in biotinidase deficiency.
The Table that follows provides information, by disorder, on appropriate Ross Products or other products
to use for nutrition support of a variety of inborn errors of metabolism.
© 2001 Ross Products Division xi

xii
TABLE A. Nutrition Support of Selected Inborn Errors of Metabolism
Inborn Error and Defect Nutrient(s) To Modify Vitamin-Responsive Ross Metabolic

Formula/Other
INBORN ERRORS OF AMINO ACID METABOLISM
Aromatic Amino Acids
Alcaptonuria (homogentisic acid oxidase) Restrict phenylalanine (PHE) and tyrosine (TYR). No Tyrex-2
Phenylketonuria (PKU) and Restrict PHE and increase TYR. Maintain protein No Phenex-1
Hyperphenylalaninemia (phenylalanine hydroxylase) intake above NAS-NRC RDAs for age. Phenex-2
Hyperphenylalaninemia (dihydropteridine reductase); Restrict PHE and increase TYR. Maintain protein Yes; tetrahydrobiopterin, Phenex-1
GTP cyclohydrolase I; pyruvolyltetrahydropterin intake above NAS-NRC RDAs for age. 2 mg/kg/day. Phenex-2
synthase)
Tyrosinemia type Ia (fumarylacetoacetate Restrict PHE and TYR. Maintain protein and energy No Tyrex-1
hydrolyase) intakes above NAS-NRC RDAs for age. Tyrex-2
Tyrosinemia type Ib (maleylacetoacetate isomerase) Restrict PHE and TYR. Maintain protein and energy No Tyrex-1
intakes above NAS-NRC RDAs for age. Tyrex-2
Tyrosinemia types II and III (tyrosine Restrict PHE and TYR. Maintain protein and energy No Tyrex-1
aminotransferase) intakes above NAS-NRC RDAs for age. Tyrex-2
Branched-chain amino Acids
ß-Ketothiolase deficiency Restrict ILE. Maintain protein and energy intakes No Ketonex-1
above NAS-NRC RDAs for age. Administer L- Ketonex-2
carnitine (both must be
supplemented with
LEU and VAL)
Maple syrup urine disease (MSUD) (branched-chain- Restrict ILE, LEU, and VAL. Maintain protein and Yes; thiamin-responsive if anyKetonex-1
ketoacid [BCKA] dehydrogenase complex) energy intakes above NAS-NRC RDAs for age. residual enzyme activity. Ketonex-2
Response to thiamin
inadequate to alleviate need
for restriction of branched-
chain amino acids. 100 to
300 mg of ORAL thiamin
daily.
3-Hydroxyisobutyric aciduria (3-Hydroxyisobutyric Restrict VAL. Administer L-carnitine. Maintain No Ketonex-1
acid dehydrogenase) protein and energy intakes above NAS-NRC Ketonex-2 (both must
© 2001 Ross Products Division
RDAs for age. be supplemented

with ILE and LEU)
Isovaleric acidemia (isovaleryl-CoA dehydrogenase); Restrict LEU. Administer L-carnitine and glycine No I-Valex-1
3-Methylcrotonylglycinuria (3-methylcrotonyl-CoA (GLY). Maintain protein and energy intakes I-Valex-2
carboxylase) above NAS-NRC RDAs for age.
3-Methylglutaconic aciduria (3-methylglutaconyl-CoA Restrict LEU. Administer L-carnitine and GLY Yes, pantothenic acid, 15- I-Valex-1
hydratase) Maintain protein and energy intakes above NAS- 150 mg/day I-Valex-2
NRC RDAs for age.

Formula/Other
3-Hydroxy-3-methylglutaric aciduria (3-hydroxy-3- Restrict LEU and fat. Maintain protein and energy No I-Valex-1
methylglutaryl-CoA lyase) intakes above NAS-NRC RDAs for age. I-Valex-2
Sulfur Amino Acids
Homocystinuria, pyridoxine nonresponsive Restrict MET; increase cystine (CYS); supplement No Hominex-1
(cystathionine ß-synthase) folate and betaine. Maintain protein intake above Hominex-2
NAS-NRC RDAs for age.
Homocystinuria, pyridoxine-responsive Pyridoxine. Yes; 25 to 1,000 mg of ORAL None indicated
(Cystathionine ß-synthase) pyridoxine daily. Use
smallest amount that results
in biochemical normalcy as
excess may cause
peripheral neuropathy.
Other Inborn Errors of Amino Acid Metabolism
Glutaric aciduria type I (glutaryl-CoA Restrict lysine (LYS) and tryptophan (TRP). Yes; some patients may have a Glutarex-1
dehydrogenase) Administer L-carnitine. Maintain protein intake partial response to ORAL Glutarex-2
above NAS-NRC RDAs for age. riboflavin, 100 to 300 mg
daily in small doses
administered with food.
Glutaric acidemia type II (multiple acyl-CoA Restrict protein and fat. Administer L-carnitine, and Yes? Prescribe 100 to 300 mg Pro-Phree
dehydrogenase) GLY. Maintain energy intake above NAS-NRC ORAL riboflavin daily in ProViMin
RDAs for age. small doses with food.
2-Ketoadipic aciduria (2-ketoadipic dehydrogenase) Restrict LYS and TRP. Administer L-carnitine. No Glutarex-1
Maintain protein intake above NAS-NRC RDAs Glutarex-2
for age.
Lysinuric protein intolerance (defect in renal, Restrict protein. Supplement with L-citrulline (CIT). No Pro-Phree
intestinal, and hepatic membrane transport of Maintain energy intake above NAS-NRC RDAs
dibasic amino acids) for age.
Methylmalonic acidemia (methylmalonyl-CoA Restrict ILE, MET, threonine (THR), VAL, odd- No Propimex-1
mutase º or —) chain-fatty acids, and long-chain-unsaturated Propimex-2
fatty acids. Maintain protein and energy intakes
above NAS-NRC RDAs for age.
Methylmalonic acidemia (cobalamin reductase; Minimum restriction of ILE, MET, THR, and VAL. Yes; 1 to 2 mg Propimex-1
adenosyltransferase) Administer L-carnitine. hydroxycobalamin daily. Propimex-2
Nonketotic hyperglycinemia (one of four protein Restrict protein. Maintain energy intake above NAS- No Pro-Phree
components [P, H, T, or L] of a multienzyme NRC RDAs for age. Similac
complex in the mitochondrial GLY cleavage Isomil
system) Alimentum
xiii
xiv

Formula/Other
Propionic acidemia (propionyl-CoA carboxylase) Restrict ILE, MET, THR, VAL, odd-chain-fatty acids, Yes? Questionable; some Propimex-1
and long-chain-unsaturated fatty acids. clinicians supplement with Propimex-2
Administer L-carnitine. Maintain protein and 5 to 10 mg ORAL D-biotin
energy intakes above NAS-NRC RDAs for age. daily.
INBORN ERRORS OF CARBOHYDRATE METABOLISM
Galactosemias
Epimerase deficiency Delete galactose, add specific known amount of No Health Source
galactose if no epimerase activity. Maintain Isomil Powder
protein and energy intakes at NAS-NRC RDAs
for age.
Galactokinase deficiency Delete galactose. Maintain protein and energy No Health Source
intakes at NAS-NRC RDAs for age. Isomil Powder
Galactose-1-phosphate uridyl transferase deficiency Delete galactose. Maintain protein and energy No Health Source
intakes at NAS-NRC RDAs for age. Isomil Powder
Glucose transport protein deficiency (GLUT1) Restrict carbohydrate (CH2O). High-fat, ketogenic No ProViMin
diet. RCF
Glycogen Storage Diseases
GSD Type Ia (glucose-6-phosphatase); Avoid lactose, fructose and sucrose. Modify type of No ProViMin
GSD Type Ib (defective glucose-6-phosphate CH2O and frequency of feeds. Maintain protein Polycose
transport) and energy intakes at NAS-NRC RDAs for age. RCF
Raw cornstarch after 6
to 9 mos of age
GSD Type III (amylo-1, 6-glucosidase) Provide high protein. Avoid lactose, fructose and No Polycose
sucrose. Supplement with L-alanine (ALA). ProViMin
Modify type of CH2O and frequency of feeds. RCF
Maintain energy intake at NAS-NRC RDAs for Raw cornstarch after 6
age. to 9 mos of age
GSD Type IV (α-1, 4-Glucan α-1, 4-glucan 6- Provide high protein unless cirrhosis present. No ProViMin
glucosyltransferase) Modify type of CH2O and frequency of feeds. RCF
Maintain energy intakes at NAS-NRC RDAs for Polycose
age. Raw cornstarch after 6
to 9 mos of age
GSD Type V (muscle phosphorylase) Provide high protein. Supplement L-ALA. Maintain No ProViMin
energy intake at NAS-NRC RDAs for age. RCF
Hereditary Fructose Intolerance
Hereditary fructose intolerance (aldolase B) Restrict fructose to < 10 mg/kg of body weight; No Pro-Phree
restrict protein if liver damage. Maintain energy Similac for infants
intake at NAS-NRC RDAs for age. Cow's milk for children

Formula/Other
Pyruvate Dehydrogenase Complex Deficiency Restrict CH2O. High-fat, ketogenic diet. Yes? Thiamin. ProViMin
(E1α or E1β) RCF
Pyruvate carboxylase deficiency Moderate protein, CH2O, fat. Administer thiamin, No ProViMin
citrate, and possibly L-ASP acid, L-asparagine,
L-glutamic acid, and L-glutamine.
Seizures Restrict CH2O. High-fat, ketogenic diet. No ProViMin
RCF
INBORN ERRORS OF CHOLESTEROL METABOLISM
Smith-Lemli-Opitz syndrome (microsomal 7- Supplement cholesterol, > 50 mg/kg body weight; increase No Any tolerated
energy intake to amount required for adequate weight gain
dehydrocholesterol reductase) (19)
INBORN ERRORS OF FATTY ACID OXIDATION
Disorders of Mitochondrial Fatty Acid Oxidation
Carnitine-acylcarnitine translocase deficiency (15) Restrict fat; limit MCT. Provide adequate essential No ProViMin
fatty acids. Administer L-carnitine; prevent fasting
Very-long-chain and long-chain-acyl-CoA Restrict long-chain-fatty acids (> 14 carbons) to 15% No ProViMin
dehydrogenase deficiencies; of energy. Avoid fasting. Provide adequate protein
Long-chain-hydroxyacyl-CoA dehydrogenase and energy. Supplement fractionated coconut oil
deficiency and L-carnitine. Supplement docosahexaenoic acid
(DHA) in patients with long-chain-hydroxyacyl-CoA
dehydrogenase deficiency.
Medium-chain-acyl-CoA dehydrogenase deficiency Restrict fat to 20% to 30% of energy. Avoid fasting. No ProViMin
Provide adequate protein and energy. Supplement
L-carnitine.
Short-chain and short-chain-hydroxyacyl-CoA Restrict fat to 20% to 30% of energy. Avoid fasting. No ProViMin
dehydrogenase deficiencies Provide adequate protein and energy. Supplement
L-carnitine
INBORN ERRORS OF LIPOPROTEIN METABOLISM
Abetalipoproteinemia and hypobetalipoproteinemia Restrict triglycerides with long-chain-fatty acids. No ProViMin
(Apo B, absence and decreased) Supplement with vitamins A, D, E and K and Polycose
linoleic and α-linolenic acids. Maintain protein and
energy intakes at NAS-NRC RDAs for age.
Lecithin:cholesterol acyltransferase deficiency Restrict fat. Maintain protein and energy intakes at No ProViMin
(LCAT) NAS-NRC RDAs for age. Polycose
Hyperlipoproteinemias
Type I (extrahepatic lipoprotein lipase; Apo C-II Restrict triglycerides with long-chain-fatty acids to 8% No ProViMin
absent or decreased; lipoprotein lipase inhibitors) to 15% of energy. Maintain protein and energy Polycose
intakes at NAS-NRC RDAs for age.
xv
xvi

Formula/Other
Type IIa (LDL receptors absent or defective) Restrict cholesterol and saturated fat; increase No Isomil
polyunsaturated fatty acids (PUFAs). Maintain ProViMin
protein and energy intakes at NAS-NRC RDAs RCF
for age. Polycose
Type IIb Restrict cholesterol, saturated fat, mono- and No ProViMin
disaccharides, and alcohol. Increase PUFAs and RCF
fiber. Maintain protein and energy intakes at Polycose
NAS-NRC RDAs for age.
Type III (hepatic lipoprotein lipase; homozygous for Restrict cholesterol, saturated fat, mono- and No ProViMin
abnormal Apo E2; remnant receptor defect) disaccharides, and alcohol. Increase PUFAs and RCF
fiber. Restrict energy if patient is overweight. Polycose
Maintain protein intake at NAS-NRC RDAs for
age.
INBORN ERRORS OF MINERAL METABOLISM
Idiopathic hypercalcemia with supravalvular aortic Restrict calcium and vitamin D. No Calcilo XD
stenosis — Williams syndrome.
Osteopetrosis Restrict calcium and vitamin D. No Calcilo XD
Sulphite oxidase deficiency (29) Restrict cystine and methionine No Pro-Phree
INBORN ERRORS OF NITROGEN METABOLISM
Carbamylphosphate synthetase deficiency; Restrict protein. Supplement with essential amino No Cyclinex-1
Ornithine transcarbamylase deficiency acids (EAAs), L-carnitine, and L-CIT. Maintain Cyclinex-2
energy intake above NAS-NRC RDAs for age.
Citrullinemia (argininosuccinate synthetase); Restrict protein. Supplement with EAAs, L-carnitine, No Cyclinex-1
Argininosuccinic aciduria (argininosuccinate lyase) and L-ARG. Maintain energy intake above NAS- Cyclinex-2
NRC RDAs for age.
Argininemia (arginase) Restrict protein. Supplement with EAAs and No Cyclinex-1
L-carnitine. Maintain energy intake above NAS- Cyclinex-2
NRC RDAs for age.
Gyrate atrophy (ornithine-∆-aminotransferase) Restrict arginine (ARG) and protein. Supplement Yes; pyridoxine. Cyclinex-1
with EAAs and L-carnitine. Maintain energy Cyclinex-2
intake above NAS-NRC RDAs for age.
Hypernornithinemia - hyperammonemia - Restrict protein. Supplement with L-ARG, L-CIT, or No Cyclinex-1
homocitrullinuria syndrome (HHH syndrome) L-ornithine (ORN). Maintain energy intake above Cyclinex-2
(defective ornithine transport across mitochondrial NAS-NRC RDAs for age.
membrane)
N-acetylglutamate synthetase deficiency Restrict protein. Supplement with EAAs, L-carnitine, No Cyclinex-1
and N-carbamylglutamate. Maintain energy Cyclinex-2
intake above NAS-NRC RDAs for age.
References
1. Acosta PB, Fernhoff PM, Warshaw HS, et al: Zinc status and growth of children undergoing treatment for
phenylketonuria. J Inher Metab Dis 1982;5:107-110.
2. Acosta PB, Yannicelli S: Protein intake affects phenylalanine requirements and growth of infants with
phenylketonuria. Acta Paediatr 1994; (Suppl):407:66-67.
3. Allen JR, Baur LA, Waters DL, et al: Body protein in prepubertal children with phenylketonuria. Eur J Clin Nutr
1996;50:178-186.
4. Amino Acid Analyzer© is available from Ross Products Division, Appendix 28, p A-29.
5. Bodley JL, Austin VJ, Hanley WB, et al: Low iron stores in infants and children with treated phenylketonuria: A
population at risk for iron-deficiency anaemia and associated cognitive deficits. Eur J Pediatr 1993;152:140-143.
6. Byrd-Bredbenner C: Computer nutrient analysis software packages: Considerations for selection. Nutr Today
1988; September-October:13.
7. Dhondt JL, Largilliere C, Moreno L, Farriaux JP: Physical growth in patients with phenylketonuria. J Inher Metab
Dis 1995;18:135-137.
8. Dietetic scales that weigh in grams are available from Pelouze Scales Co, PO Box 1058, Evanston, IL 60204. For
ordering information, see Appendix 28, p A-29.
9. FAO/WHO/UNU Expert Consultation: Energy and Protein Requirements. Geneva: World Health Organization,
1985.
10. Food and Nutrition Board, Committee on Dietary Allowances: Recommended Dietary Allowances, eds 9 and 10.
Washington, DC: National Academy of Sciences, 1980 and 1989.
11. Gropper S, Acosta PB: Effect of simultaneous ingestion of L-amino acids and whole protein on plasma amino
acids and urea nitrogen concentrations in humans. JPEN 1991;15:48-53.
12. Gropper S, Acosta PB, Clarke-Sheehan N, et al: Trace element status of children with PKU and normal children.
J Amer Diet Assoc 1988;88:459-464.
13. Gropper SS, Gropper DM, Acosta PB: Plasma amino acid response to ingestion of L-amino acids and whole
protein. J Pediatr Gastroenterol Nutr 1993;16:143-150.
14. Guttler F, Olseson ES, Wamberg E: Diurnal variations of serum phenylalanine in phenylketonuric children on low
phenylalanine diet. Am J Clin Nutr 1969;22:1568-1570.
15. Haworth JC, Demaugre F, Booth FA, et al: A typical features of the hepatic form of carnitine palmitoyltransferase
deficiency in a Hutterite family. J Pediatr 1992;121;553-557.
16. Herrmann ME, Broesicke HG, Keller M, et al: Dependence of the utilization of a phenylalanine free amino acid
mixture on different amounts of a single dose ingested. A case report. Eur J Pediatr 1994;153:501-503.
17. Hillman L, Schlotzhauer C, Lee D, et al: Decreased bone mineralization in children with phenylketonuria under
treatment. Eur J Pediatr 1996;155 (Suppl 1):S148-S152.
18. Howard BJ: Discipline in early childhood. Pediatr Clin North Am 1991;38:1351-1369.
19. Kelly RJ: Inborn errors of cholesterol biosynthesis. Adv Pediatr 2000;47:1-53.
20. Kindt E, Motzfeldt K, Halvorsen S, Lie S: Protein requirements in infants and children treated for phenylketonuria.
Am J Clin Nutr 1983;37:778-785.
21. Macht J: Poor Eaters: Helping Children Who Refuse to Eat. New York: Plenum Press, 1990.
22. Monsen ER: Dietary reference intakes for antioxidant nutrients: Vitamin C, vitamin E, selenium, and carotenoids.
23. Pratt EL, Snyderman SE, Cheung MW, et al: The threonine requirement of the normal infant. J Nutr
1955;56:231-251.
24. Preparation of Formula for Infants: Guidelines for Health Care Facilities. Chicago, IL: The American Dietetic
Association, 1991.
25. Scaglioni S, Zucotti G, Vedovello M, et al: Study of serum ferritin in 58 children with classic phenylketonuria and
persistent hyperphenylalaninemia. J Inher Metab Dis 1985;8:160.
26. Schiffman SS, et al: Increased taste thresholds of amino acids with age. Am J Clin Nutr 1979;32:1622.
27. Schoeffer A, Herrmann ME, Broesicke HG, Moench E: Effect of dosage and timing of amino acid mixtures on
nitrogen retention in patients with phenylketonuria. J Nutr Med 1994;4:415-418.
28. Taylor JF, Latta RS: Why Can't I Eat That? Saratoga, CA: R & E Publishers, 1993.
29. Touati G, Rusthoven E, Depondt E, et al: Dietary therapy in two patients with a mild form of sulphite oxidase
deficiency. Evidence for clinical and biological improvement. J Inher Metab Dis 2000;23:45-53.
30. Verkerk PH, van Spronsen FJ, Smit GPA, Sengers RCA: Impaired prenatal and postnatal growth in Dutch patients
with phenylketonuria. Arch Dis Child 1994;71:114-118.
© 2001 Ross Products Division xvii

PROTOCOL 1 — Phenylketonuria (PKU)
Nutrition Support of Infants, Children, and Adults With

PHENEX™-1 and PHENEX™-2 Amino Acid-Modified Medical Foods
I. Introduction
Phenylketonuria (PKU) and hyperphenylalaninemia result from a defect in the enzyme phenylalanine
(PHE) hydroxylase (PAH), which is responsible for changing PHE, an essential amino acid, to tyrosine
(TYR), normally a nonessential amino acid (Figure A) (19, 58). A defect in PAH activity results in
accumulation of PHE in blood and body tissues from which PHE metabolites are produced. Another
consequence is that blood and tissue concentrations of TYR may be deficient since TYR is an
essential amino acid for patients with PKU. Hyperphenylalaninemia may also result from deficiency of
tetrahydrobiopterin (H4 biopterin), a coenzyme for PAH, TYR hydroxylase, and tryptophan
hydroxylase. The latter two enzymes are required for neurotransmitter synthesis. Therapy of H4
biopterin deficiency requires L-DOPA, carbidopa, and H4 biopterin in addition to a PHE-restricted diet
(19, 58). Some patients with hyperphenylalaninemia may have a mutant PAH enzyme with decreased
affinity for the coenzyme H4 biopterin (treat with H4 biopterin, 5-10 mg/kg) (42, 66).
GTP
GTP cyclohydrolase
Dihydroneopterin triphosphate
+ +
NAD NADH + H
Dihydrobiopterin Dihydropteridine reductase

synthetase
(N)
Dietary protein
Dietary protein H4 biopterin H2 biopterin

Tissue protein
CO2 + H2O
Tissue Tyrosine (N)
Phenylalanine*
protein (N) Melanin
(N)
Epinephrine
Phenylalanine Thyroxine
O2 H2O
hydroxylase
Orthohydroxy- Phenylpyruvate* Phenylethylamine

phenylacetate
* Accumulates in untreated PKU
(N) = several steps

Phenyllactate* Phenylacetate*
Indicates sites of possible enzyme defects
Phenylacetylglutamine
Figure A. Phenylalanine metabolism in phenylketonuria
© 2001 Ross Products Division Phenylketonuria 1

II. Screening for PKU
Newborn screening for PKU started in the mid-1960s. An elevated blood PHE concentration found on a
newborn screen suggests the need for a diagnostic work-up. A positive newborn screen for elevated
blood PHE concentration is NOT a positive diagnosis (19, 58).
The incidence of PKU is approximately 1/10,000 to 1/25,000 live births. It is greater in people of Irish
descent than in many other ethnic groups, but PKU is found in all ethnic groups (19, 58).
III. Outcome of Nutrition Support

If untreated, persons with PKU may have irreversible mental retardation and one or more of the
following: neurologic abnormalities, abnormal electroencephalograms (EEGs), seizures, hyperactivity,
musty odor, and eczema. Newborn screening, retrieval, diagnosis, and early nutrition intervention
have resulted in children with normal intelligence. Many treated patients complete college (19, 58).
Until recently, children with PKU were removed from a PHE-restricted diet at school age or younger.
Because brain growth was believed to be complete, a PHE-restricted diet was thought to be no longer
necessary. But data have shown that children removed from a PHE-restricted diet have decreased IQ
and poorer school performance compared to the same age-matched children with PKU who remained
on diet (12). Neurologic deterioration, mental aberrations, physical changes in the brain, and
psychiatric problems have been reported in persons either removed from the PHE-restricted diet or in
poor metabolic control (56, 68, 70, 71). For these reasons, it is now recommended that persons with
PKU remain on diet for life and remain in good metabolic control.
Offspring of mothers with untreated PKU or hyperphenylalaninemia (increased blood PHE without
phenylketones in the urine) suffer from permanent mental retardation and may have microcephaly,
congenital heart defects, and other anomalies. Although these offspring usually do not have PKU, they
are exposed in utero to toxic concentrations of PHE (58).
IV. Establish Diagnosis

A. The Defect (19, 58)
1. PKU may result from defect in any of at least 3 enzymes:
a. Biopterin synthetase group of enzymes.
b. Dihydropteridine reductase.
c. PAH.
d. PAH with decreased affinity for H4 biopterin (42, 66)
B. Clinical Evaluation
1. Concentration of ≥ 2 mg PHE/dL by bacterial inhibition assay of dried blood spot if test is
administered before neonate is 24 hours old (18), or ≥ 4 mg/dL after 24 hours, requires
differential diagnosis.
C. Differential Diagnosis (19, 58)
1. Differential diagnosis will reveal false-positives and identify specific enzyme defect.
2. Therapy depends on enzyme defect present.
3. This protocol addresses nutrition support of patients with PAH deficiency.
V. Rationale for Nutrition Support

A. Correct Primary Imbalance in Metabolic Relationships
1. Restrict dietary PHE to amount tolerated by patient to maintain treatment plasma PHE
concentration.
B. Supply Product of Blocked Primary Pathway
1. Supplement dietary TYR as necessary to maintain normal plasma TYR concentration.
VI. Establish Goals of Nutrition Support (19, 58)

A. Plasma PHE Concentration
1. Maintain 2- to 4-hour postprandial plasma PHE concentration between 2 and 5 mg/dL when
measured by bacterial inhibition assay (120 and 300 µmol/L when measured by quantitative
methods) (19, 46, 47, 63, 64).
a. In patients >10 years of age until adulthood, plasma PHE concentration may range
between 2 and 8 mg/dL (120 - 485 µmol/L) (63, 64).
2 Phenylketonuria © 2001 Ross Products Division
b. For adults with PKU, maintain 2- to 4-hour postprandial plasma PHE concentration
between 2 and 10 mg/dL (120 - 605 µmol/L) (75), although normal concentration was
required in a patient to prevent complications (73).
2. In practice, obtaining blood 2 to 4 hours postprandially is not always possible. Acceptable local
standards should be developed if plasma amino acids are evaluated at other times (Practical
Aspects of Nutrition Support, p viii).
Warning: Blood/plasma PHE concentration must be evaluated once or twice weekly,
with concentrations maintained between 2 and 5 mg/dL. Otherwise, PHE
deficiency may occur. PHE deficiency may result in failure to thrive and
mental retardation (33, 37, 64).
B. Plasma TYR Concentration
1. Maintain 2- to 4-hour postprandial plasma TYR concentration between 50 and 100 µmol/L
(0.9-1.8 mg/dL), or within normal range for age established by laboratory used.
C. Growth, Development, and Nutrition Status
1. Support normal growth rate in infants and children and maintain appropriate weight for height
in adults (3, 5, 7).
2. Support normal development (12, 24, 25, 63, 64).
3. Maintain normal nutrition status (2, 6-8, 16, 23, 28, 29, 33, 51, 53, 54, 57).
4. Prevent catabolism.
D. Behavior, Mental Development, and Neurologic Status
1. Prevent behavioral abnormalities (10, 63, 64, 71).
2. Improve behavior of previously untreated adults with PKU (10, 73, 75).
3. Prevent EEG changes and neurologic deterioration in adults (20, 68, 70).
E. Physical Manifestations
1. Prevent osteopenia (17, 36), eczema and offensive body odor (56).
VII. Establish Prescription

A. PHE
1. Prescribe PHE intake that promotes goals of nutrition support (Table 1-1, p 12).
2. PHE requirements vary widely:
a. From patient to patient, depending on activity of PAH, which is dependent on genotype
(1, 3, 4, 30, 31, 69).
b. In same patient, depending on:
1) Age.
2) Growth rate (41).
3) Adequacy of energy and protein intakes (39).
4) State of health.
3. If diagnostic plasma PHE concentration is in following ranges, delete PHE from diet for hours
noted:
Diagnostic Plasma PHE Delete Dietary PHE For:
(µmol/L) (mg/dL) (Hours)
240 < 605 4 < 10 24
605 < 1,210 10 < 20 48
1,210 < 2,420 20 < 40 72
≥ 2,420 > 40 96
a. To prevent PHE deficiency, plasma PHE concentration must be analyzed daily when
all PHE is deleted from diet.
b. When plasma PHE concentration reaches upper limit of treatment range
(300 µmol/L), PHE must be added to diet.
4. Dietary PHE suggested for initiating therapy after 1 to 4 days of PHE-free medical food
mixture depends on maximum diagnostic quantitative plasma PHE concentration (not by
bacterial inhibition assay). See values noted below for amounts of dietary PHE to begin
therapy for specific plasma PHE concentrations:

Plasma PHE Dietary PHE
(µmol/L) (mg/dL) (mg/kg)
≤ 605 ≤ 10 70
> 605 to ≤ 1210 > 10 to ≤ 20 55
> 1210 to ≤ 1815 > 20 to ≤ 30 45
> 1815 to ≤ 2420 > 30 to ≤ 40 35
> 2420 > 40 25
5. Frequent monitoring of plasma PHE concentration is essential to assess patient's changing
requirements.
a. The closer to normal range that plasma PHE concentration is maintained, the more
frequently plasma PHE concentration must be evaluated to prevent deficiency.
b. See Section X, Suggested Evaluation of Nutrition Support, p 7.
6. Between 3 and 5 months of age, PHE requirements per kg body weight may decrease
considerably.
Warning: PHE deficiency results in following adverse effects:
Low or elevated plasma PHE concentration, depending on stage of PHE
deficiency (19).
Bone changes and decreased growth rate in infants and children and weight
loss in adults (21, 36, 40, 60).
Changes in red blood cell precursors and anemia (53, 54).
Generalized aminoaciduria and hypoproteinemia (37).
Mental retardation (33, 64).
Hair loss.
Low plasma transthyretin (11).
B. TYR (46)
1. Prescribe TYR intake that maintains treatment plasma TYR concentration.
2. Lowest value for dietary TYR for each age group listed in Table 1-1, p 12, is suggested to start
therapy.
3. Changing requirements of patients are determined only by frequent monitoring of plasma TYR
concentration.
a. Prescribe TYR above amount supplied by Phenex and beikost or table foods only if
plasma TYR concentration is below normal.
C. Protein
1. Prescribe, initially, amount greater than Recommended Dietary Allowances (RDAs) (5, 22, 35,
41, 46, 55, 62) (Table 1-1, p 12). For neonates, use 3.50 g/kg/day.
2. Requirements are greater than RDAs when L-amino acids supply majority of protein
equivalent as result of:
a. Rapid amino acid absorption (26, 27).
b. Early and high peak of plasma amino acid concentrations after ingestion of meals where
large part of protein is supplied by L-amino acids (26, 27).
c. Rapid catabolism of amino acids (35, 38).
d. Possible decreased total amino acid absorption (48).
Warning: Long-term inadequate protein intake will result in failure to thrive in infants,
poor growth in children, weight loss in adults, low plasma transthyretin
concentrations, osteopenia, hair loss, and decreased PHE tolerance.
D. Energy (9)
1. Prescribe amount that should support normal weight gain in infants and children and maintain
appropriate weight for height in adults (Table 1-1, p 12).
2. Requirements vary widely and may be greater than normal when L-amino acids supply
majority of protein equivalent (50, 52)
3. Hyperactivity, if present, may significantly increase needs.

Warning: Inadequate energy intake will result in failure to thrive in infants, poor growth
in children, weight loss in adults, and low plasma transthyretin concentration.
Weight loss will result in elevated plasma PHE concentration as result of
protein catabolism. Poor growth will result in lower than expected tolerance
of PHE.
E. Fluid
1. Prescribe amount that will supply water requirements (Table 1-1, p 12). Under normal
circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to children and adults
for each kcal ingested.
2. Requirements may be higher than recommended secondary to increased fluid loss with fever.
VIII. Fill Prescription

A. PHE
1. Calculate amount of infant formula with iron, human milk, beikost, or table foods (Table 1-2,
p 12) required to fill PHE prescription.
a. Low-iron infant formula, whole cow's milk, and evaporated milk should not be used as
PHE source for infants because of low iron content.
2. Measure liquid infant formula, human milk, and whole cow's milk with disposable syringe.
Weigh powdered infant formula on scale that reads in grams.
a. For other approaches to using human milk, see reference 76.
3. Add beikost (table foods) (Table 1-2, p 12) to gradually displace PHE provided by infant
formula or human milk after infant is 3 to 4 months old or is developmentally ready.
4. Parents or patients may select any food in prescribed food lists (Table 1-3, p 13) in specified
amounts to fill diet prescription.
B. Protein
1. Calculate amount of infant formula with iron, human milk, beikost, whole cow's milk, or table
foods (Table 1-2, p 12) required to fill the PHE prescription.
2. Subtract amount determined above from total protein prescription.
3. Supply any remaining prescribed protein with Phenex (Table 1-4, p 27).
a. Phenex-1 is for infants and toddlers and Phenex-2 is for children, adolescents, and adults,
but may be used by toddlers if child's appetite is small.
b. Weigh Phenex powder on scale that reads in grams because of variability of household
measuring equipment (Practical Approaches to Nutrition Support, p vii) and changes in
density during shipping.
c. See Table 1-4 (p 27, footnote 3) for approximate packed weight of Phenex powder in
level, dry US standard household measures.
C. TYR
1. Calculate approximate amount of TYR provided by infant formula with iron, human milk,
beikost, whole cow's milk, or table foods (Table 1-2, p 12) required to fill PHE prescription.
2. Calculate amount of TYR supplied by Phenex (Table 1-4, p 27) required to fill protein
prescription.
3. Added together, values calculated above should fall within range of TYR intake recommended
in Table 1-1, p 12.
4. Supply remaining prescribed TYR as pure suspension. Add supplemental L-TYR only if
plasma TYR concentration is below normal.
a. For infants, mix weighed amounts of L-TYR powder with boiled, cooled water to yield
0.5 mg/mL (eg, 500 mg of L-TYR with enough water to yield 1 liter).
b. Refrigerate suspension in sterilized, closed container until used. Discard unused
suspension after 1 week, if not frozen.
c. Shake well before using. Measure L-TYR (Appendix 26, p A-28) suspension into medical
food mixture with disposable syringe.
5. For children or adults, L-TYR powder may be mixed with fruit purées such as applesauce,
soups, puréed vegetables, and mashed potatoes.

6. L-TYR tablets may be used if patient can swallow them. Tablets are available at some
pharmacies.
D. Energy
1. Calculate energy provided by infant formula with iron, human milk, beikost, whole cow's milk,
or table foods (Table 1-2, p 12) and Phenex (Table 1-4, p 27) required to fill PHE and protein
prescriptions.
2. Subtract amount determined above from total energy prescription.
3. Provide remaining prescribed energy with Polycose ® Glucose Polymers powder
(23 kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9); Pro-Phree ® Protein-Free
Energy Module With Iron, Vitamins & Minerals (Appendix 11, p A-10); sugar (48 kcal/Tbsp); or
Free Foods B (Table 1-2, p 12), depending on age of patient.
a. Do not use corn syrup or table sugar for infants because of osmolarity they yield (45).
b. Do not use honey for infants because it may contain botulinum toxin (67).
E. Fluid and Mixing Instructions
1. Add sufficient boiled, cooled water to infant formula or human milk, Phenex, carbohydrate,
and L-TYR (if needed) to yield prescribed volume. Tap water may replace boiled, cooled
water when preparing Phenex for older infants, children, and adults.
2. Mix with sterilized blender at lowest speed for no longer than 3 to 4 seconds. Excess mixing
may destabilize emulsion. Medical food may also be mixed in sterilized, tightly closed
container by shaking vigorously for 10 to 12 seconds.
3. Refrigerate in sterilized, closed containers until used. Discard unused portion 24 hours after
mixing because of nutrient loss. Store unopened cans at room temperature. Cover opened
can and store in refrigerator. Use within 1 month after opening.
4. Do not use terminal sterilization or boil because of Maillard reaction (Practical Aspects of
Nutrition Support, p viii).
5. Warm or cool medical food mixture to room temperature before feeding to infants. Shake well
before feeding.
6. Do not warm medical food mixture in microwave oven. Unevenly heated formula can burn
infants and steam can make bottles explode.
7. Notify parents or caretakers when they may discontinue using aseptic technique in preparing
medical food mixture for infants.
8. For children and adults, chill Phenex medical food mixture to improve taste.
F. Diet Guide
1. Provide parents, caretakers, or patient with completed Diet Guide (Appendix 22, p A-24) with
each diet change.
2. Feed young infants 6 to 8 times daily (35, 55).
3. Feed older infants, children, and adults 4 to 6 times daily (35, 55).
IX. Evaluate Adequacy and Safety of Planned Nutrition Support

A. Nutrient Adequacy
1. Determine if diet provides nutrients in amounts prescribed in Section VII, Establish
Prescription, p 3.
a. See Table 1-4, p 27, for composition of Phenex and Table 1-2, p 12, for nutrient
composition of infant formulas, human milk, and whole cow's milk.
b. See Appendix 9, p A-9, for composition of Polycose and Appendix 11, p A-10, for
composition of Pro-Phree.
2. Check diet to determine if it supplies Recommended Dietary Intakes (RDIs) for minerals and
vitamins (Appendices 4 through 8, 13, and 14, pp A-4 through A-8, A-14, and A-15).
a. Appendix 23, p A-25, may be used to check adequacy of nutrients if computer program is
not available.
b. If Phenex mixture provides < 100% of RDIs for infants and < 75% of RDIs for children and
adults, supplement diet with needed minerals and vitamins if not provided by beikost or
table foods and laboratory tests indicate need (Appendix 11, p A-10, for composition of
supplements).
B. Osmolarity
1. If concentration of prescribed medical food mixture is > 24 kcal/fl oz, determine if osmolarity
is in acceptable range.
a. Determine osmolarity by laboratory analysis or use mathematical formula given in
Appendix 18, p A-20.
b. Osmolarity per gram of Phenex is listed in Appendix 19, p A-21.
2. If osmolarity is > 450 mosm/L for neonates, > 750 mosm/L for children, > 1,000 mosm/L for
adults (62), or greater than tolerated by patient, increase water content of prescribed medical
food mixture and recalculate its osmolarity (44, 65).
C. Potential Renal Solute Load
1. Dehydration will result if renal solute load is greater than renal-concentrating ability of patient.
2. If concentration of medical food mixture prescribed is > 24 kcal/fl oz, estimate its potential
renal solute load.
a. This step is important to prevent dehydration of infants who may have renal-concentrating
capacity as low as 600 mosm/L.
b. Upper limit of renal solute load for neonates is approximately 1,100 mosm/L (61).
3. A method for estimating potential renal solute load is given in Appendix 20, p A-22.
4. If potential renal solute load is excessive, increase water content of medical food mixture and
recalculate.
X. Suggested Evaluation of Nutrition Support

A. Plasma PHE and TYR Concentrations (46, 64)
1. Initial.
a. Evaluate twice weekly by quantitative methods until plasma concentrations stabilize and
approximate dietary PHE and TYR requirements are known.
2. Ongoing.
a. Frequent evaluations help ensure adherence to nutrition support plan.
b. Evaluate plasma PHE concentration weekly by bacterial inhibition assay or fluorometric
method.
c. Evaluate plasma PHE and TYR concentrations monthly by quantitative methods.
3. Unacceptable PHE concentrations.
a. If plasma PHE concentration is not detected and patient has ingested full prescription:
1) Add 50 mg to prescribed PHE and reevaluate plasma PHE concentration in 3 days.
2) If plasma PHE concentration continues undetected, repeat above process until value
is in treatment range.
b. If plasma PHE concentration is < 120 µmol/L (2 mg/dL) and patient has ingested full
prescription:
1) Add 15 mg to prescribed PHE and reevaluate plasma PHE concentration in 3 days.
2) If plasma PHE concentration continues < 120 µmol/L (2 mg/dL), repeat above process
until value is in treatment range.
c. If plasma PHE concentration is > 300 µmol/L (5 mg/dL) and < 605 µmol/L (10 mg/dL) and
patient is not ill and has not ingested more PHE or significantly less protein and energy
than prescribed:
1) Subtract 15 mg from prescribed PHE and reevaluate plasma PHE concentration in
3 days.
2) If plasma PHE concentration continues > 300 µmol/L (5 mg/dL), repeat above process
d. If plasma PHE concentration is > 605 µmol/L (10 mg/dL) and patient is not ill and has not
ingested more PHE or significantly less protein and energy than prescribed:
1) Subtract 30 mg from prescribed PHE and reevaluate plasma PHE concentration in
3 days.
2) If plasma PHE concentration continues > 605 µmol/L (10 mg/dL), repeat above
process until value is in treatment range.

B. Protein Status
1. Evaluate plasma transthyretin concentration every 3 months until patient is 1 year of age and
every 6 months thereafter (Appendix 17, p A-18, for standards).
a. Plasma transthyretin concentrations provide a more reliable and rapid indication of protein
status than plasma albumin concentrations.
b. Plasma albumin concentrations may be in the normal range when plasma transthyretin
concentrations show a clear deficiency (11).
2. If plasma transthyretin concentration is below standard:
a. Increase prescribed protein by 5% to 10% and reevaluate plasma transthyretin
concentration in 1 month. If plasma PHE concentration is in treatment range, use Phenex
to increase protein.
b. If plasma transthyretin concentration continues below standard, repeat above process until
value is in normal range.
C. Iron Status
1. Plasma ferritin concentration (13-15).
a. Evaluate at 6, 9, and 12 months of age and every 6 months thereafter (Appendix 17,
p A-18, for standards).
b. If plasma ferritin concentration is below standard:
1) Increase iron intake to 4 mg/kg with supplements (ferrous sulfate).
2) Evaluate plasma ferritin concentration monthly on increased iron intake.
3) Continue iron supplements until plasma ferritin concentration is in normal range.
2. Complete blood count.
a. Hemoglobin and hematocrit concentrations should be evaluated at 6, 9, and 12 months of
age and every 6 months thereafter (Appendix 17, p A-18, for standards).
D. Serum/Erythrocyte Vitamin B12 and Folate
1. Patients who routinely fail to ingest prescribed amounts of medical food are at risk of
vitamin B12 and folate deficiencies (32).
2. Serum or erythrocyte vitamin B12 and folate should be routinely analyzed if medical food
prescribed is not ingested.
3. Serum and erythrocyte concentrations should be maintained between the following values:
Tissue Vitamin B12 (74) Folate (34)
Serum > 300 pg/mL > 5 to < 10 ng/mL
Erythrocyte --- > 200 to < 300 ng/mL
4. Both vitamin B12 and folate tablets should be administered daily if the patient will not ingest
prescribed amounts of medical food.
E. Growth Status
1. Length/height and weight.
a. Measure monthly to 1 year, every 3 months to 4 years, and every 6 months thereafter.
Plot measurements on NCHS growth charts.
b. Maintain length/height and weight between 10th and 90th percentiles. Some normal
infants, children, and adults will fall above or below these percentiles.
2. If length/height or weight falls below usual growth channel:
a. Increase prescribed protein and energy by 5% to 10% and remeasure in 1 month.
b. If length/height or weight remains low, repeat above process until usual growth channel is
achieved.
3. For previously untreated adult with PKU, weigh weekly after diet is initiated until weight is
stabilized at appropriate weight for height, then weigh monthly.
a. Liberal use of very-low-protein foods, Free Foods A (p 24), and Free Foods B (p 25) will
help minimize weight loss.
F. Nutrient Intake
1. Maintain records of food intake for 3 days immediately before each blood test (Appendices 24
and 25, pp A-26 and A-27).

2. For previously untreated adult with PKU who lives in an institution or group home that uses
cycle menus, actual amounts of foods eaten should be noted in medical record.
3. Previously untreated adults with PKU who live independently will require help with grocery
shopping, meal planning, cooking, and record keeping (75). They should be taught to use
pictures or models of food to help them keep food diaries if they are illiterate, or if their
guardian cannot maintain records.
4. Evaluate intakes of PHE, TYR, protein, and energy before each blood test.
5. Evaluate mineral and vitamin intakes after each diet change.
not available.
b. See Appendix 28, p A-29, for information about ordering software for diet evaluation.
G. Clinical Summary
1. A summary record of growth, laboratory, and nutrient intake data is useful for patient
management (Table 1-5, p 29).
XI. Sample Prescriptions

A. Example 1
Establish and fill prescription for newborn weighing 3.3 kg who has diagnostic plasma PHE
concentration of 1510 µmol/L (41 mg/dL) using Recommended Daily Nutrient Intakes from
Table 1-1, p 12, and average nutrient contents from Tables 1-2 and 1-4, pp 12 and 27.
1. Establish prescription.
PHE 45 mg/kg x 3.3 kg = 148 mg/day
TYR 350 mg/kg x 3.3 kg = 1,155 mg
Protein 3.5 g/kg x 3.3 kg = 11.5 g
Energy 127 kcal/kg x 3.3 kg = 420 kcal
Fluid 160 mL/kg x 3.3 kg = 528 mL
2. Fill prescription.
Medical Food Mixture Measure PHE TYR Protein Energy
(mg) (mg) (g) (kcal)
Phenex-1 54 g 0 810 8.1 259
Similac With Iron RTF 251 mL 148 146 3.5 171
L-Tyrosine 199 mg 0 199 0.0 0
Add water to make 530 mL (18 fl oz).
Total per day 148 1,155 11.6 430
Total per kg 45 350 3.5 130
Approximate osmolarity of medical food mixture is < 450 mosm/L. Estimated potential renal solute
load is < 160 mosm.
B. Example 2
Establish and fill prescription for 2-year-old child weighing 13 kg using Recommended Daily
Nutrient Intakes from Table 1-1, p 12, and Average nutrient contents from Tables 1-2 and 1-4,
pp 12 and 27.
PHE 200 mg/day
TYR 3,000 mg
Protein 30 g
Energy 1,300 kcal
Fluid 1,375 mL

Phenex-1 164 g 0 2,460 24.6 787
L-Tyrosine 402 mg 0 402 0.0 0
Sugar 8 g (2 tsp) 0 0 0.0 32
Add water to make 710 mL (24 fl oz). Offer additional fluid ad libitum daily.
Food List Servings

Breads/Cereals 3 90 60 1.8 90
Fats 2 10 8 0.2 120
Fruits 2 30 20 1.0 120
Vegetables 5 75 50 2.5 50
Free Foods B 2 0 0 0.0 110
Total per day 205 3,000 30.1 1,309
Approximate osmolarity of medical food mixture is < 700 mosm/L.
C. Example 3
Establish and fill prescription for 6-year-old child using Recommended Daily Nutrient Intakes from
Table 1-1, p 12, and average nutrient contents from Tables 1-2 and 1-4, pp 12 and 27.
PHE 235 mg/day
TYR 3,500 mg
Protein 35.0 g
Energy 1,700 kcal
Fluid 1,700 mL
Medical Food Measure PHE TYR Protein Energy
Mixture (mg) (mg) (g) (kcal)
Phenex-2 97 g 0 2,910 29.1 398
L-Tyrosine 430 mg 0 430 0.0 0
Sugar 84 g (7 Tbsp) 0 0 0.0 336
Food List Servings

Fats 2 10 8 0.2 120
Fruits 3 45 30 1.5 180
Free Foods A 3 15 12 0.3 195
Free Foods B 6 0 0 0.0 330
Total per day 235 3,500 35.0 1,709
D. Example 4
Establish and fill prescription for 20-year-old woman using Recommended Daily Nutrient Intakes
from Table 1-1, p 12, and average nutrient contents from Tables 1-2 and 1-4, pp 12 and 27.
PHE 220 mg/day
TYR 5,000 mg
Protein 50 g
Energy 2,100 kcal
Fluid 2,100 mL

Medical Food Measure PHE TYR Protein Energy
Mixture (mg) (mg) (g) (kcal)
Phenex-2 149 g 0 4,470 44.7 611
L-Tyrosine 376 mg 0 376 0.0 0
Sugar 60 g (5 Tbsp) 0 0 0.0 240
Food List Servings

Fats 3 15 12 0.3 180
Fruits 3 45 30 1.5 180
Free Foods A 3 15 12 0.3 195
Free Foods B 10 0 0 0.0 550
Total per day 225 5,000 50.2 2,096
XII. Nutrition Support During Febrile Illness or Following Trauma

A. Rationale
1. In normal persons, febrile illness and trauma are accompanied by catabolism of body
protein (72).
2. Well-nourished patients with PKU respond to infection and trauma as do normal persons.
3. Extent of protein catabolism determines subsequent elevation in plasma PHE concentration.
B. Objectives of Nutrition Support
1. Maintain hydration and electrolyte balance.
a. Offer infants and toddlers Pedialyte ® Oral Electrolyte Maintenance Solution ad libitum
(Appendix 9, p A-9).
2. Depress catabolism.
a. Enhance energy intake when possible by offering fruit juices ad libitum as tolerated, liquid
Jell-O ®, Polycose powder or liquid (Appendix 9, p A-9), or Pro-Phree (Appendix 11, p A-
10) added to fruit juices or Pedialyte if tolerated and caffeine-free soft drinks (not diet
drinks).
1) 1/3 cup of Polycose powder may be added to liquid Pedialyte to yield 8 fl oz.
b. Return patient to Phenex medical food mixture and pre-illness diet as rapidly as possible.
1) Begin with 1/2 original strength of Phenex medical food mixture.
2) Increase to original strength as tolerated.
C. Parenteral Nutrition
1. If parenteral amino acid solutions are indicated, see Appendix 26, p A-28.

TABLE 1-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With PKU
Age Nutrient
1-3 1
PHE TYR Protein4 Energy4 Fluid5
(mg/kg) (mg/kg) (g/kg) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 25 - 70 300 - 350 3.50 - 3.00 120 (145 - 95) 160 - 135
3 to < 6 mo 20 - 45 300 - 350 3.50 - 3.00 120 (145 - 95) 160 - 130
6 to < 9 mo 15 - 35 250 - 300 3.00 - 2.50 110 (135 - 80) 145 - 125
9 to < 12 mo 10 - 35 250 - 300 3.00 - 2.50 105 (135 - 80) 135 - 120
(mg/day) (g/day) (g/day) (kcal/day) (mL/day)
Girls and Boys
1 to < 4 yr 200 - 400 1.72 - 3.00 ≥ 30 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 210 - 450 2.25 - 3.50 ≥ 35 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 220 - 500 2.55 - 4.00 ≥ 40 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 250 - 750 3.45 - 5.00 ≥ 50 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 230 - 700 3.45 - 5.00 ≥ 55 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr 220 - 700 3.75 - 5.00 ≥ 60 2,100 (1400 - 2500) 2,100 - 2,500
Men
11 to < 15 yr 225 - 900 3.38 - 5.50 ≥ 55 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 295 - 1,100 4.42 - 6.50 ≥ 65 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr 290 - 1,200 4.35 - 6.50 ≥ 70 2,900 (2000 - 3300) 2,000 - 3,300
1
See Section VII, Establish Prescription, p 3, for initial dietary PHE to prescribe based on diagnostic plasma PHE.
Modify prescription based on frequently obtained blood and/or plasma values and growth in infants and children and
frequently obtained plasma values and weight maintenance in adults.
2
PHE requirements of premature infants may be greater than highest value noted (59).
3
Modified from references 1, 3-5, 19, 43.
4
Modified from reference 22.
5
Modified from reference 13. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to
children and adults for each kcal ingested.
TABLE 1-2. Serving Lists for PHE-Restricted Diets: Average Nutrient Content per Serving1
Food List Nutrient

PHE TYR Protein Energy
Breads/Cereals 30 20 0.6 30
Fats 5 4 0.1 60
Fruits 15 10 0.5 60
Vegetables 15 10 0.5 10
Free Foods A 5 4 0.1 65
Free Foods B 0 0 0.0 55
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed , 100 mL 86 29 1.86 68
2
Human Milk, 100 mL, 3 48 55 1.07 72

Isomil ® Soy Formula With Iron, Ready to Feed, 100 mL 2 88 60 1.66 68
2
Similac ® With Iron Infant Formula, Ready to Feed, 100 mL 59 58 1.40 68
3
Whole cow's milk, 100 mL 164 164 3.39 63
1
From reference 19.
2
See Appendices 4 through 7, pp A-4 to A-7, for complete nutrient composition of infant formulas.
3
From reference 49. See Appendix 8, p A-8, for complete nutrient composition.

TABLE 1-3. Serving Lists for PHE-Restricted Diets: Gerber ® Baby Food (Beikost)
Food Weight Approximate PHE TYR Protein Energy

(g) Measure (mg) (mg) (g) (kcal)
For greatest accuracy, weigh food on scale that reads in grams. All measures are level.
BREADS AND CEREALS
Baked Finger Snacks, Graduates

Animal crackers, cinnamon graham 10 1-1/2 cracker 29 10 0.6 45
Apple cinnamon cookies 10 1 cookie 31 12 0.8 43
Banana cookies 10 1-1/4 cookie 30 11 0.7 43
Strawberry fruit bars 12 1-1/3 bar 31 12 0.6 49
Veggie crackers 7 10 crackers 30 10 0.6 33
Cereals, Dry
Barley 4 1 Tbsp + 1/4 tsp 28 15 0.5 15
Mixed 6 1 Tbsp + 2 tsp 30 15 0.6 23
Oatmeal 3 3/4 Tbsp 27 14 0.4 12
Oatmeal/banana 4 1 Tbsp + 1/4 tsp 27 17 0.4 16
Oatmeal/mixed fruit 6 1 Tbsp + 2 tsp 32 17 0.6 25
Rice 6 1 Tbsp + 2 tsp 28 16 0.5 23
Rice/apples 11 3 Tbsp 30 21 0.6 43
Rice/apple bits 8 2 Tbsp + 1/2 tsp 29 15 0.6 32
Rice/bananas 9 2 Tbsp + 1-1/2 tsp 30 19 0.6 35
Rice/mixed fruit 9 2 Tbsp + 1-1/2 tsp 31 23 0.6 35
Cereals, Jarred
1st Foods ®
Oatmeal 34 2 Tbsp + 1 tsp 30 20 0.6 19
2nd Foods ®
Mixed/applesauce/bananas 57 1/4 cup 30 15 0.6 49
Oatmeal/applesauce/bananas 42 3 Tbsp 30 13 0.5 35
Rice/applesauce 57 1/4 cup 30 15 0.4 52
3rd Foods ®
Mixed/apples/bananas 54 3 Tbsp + 2 tsp 30 16 0.6 41
Oatmeal/apples/cinnamon 53 3 Tbsp + 2 tsp 30 16 0.6 36
Tender Harvest ™
Greenbeans/potatoes 26 ND 30 23 0.6 16
Spring garden vegetables 60 ND 30 18 0.9 21
Vegetables
1st Foods ®
Peas 24 1 Tbsp + 2 tsp 30 19 0.7 12
Potatoes 75 5 Tbsp + 1 tsp 30 25 0.8 35
Sweet potatoes 45 3 Tbsp 30 12 0.5 29
2nd Foods ®
Creamed corn 31 2 Tbsp 30 20 0.6 19
Creamed spinach 20 1 Tbsp + 1-1/2 tsp 30 23 0.6 9
Garden vegetables 30 2 Tbsp 30 18 0.4 11
Peas 24 1 Tbsp + 2 tsp 30 19 0.7 12
Sweet potatoes 48 3 Tbsp + 1 tsp 30 12 0.5 30
3rd Foods ®
Peas/rice 23 1 Tbsp + 2 tsp 30 15 0.2 12
FRUITS/JUICES
Mixed fruit juice 125 4 fl oz 15 6 0.3 60

Pear juice 202 6 2/5 fl oz 15 4 0.6 99
1st Foods ®
Bananas 47 3 Tbsp + 3/4 tsp 15 8 0.5 47

Peaches 88 6 Tbsp + 1/2 tsp 15 9 0.6 38
Pears 68 1/4 cup + 2 tsp 15 4 0.3 39
Prunes 58 1/4 cup 15 5 0.6 58
2nd and 3rd Foods ®
Applesauce/apricot 100 7 Tbsp 15 6 0.3 52
Apricots/mixed fruit 75 5 Tbsp + 1 tsp 15 7 0.4 45
Bananas 47 3 Tbsp + 3/4 tsp 15 8 0.5 42
Bananas/apples/pears 43 3 Tbsp 15 5 0.4 36
Banana/pineapple 43 3 Tbsp 15 6 0.4 32
Banana/strawberry 60 1/4 cup 15 8 0.6 54
Hawaiian delight dessert, 2nd Foods ® 24 1 Tbsp + 2 tsp 15 9 0.3 20
Hawaiian delight dessert, 3rd Foods ® 21 1 Tbsp + 1-1/2 tsp 15 8 0.3 18
Peach cobbler dessert, 2nd Foods ® 136 9 Tbsp + 1-1/2 tsp 15 7 0.7 103
Peach cobbler dessert, 3rd Foods ® 125 1/2 cup + 2 tsp 14 4 0.6 54
Peaches, 2nd Foods ® 88 6 Tbsp + 1/2 tsp 15 9 0.6 56
Peaches, 3rd Foods ® 83 5 Tbsp + 2 tsp 15 7 0.6 53
Pear/pineapple 71 1/3 cup 15 4 0.3 39
Pears 88 6 Tbsp + 1/2 tsp 15 8 0.4 65
Plums/apples, 2nd Foods ® 94 6 Tbsp + 2 tsp 15 5 0.4 66
Plums/apples, 3rd Foods ® 71 5 Tbsp 15 4 0.3 49
Prunes/apples 71 1/3 cup 15 6 0.4 55
Fruit Dices, Graduates™

Apples 136 ND 15 4 0.3 65
Mixed fruit 115 ND 15 6 0.3 56
Peaches 94 ND 15 6 0.5 46
Pears 136 ND 15 7 0.4 73
Fruit/Vegetable Juices
Apple/carrot 214 6-3/4 fl oz 15 11 0.2 89
Apple/sweet potato 125 4 fl oz 15 9 0.4 62
Tender Harvest™
Apple/sweet potato 125 ND 15 8 0.3 72
Banana/oatmeal/peach 27 ND 15 6 0.3 20
Pear/wild blueberry 100 ND 15 5 0.4 61
Pears/winter squash 25 ND 15 6 0.3 13
Tropical fruit blend 68 ND 15 7 0.4 50
VEGETABLES
1st Foods ®
Carrots 75 5 Tbsp + 1 tsp 15 10 0.7 26
Green beans 23 1 Tbsp + 2 tsp 15 9 0.4 9
Squash 50 3 Tbsp + 1-1/2 tsp 15 14 0.4 17
2nd Foods ®
Carrots 75 5 Tbsp + 1 tsp 15 10 0.6 22
Green beans 31 2 Tbsp 15 11 0.4 10
Mixed vegetables 27 1 Tbsp + 2 tsp 15 11 0.3 11
Squash 33 2 Tbsp + 1 tsp 15 7 0.2 10
3rd Foods ®
Carrots 65 4 Tbsp + 1-1/2 tsp 15 10 0.5 19
Green beans/rice 28 2 Tbsp 15 11 0.3 12
Squash 71 1/3 cup 15 11 0.6 23
Tender Harvest™
Butternut squash/corn 25 ND 15 10 0.5 12
Garden carrots/brown rice 47 ND 15 9 0.4 20

Vegetable Dices, Graduates
Carrots 38 ND 15 8 0.2 9
Green beans 28 ND 15 12 0.3 7
FREE FOODS A
Apple juice 218 7 fl oz 5 5 0.2 109

Apple/banana juice 93 3 fl oz 5 4 0.2 50
Apple/cherry juice 124 4 fl oz 5 3 0.3 62
Apple/cranberry juice 93 3 fl oz 5 4 0.2 46
Apple/grape juice 218 7 fl oz 5 5 0.2 112
Apple/prune juice 124 4 fl oz 5 4 0.3 69
Fruit medley tropical fruit dessert 100 7 Tbsp 5 2 0.2 64
Guava tropical fruit dessert 83 1/3 cup + 2-1/2 tsp 5 2 0.1 58
Mango/banana/passion fruit juice 57 1-3/4 fl oz 6 3 0.1 34
Mango tropical fruit dessert 50 3 Tbsp + 1-1/2 tsp 5 3 0.1 43
Mixed fruit juice 163 5 fl oz 5 2 0.5 80
Orange juice 100 3-1/5 fl oz 7 3 0.6 47
Papaya tropical fruit dessert 83 1/3 cup + 2-1/2 tsp 5 2 0.2 53
Peach/mango dessert 78 1/3 cup + 1 tsp 5 3 0.2 47
1st and 2nd Foods ®
Applesauce 86 1/4 cup + 2 Tbsp 5 3 0.2 48
Apple/blueberry 83 5 Tbsp + 2 tsp 5 3 0.2 42
3rd Foods ®
Fruit salad 50 3 Tbsp + 1-1/2 tsp 5 3 0.2 32
Beverages, Graduates ®
Berry punch 218 7 fl oz 5 5 0.2 111
Fruit punch 218 7 fl oz 5 5 0.2 113
Tender Harvest™
Apple/mango/kiwi 100 7 Tbsp 5 3 0.1 60
Apple/strawberry 100 7 Tbsp 5 3 0.1 60
1
Prepared from 1998 and 1999 data from Gerber Products Co, Fremont, MI 49413.
ND = No data.
Weights and Measures

Except for Dry Cereals and Food Dices, the following weights apply:
Level = Level
1 tsp = 1/3rd Tbsp = 4.8 g
1 Tbsp = 1/16th cup = 14.3 g
1/4 cup = 4 Tbsp = 57.2 g
1/3 cup = 5-1/3rd Tbsp = 76.2 g
1/2 cup = 8 Tbsp = 114.3 g
2/3 cup = 10 2/3rd Tbsp = 152.5 g
3/4 cup = 12 Tbsp = 171.5 g
1 cup = 16 Tbsp = 228.6 g

1
TABLE 1-3. Serving Lists for PHE-Restricted Diets: Table Foods

BREADS AND CEREALS
Cereals, Cooked. Measure after cooking.

Corn grits
instant
cheese flavor 36 1/4 packet 36 29 0.7 27
plain 34 1/4 packet 27 22 0.5 20
regular, quick (plain) 45 3 Tbsp 33 28 0.6 28
Cream of Rice 81 1/3 cup 30 40 0.7 42
Cream of Wheat
instant 30 2 Tbsp 30 18 0.6 19
Mix'n Eat
flavored 38 1/4 packet 33 20 0.6 33
plain 36 1/4 packet 37 22 0.7 26
quick 30 2 Tbsp 25 14 0.4 16
regular 30 2 Tbsp 30 18 0.5 19
Farina 44 3 Tbsp 34 20 0.6 22
Maltex ® 31 2 Tbsp 33 19 0.7 22
Malt-o-Meal ® 35 2 Tbsp + 1 tsp 29 16 0.5 18
Maypo ® Oat 30 2 Tbsp 34 20 0.7 21
Oats, regular, quick, and instant 20 1 Tbsp + 1 tsp 28 18 0.5 12
Pettijohns ® 30 2 Tbsp 24 14 0.5 20
Ralston ® 32 2 Tbsp 32 19 0.7 17
Roman Meal ® (plain) 22 1 Tbsp + 1-1/2 tsp 31 22 0.6 14
Wheatena ® 30 2 Tbsp 29 17 0.6 22
Whole Wheat Hot Natural 30 2 Tbsp 29 17 0.6 19
Cereals, Ready To Eat

All Bran ® 5 1 Tbsp 29 22 0.8 13
Alpha-Bits ® 7 1/4 cup 29 20 0.5 28
Apple Jacks ® 9 1/3 cup 26 18 0.5 36
100% Bran ® 6 1 Tbsp + 1-1/2 tsp 30 22 0.8 17
Bran Buds ® 5 1 Tbsp 28 21 0.7 14
Bran Chex ® 6 2 Tbsp 29 23 0.6 20
Cap'n Crunch ® 12 1/3 cup 33 25 0.6 51
Cap'n Crunch's ® Crunch Berries 12 1/3 cup 32 25 0.6 49
Cap'n Crunch's ® Peanut Butter 9 1/4 cup 33 27 0.6 38
Cheerios ® 4 3 Tbsp 35 23 0.6 17
Cinnamon Toast Crunch ® 19 1/2 cup 30 18 0.7 80
Cocoa Krispies ® 12 1/3 cup 27 34 0.6 46
Cocoa Pebbles ® 16 1/2 cup 33 42 0.8 66
Cocoa Puffs ® 19 2/3 cup 31 26 0.7 73
Cookie Crisp ® 10 1/3 cup 26 19 0.5 39
Corn Bran ® 9 1/4 cup 32 24 0.6 31
Corn Chex ® 7 1/4 cup 26 22 0.5 28
Corn Flakes ® 7 1/3 cup 31 26 0.6 29
Crispy Rice 9 1/3 cup 26 34 0.6 37
Crispy Wheat 'n Raisins ® 11 1/4 cup 35 21 0.7 37
C W Post ®
plain 6 1 Tbsp 29 21 0.5 27
w/ raisins 7 1 Tbsp 29 21 0.6 28
Fortified Oat Flakes 3 1 Tbsp 29 21 0.6 11
40% Bran Flakes (Post ®) 6 2 Tbsp 30 20 0.7 19
Froot Loops ® 9 1/3 cup 29 20 0.6 37

Frosted Mini-Wheats ® 8 1 biscuit 38 22 0.8 28
Frosted Rice Krinkles ® 16 1/2 cup 34 44 0.8 62
Frosted Rice Krispies ® 14 1/2 cup 28 37 0.6 54
Fruit Wheat Squares 10 2 Tbsp 32 19 0.7 35
Fruity Pebbles™ 16 1/2 cup 28 37 0.6 66
Golden Grahams ® 10 1/4 cup 28 22 0.5 38
Grape Nuts Flakes ® 6 3 Tbsp 33 20 0.7 22
Honey Nut Cheerios ® 5 2 Tbsp 27 18 0.5 18
Honey Nut Corn Flakes ® 9 1/4 cup 31 25 0.6 38
Honeycomb ® 11 1/2 cup 33 26 0.6 43
King Vitaman ® 11 1/2 cup 29 23 0.5 43
Kix ® 6 1/3 cup 29 23 0.6 24
Life ® 3 1 Tbsp 28 20 0.5 10
Lucky Charms ® 6 3 Tbsp 30 20 0.5 23
Nutri-Grain ®
barley 5 2 Tbsp 31 19 0.6 19
corn 8 3 Tbsp 32 27 0.6 30
rye 8 3 Tbsp 31 21 0.7 27
wheat 5 2 Tbsp 25 15 0.5 20
Oat Flakes 3 1 Tbsp 29 21 0.6 11
Product 19 ® 6 3 Tbsp 31 23 0.6 24
Quisp ® 11 6 Tbsp 30 23 0.6 47
Raisin Bran (Post ®) 7 2 Tbsp 26 17 0.7 22
Rice Chex ® 13 1/2 cup 29 38 0.7 50
Rice Krispies ® 9 1/3 cup 27 36 0.6 37
Rice, puffed 10 3/4 cup 28 37 0.7 42
Special K ® 4 2 Tbsp 31 34 0.7 14
Sugar Frosted Flakes ® 12 1/3 cup 30 25 0.6 44
Sugar Pops ® 11 6 Tbsp 29 24 0.6 43
Sugar Smacks ® 9 1/4 cup 34 20 0.7 35
Sugar Sparkled Flakes 13 1/2 cup 35 29 0.7 64
Super Sugar Crisp ® 8 1/4 cup 28 16 0.5 31
Team ® 11 1/4 cup 32 31 0.7 41
Toasties (Post ®) 7 1/3 cup 29 24 0.6 27
Total ® 6 3 Tbsp 30 18 0.6 22
Trix ® 9 1/3 cup 27 21 0.5 35
Wheat
puffed 4 1/3 cup 30 17 0.6 14
shredded 5 1 Tbsp + 1-1/2 tsp 28 17 0.6 19
Wheat Chex ® 6 2 Tbsp 30 17 0.6 21
Wheaties ® 7 1/4 cup 33 20 0.7 25
Grains
Corn
cob (medium ear) 21 1/3 ear 30 25 0.6 19
cooked
cream style 32 2 Tbsp 26 21 0.6 23
whole kernel 20 2 Tbsp 32 26 0.7 22
Rice, prepared
brown, 25 2 Tbsp 32 24 0.6 27
cakes 9 1 cake 34 45 0.8 35
fried 23 1 Tbsp + 2 tsp 30 23 0.7 30
pilaf 15 1 Tbsp 30 20 0.6 23
Rice-A-Roni ® 21 1 Tbsp + 1 tsp 28 20 0.7 27
Spanish 30 2 Tbsp 26 21 0.5 26

white
long-grain 26 2 Tbsp 36 23 0.7 33
long-grain, instant 31 3 Tbsp 34 21 0.6 30
medium- and short-grain 26 2 Tbsp 32 20 0.6 33
Pasta, cooked
Macaroni 12 1 Tbsp + 1-1/2 tsp 31 18 0.6 18
Noodles 13 1 Tbsp + 1 tsp 26 14 0.5 17
Ramen ® Noodles 10 1 Tbsp 25 15 0.6 22
Spaghetti 19 2 Tbsp 33 17 0.6 21
Tubers
Potatoes, sweet
baked, w/ skin, mashed 25 2 Tbsp 26 18 0.4 26
boiled, no skin, mashed 31 1 Tbsp + 1-1/2 tsp 30 21 0.5 32
canned, packed in syrup 49 1/4 cup 26 18 0.4 67
Potatoes, white
baked, no skin 30 1/4 cup 31 26 0.7 33
boiled
no skin 39 1/4 cup 30 25 0.7 34
w/ skin 40 1/4 cup 32 28 0.8 34
canned 45 1/4 cup 28 24 0.3 27
French fries (1/2" x 1/2" x 2") 20 4 fries 32 19 0.7 64
hash browns, frozen/cooked 20 2 Tbsp 26 15 0.6 43
microwaved, w/ skin 29 3 Tbsp 27 23 0.6 29
pan fried 29 3 Tbsp 30 18 0.7 61
Tater Tots ® 37 4 pieces 33 19 0.8 61
Yams, baked or boiled 42 1/3 cup 29 17 0.6 49
Miscellaneous
Chocolate sauce (Hershey's ®) 20 1 Tbsp 25 18 0.5 49
Chow mein noodles 7 2 Tbsp 35 21 0.8 38
Flour, cake 8 1 Tbsp + 1 tsp 31 19 0.6 30
Jell-O ®, w/ sugar 80 1/3 cup 30 3 0.6 65
Snack Foods
Barnum's Animal Crackers ® 10 4 crackers 34 21 0.7 45
Cookies
fig bar 16 1 cookie 33 21 0.6 57
Ho Ho's ® 14 1/2 Ho Ho 27 17 0.6 60
Oreo ® 11 1 cookie 24 15 0.5 53
Social Tea Biscuit ® 11 2 biscuits 28 17 0.6 48
Sugar Wafer (Nabisco ®) 17 3 wafers 30 18 0.7 80
vanilla wafer 12 3 wafers 32 19 0.6 55
Crackers
Goldfish ®, original 9 15 crackers 29 19 0.6 44
graham cracker (2" x 2") 7 1 cracker 28 17 0.6 27
Ritz ® 10 3 crackers 32 19 0.7 50
Ritz Bits ® (cheese) 6 8 crackers 28 18 0.5 28
Rye Thins ® 8 3 crackers 27 12 0.6 39
Rykrisp ® 6 1 cracker 30 21 0.6 23
saltine 6 2 crackers 27 16 0.5 26
soda 7 1 cracker 35 19 0.7 30
Waverly ® 7 1 cracker 24 15 0.5 35
Wheat Thins ® 9 5 crackers 31 19 0.7 43
Doodads ® 7 2 Tbsp 34 22 0.8 35

Doritos ® 9 5 chips 28 17 0.7 44
Doughnuts, Ener-G ® Banana 84 2 doughnuts 31 10 0.8 309
Fritos ® 10 5 chips 30 22 0.7 55
Ice cream cone, wafer type 4 1 (cone only) 22 13 0.4 17
Popcorn
buttered 6 2/3 cup 31 26 0.6 27
caramel 9 1/4 cup 28 23 0.5 34
plain 4 2/3 cup 26 22 0.5 15
Potato chips (2" diameter) 10 5 chips 29 24 0.6 52
Rice cakes 9 1 cake 34 45 0.8 35
Tortillas
chips 8 1 chip 36 29 0.7 27
corn (6" diameter) 8 1/4 tortilla 36 29 0.7 27
flour (6" diameter) 8 1/4 tortilla 33 19 0.7 27
FATS
Butter, stick 14 1 Tbsp 6 6 0.1 101

Gravy
mushroom, canned 10 2 tsp 6 4 0.1 5
mushroom mix, dry 1 2 tsp 4 3 0.1 3
onion mix, dry 1 2 tsp 5 3 0.1 3
Margarine
liquid 5 1 tsp 4 4 0.1 34
soft 14 1 Tbsp 5 5 0.1 102
stick or brick 14 1 Tbsp 6 6 0.1 101
Nondairy creamers, w/ sodium caseinate
liquid 10 2 tsp 6 4 0.1 14
powder 2 1 tsp 5 5 0.1 11
Rich's ® Coffee Rich 29 2 Tbsp 4 3 0.1 44
Polyrich ® 29 2 Tbsp 4 3 0.1 44
Olives, black or green 10 2 olives 4 4 0.2 15
Salad dressings, commercial
French 16 1 Tbsp 4 4 0.1 67
Italian 15 1 Tbsp 4 4 0.1 69
mayonnaise 9 2 tsp 5 4 0.1 66
Thousand Island 16 1 Tbsp 6 6 0.1 59
Toppings, commercial
Cool Whip ®
extra creamy 5 1 Tbsp 6 6 0.1 15
regular 8 2 Tbsp 6 6 0.1 22
Richwhip ®
pressurized 22 3 Tbsp 5 4 0.1 60
prewhipped 8 2 Tbsp 5 4 0.1 24
Whipped cream, pressurized 4 1 Tbsp 6 6 0.1 10
FRUITS
Fruits are raw unless otherwise noted. Weight of raw fruits is only for parts that can be eaten. Drain canned, cooked, and frozen fruits before
measuring or weighing. Do not use any fruits that contain NutraSweet®, SweetMate®, or aspartame.
Apricots
canned, heavy syrup 64 1/4 cup 14 8 0.3 54
dried, halves 11 3 16 9 0.4 25
frozen, sweetened 60 1/4 cup 16 9 0.4 60
nectar, canned 94 3 fl oz 15 9 0.3 53
whole 35 1 fruit 18 10 0.5 17
Avocados, all varieties, mashed 23 1 Tbsp + 2 tsp 17 12 0.5 38
Bananas, sliced 42 3 Tbsp 16 10 0.4 39

Blackberries
canned, heavy syrup 25 2 Tbsp + 1-1/2 tsp 16 19 0.6 39
frozen 50 1/2 cup 17 20 0.6 32
raw 72 1/2 cup 15 17 0.5 38
Blueberries
raw 72 1/2 cup 17 6 0.5 41
Boysenberries, canned, heavy syrup 64 1/4 cup 18 13 0.6 56
Cherries
canned, heavy syrup
sour red 77 1/3 cup 12 5 0.6 70
sweet 86 1/3 cup 15 10 0.5 67
raw 48 1/3 cup 13 5 0.6 34
Dates 25 3 fruits 14 8 0.5 68
Figs
dried, uncooked 19 1 fruit 14 25 0.6 48
whole, large 83 1-2/3 fruit 15 27 0.6 61
Fruit cocktail, canned, heavy syrup 128 1/2 cup 14 9 0.4 93
Fruit salad, canned, heavy syrup 128 1/2 cup 14 10 0.4 94
Gooseberries, canned, light syrup 63 1/4 cup 15 5 0.4 46
Grapefruit, all varieties
canned, light syrup 85 1/3 cup 15 8 0.5 50
juice, canned, unsweetened 124 4 fl oz 19 13 0.6 48
sections 77 1/3 cup 16 8 0.5 24
Grapes
adherent skin 120 3/4 cup 16 14 0.8 86
juice, canned 126 4 fl oz 15 4 0.7 78
slipskin 92 1 cup 12 10 0.6 58
Thompson, seedless, canned, heavy syrup 128 1/2 cup 13 10 0.6 93
Kiwi fruit 50 2/3 piece 16 13 0.5 31
Mangoes, sliced 82 1/2 cup 14 9 0.4 54
Melons, cubed
cantaloupe 53 1/3 cup 13 8 0.5 18
casaba 57 1/3 cup 15 10 0.5 15
honeydew 85 1/2 cup 11 8 0.4 30
Mixed fruit, canned, heavy syrup 127 1/2 cup 14 10 0.5 92
Nectarines, sliced 52 6 Tbsp 16 12 0.5 25
Oranges
juice
canned 249 8 fl oz 17 7 1.5 105
frozen, diluted 187 6 fl oz 15 8 1.3 84
sections 45 1/4 cup 14 7 0.4 21
Papaya, cubed 140 1 cup 13 7 0.9 54
Passion fruit
juice 124 4 fl oz 14 10 0.5 63
whole, small 18 1 fruit 12 8 0.4 73
Peaches
dried 13 1/2 cup 15 12 0.5 31
nectar 187 6 fl oz 16 13 0.5 100
sliced 85 1/2 cup 18 16 0.6 37
spiced, canned, heavy syrup 121 1/2 cup 16 13 0.5 90
Pears
canned, heavy syrup 255 1 cup 13 5 0.5 188

halves, dried 35 2 17 6 0.7 92
sliced 165 1 cup 17 5 0.6 97
Persimmons, Japanese 56 1/3 fruit 15 9 0.4 39
Pineapple
canned, heavy syrup, chunks, tidbits, or crushed 191 3/4 cup 17 15 0.8 149
diced 116 3/4 cup 14 14 0.4 58
frozen, sweetened, chunks 122 1/2 cup 15 16 0.5 104
juice, canned, frozen, diluted 125 4 fl oz 15 13 0.5 65
Plantains, cooked 51 1/3 cup 14 10 0.4 60
Plums
cubed 82 1/2 cup 14 5 0.7 45
purple, canned, heavy syrup 194 3/4 cup 16 6 0.7 172
Prunes
juice 128 4 fl oz 17 6 0.8 90
whole, dried 25 3 fruits 15 6 0.7 60
Raisins, seedless 18 2 Tbsp 12 11 0.6 55
Raspberries
raw 62 1/2 cup 16 19 0.6 30
red, frozen, sweetened 83 1/3 cup 17 20 0.6 85
Rhubarb, cooked, sweetened 120 1/2 cup 14 9 0.5 139
Strawberries, sliced
raw 74 1/2 cup 13 16 0.5 23
Tangerines
canned, light syrup 84 1/3 cup 13 7 0.4 51
juice
canned, sweetened 249 8 fl oz 15 7 1.2 125
whole, medium 84 1 fruit 18 9 0.5 37
Watermelon, cubed 120 3/4 cup 18 14 0.7 38
VEGETABLES
Vegetables are raw unless otherwise noted. Weight of raw vegetables is only for parts that can be eaten. Drain canned and cooked
vegetables before measuring or weighing.
Asparagus
canned
green 30 2 Tbsp or 2 spears 15 9 0.6 6
white 38 2 spears 19 13 0.6 7
fresh or frozen, cooked 22 1-1/2 spears 16 10 0.6 6
raw 21 1-1/2 spears 16 10 0.7 7
Bamboo shoots, canned, sliced 25 3 Tbsp 15 12 0.4 5
Beans,
snap, green
canned 34 1/4 cup 14 9 0.4 7
fresh, cooked 16 2 Tbsp 14 9 0.4 7
frozen, cooked 34 1/4 cup 17 11 0.5 9
sprouts
mung (seed attached to sprout)
cooked 16 2 Tbsp 14 6 0.3 3
raw 13 2 Tbsp 15 7 0.4 4
soy
cooked 8 1 Tbsp 13 12 0.4 3
raw 6 1 Tbsp 12 11 0.4 3
yellow wax
canned 34 1/4 cup 14 9 0.4 7

Beets
red, sliced
fresh or canned, cooked 50 1/3 cup 15 12 0.5 15
pickled 50 1/3 cup 15 12 0.5 15
greens, cooked 18 2 Tbsp 12 11 0.5 5
Broccoli, fresh or frozen
cooked 20 2 Tbsp 18 13 0.6 6
raw 16 3 Tbsp 14 7 0.3 3
Brussels sprouts, fresh or frozen, cooked 21 1 sprout 16 12 0.5 8
Cabbage, shredded
Chinese (Pak-choi)
cooked 32 3 Tbsp 15 10 0.5 4
raw 35 1/2 cup 15 10 0.5 5
red
cooked 37 1/4 cup 13 7 0.4 8
raw 35 1/2 cup 15 8 0.5 10
white
cooked 52 1/3 cup 15 8 0.5 10
raw 35 1/2 cup 14 7 0.4 8
Carrots
canned 50 1/2 cup 15 9 0.5 17
fresh or cooked 39 1/4 cup 14 8 0.4 18
sliced 55 1/2 cup 18 11 0.6 24
Cauliflower
cooked 23 3 Tbsp 16 10 0.4 6
frozen, cooked 22 2 Tbsp 13 8 0.4 4
raw 25 1/4 cup 18 11 0.5 6
Celery, diced
cooked 75 1/2 cup 11 5 0.4 11
raw 60 1/2 cup 11 5 0.4 9
Chard, cooked 14 1 Tbsp + 1 tsp 15 11 0.2 3
Chayote, fruit, cooked 40 1/4 cup 14 10 0.2 10
Collards, cooked, chopped
fresh 48 1/4 cup 18 15 0.5 6
frozen 14 1 Tbsp + 1 tsp 14 11 0.4 5
Cucumber, pared, sliced 104 1 cup 16 9 0.6 14
Eggplant, cubed
cooked 48 1/2 cup 17 11 0.4 13
raw 31 6 Tbsp 14 9 0.3 8
Endive, raw, shredded 25 1/2 cup 13 10 0.3 4
Kale, cooked
fresh 16 2 Tbsp 16 11 0.3 5
frozen 11 1 Tbsp + 1 tsp 15 11 0.3 4
Kohlrabi, sliced
cooked 41 1/4 cup 17 12 0.7 12
raw 35 1/4 cup 14 17 0.6 10
Lettuce
bibb and Boston, raw 30 4 leaves 16 10 0.4 4
iceberg, shredded 28 1/2 cup 14 8 0.3 4
Romaine and cos, raw 20 2 leaves 14 8 0.3 4
Mushrooms,
Agaricus bisporus
cooked or canned 19 1/4 cup 15 8 0.4 5
raw, sliced 18 1 mushroom 15 8 0.4 5
Shitake
cooked 18 2 Tbsp 12 8 0.3 10

dried 4 1 mushroom 17 12 0.3 11
Mustard greens, cooked 26 3 Tbsp 16 31 0.6 4
Okra, pods or sliced, cooked 23 2 Tbsp 16 21 0.5 8
Onions
cooked 75 1/3 cup 15 15 0.7 20
raw, chopped 50 1/3 cup 15 15 0.6 15
rings, canned 25 1/2 cup 18 12 0.4 90
Parsnips, cooked 58 6 Tbsp 15 12 0.6 48
Peas, green, canned or frozen, cooked 10 1 Tbsp 17 10 0.5 7
Peppers, green, diced
cooked 68 1/2 cup 13 9 0.4 12
raw 50 1/2 cup 13 9 0.4 13
Pickles, cucumber
dill 104 1 large 16 9 0.6 14
dill relish 83 1/3 cup 12 7 0.4 14
sweet 83 1/3 cup 12 7 0.4 114
Pumpkin, canned 46 3 Tbsp 16 21 0.5 15
Radish
red, small 67 15 radishes 15 9 0.4 10
white icicle, sliced 50 1/2 cup 18 11 0.6 7
Rutabagas
cooked, mashed 60 1/4 cup 17 13 0.7 20
raw, cubed 44 1/3 cup 14 10 0.5 16
Sauerkraut 59 1/4 cup 17 9 0.5 11
Shallots, chopped 20 2 Tbsp 16 14 0.5 14
Spinach
fresh or frozen, cooked 12 1 Tbsp 16 13 0.4 2
raw, chopped 14 1/4 cup 18 15 0.4 3
Squash, summer, all varieties
fresh or frozen, cooked 45 1/4 cup 15 11 0.4 9
sliced 33 1/4 cup 14 10 0.4 7
Squash, winter
acorn
baked, cubed 38 3 Tbsp 17 15 0.4 21
boiled, mashed 61 1/4 cup 16 14 0.4 20
butternut
baked, cubed 51 1/4 cup 18 16 0.5 20
boiled, mashed 30 2 Tbsp 15 12 0.4 12
Hubbard
baked, cubed 26 2 Tbsp 15 13 0.6 13
boiled, mashed 30 2 Tbsp 17 15 0.4 9
spaghetti, cooked 51 1/3 cup 12 10 0.3 15
Taro, cooked 66 1/2 cup 18 13 0.3 94
leaves 18 2 Tbsp 20 18 0.5 4
root, sliced
Tomato
canned or fresh, cooked 60 1/4 cup 17 12 0.7 15
catsup 31 2 Tbsp 15 8 0.6 33
fresh
juice 92 3 fl oz 15 9 0.7 16
paste 16 1 Tbsp 13 8 0.6 14
purée 47 3 Tbsp 16 10 0.8 19
sauce
canned, w/ onions, green pepper, and celery 61 1/4 cup 17 11 0.8 19
marinara 47 3 Tbsp 16 10 0.8 32
whole, small 66 1/2 tomato 14 9 0.5 12

Turnips
greens
canned 25 2 Tbsp 17 10 0.4 4
root, diced
cooked 78 3/4 cup 16 12 0.9 21
raw 65 3/4 cup 16 12 0.9 27
Vegetable juice cocktail 91 3 fl oz 12 7 0.6 17
Soups, Campbell's ® Condensed. Weigh or measure before diluting and dilute with water only.
Asparagus, Cream of 21 1 Tbsp + 1 tsp 16 12 0.4 15
Celery, Cream of 31 2 Tbsp 20 14 0.4 22
Chicken Gumbo 21 1 Tbsp + 1 tsp 16 12 0.4 9
Chicken Vegetable 16 1 Tbsp 17 12 0.5 9
Mushroom, Cream of 20 1 Tbsp + 1 tsp 16 12 0.4 20
Onion 20 1 Tbsp + 1 tsp 16 15 0.7 9
Potato, Cream of 24 1 Tbsp + 1-1/2 tsp 15 12 0.3 14
Tomato 32 2 Tbsp 18 11 0.5 21
Tomato Bisque 26 1 Tbsp + 2 tsp 16 12 0.5 25
Tomato Rice 32 2 Tbsp 18 11 0.5 30
Vegetable, Old Fashioned 15 1 Tbsp 13 6 0.3 9
Vegetarian, Vegetable 15 1 Tbsp 13 6 0.3 9
FREE FOODS A
Limit to prescribed number of servings. Do not use beverages or foods that contain NutraSweet ®, SweetMate ®, or aspartame.
Desserts
Butterscotch chips 5 5 pieces 5 5 0.1 15
Gelatin pop 22 1/2 pop 5 1 0.3 16
Marmalade 19 1 Tbsp 3 2 0.1 50
Marshmallow 8 1 large 4 1 0.2 26
M&M ® candy, plain 2 2 pieces 6 4 0.2 8
Mocha Mix, frozen
chocolate 8 1 Tbsp 7 5 0.2 17
vanilla 8 1 Tbsp 5 4 0.1 17
Raisins, chocolate covered 2 2 raisins 6 6 0.2 12
Sorbet
peach 30 2 Tbsp 4 4 0.1 30
pineapple 59 1/4 cup 7 7 0.2 58
strawberry 59 1/4 cup 7 8 0.2 58
Fruits/Fruit Products
Apple
butter 40 2 Tbsp 4 3 0.2 74
canned, sweetened, sliced 102 1/2 cup 5 3 0.2 68
chips (Nature's Favorite ®) 15 1/4 cup 6 4 0.2 60
dried 21 1/4 cup 6 4 0.2 52
dried, cooked 64 1/4 cup 4 3 0.1 36
juice, frozen, diluted 120 2 fl oz 4 3 0.2 56
sauce, sweetened, canned 128 1/2 cup 6 4 0.2 97
whole, small 100 1 fruit 5 4 0.2 59
Cranberry sauce, canned 69 1/4 cup 5 1 0.1 104
Fruit bars, frozen
orange 37 1/2 bar 5 2 0.1 35
pineapple 37 1/2 bar 4 4 0.1 35
strawberry 74 1 bar 6 7 0.2 60
Fruit ice 48 1/4 cup 6 3 0.2 62

Fruit pie filling
apple 123 1/2 cup 4 3 0.1 135
cherry 47 3 Tbsp 5 2 0.2 49
peach 50 3 Tbsp 5 4 0.2 54
strawberry 31 2 Tbsp 5 5 0.2 34
Fruit Roll-Ups ® 14 1 piece 4 3 0.2 55
Lemonade 125 4 fl oz 4 2 0.1 55
Nectar
papaya 250 8 fl oz 5 3 0.4 142
peach 62 2 fl oz 5 4 0.2 34
pear 125 4 fl oz 4 1 0.1 75
Miscellaneous
Barbecue sauce 16 1 Tbsp 6 4 0.3 12
Chocolate
drink powder 3 1 tsp 4 3 0.1 11
pudding mix 7 2 tsp 6 4 0.1 23
syrup 6 1 tsp 5 4 0.1 14
Coconut, dried, sweetened w/ sugar 3 2 tsp 5 3 0.1 15
Coffee, instant, powder 2 1 tsp 5 3 0.2 4
Horseradish 2 2 tsp 4 4 0.1 2
FREE FOODS B
These foods contain little or no PHE or TYR. They may be used as desired if patient is not overweight and they do not depress appetite for
prescribed foods. Do not use beverages or foods that contain NutraSweet ®, SweetMate ®, or aspartame.
Beverages
Apple juice, canned 124 4 fl oz 2 2 0.1 60
Beer, regular 28 1 fl oz 2 4 0.1 12
Carbonated beverages, caffeine-free 113 4 fl oz 0 0 0.0 52
Cranberry juice cocktail 126 4 fl oz 1 1 0.0 72
Exceed ® Energy Drink 124 4 fl oz 0 0 0.0 35
Gatorade ® 125 4 fl oz 0 0 0.0 25
Kool-Aid ®, sweetened w/ sugar 125 4 fl oz 0 0 0.0 48
Liquor 28 1 fl oz 0 0 0.0 70
Limeade, sweetened w/ sugar 125 4 fl oz 0 0 0.0 51
Tang ® 125 4 fl oz 0 0 0.0 59
Tea, instant, powder 1 1 Tbsp 1 1 0.1 3
Wine 28 1 fl oz 1 1 0.1 21
Desserts/Sweeteners 1
Candies
Candy corn 16 10 pieces 0 0 0.0 58
Gumdrops 4 2 pieces 0 0 0.0 14
Hard candy 10 2 pieces 0 0 0.0 39
Jelly beans 28 10 pieces 0 0 0.0 103
Lollipop 28 1 medium 0 0 0.0 108
Frosting, strawberry and vanilla 16 1 Tbsp 0 0 0.0 69
Honey 21 1 Tbsp 3 2 0.1 64
Lemon pudding, canned (Hunt's ®) 121 1 can 0 0 0.0 151
Molasses 21 1 Tbsp 0 0 0.0 48
Popsicle ®, twin 128 1 popsicle 0 0 0.0 95
Sugar
brown 14 1 Tbsp 0 0 0.0 52
powdered 8 1 Tbsp 0 0 0.0 31
table 12 1 Tbsp 0 0 0.0 48

Syrup
corn 20 1 Tbsp 0 0 0.0 58
maple 20 1 Tbsp 0 0 0.0 50
table 20 1 Tbsp 0 0 0.0 50
Fruit butters 7 1 tsp 1 1 < 0.1 13
Fruit ices 1/2 cup 0 0 trace 69
Fruit juice bar 52 1 bar 2 1 0.1 43
Fun Fruits ® 26 1 piece 2 1 0.1 100
Guava
raw 90 1 fruit 2 9 0.7 45
sauce 119 1/2 cup 1 5 0.4 43
Jams 7 1 tsp 1 1 < 0.1 18
Jellies 20 1 Tbsp 0 0 0.0 50
Miscellaneous
Cornstarch 8 1 Tbsp 0 0 trace 29
Lard 13 1 Tbsp 0 0 0.0 115
Oil, vegetable 14 1 Tbsp 0 0 0.0 120
Richwhip ®, liquid 14 1 Tbsp 0 0 0.0 40
Shortening 13 1 Tbsp 0 0 0.0 113
Tapioca, dry 10 1 Tbsp 1 1 0.1 36
Vinegar/oil dressing 16 1 Tbsp 0 0 0.0 70
Wheat starch 8 1 Tbsp 1 1 trace 25
For nutrient composition of very-low-protein foods, see Appendix 12, p A-11.

TABLE 1-4. Nutrient Composition of PHENEX™-1 1, 3 and PHENEX-™2 2, 3
Nutrient Phenex-1 Phenex-2, Unflavored Phenex-2, Flavored

Per 100 g pwd Per g protein equiv Per 100 g pwd Per g protein equiv Per 100 g pwd Per g protein equiv
Energy, kcal 480 32 410 13.7 410 13.7
Protein equiv, g 15.00 1.000 30 1.000 30 1.000
Nitrogen, g 2.40 0.160 4.80 0.160 4.80 0.160
Amino acids, g 15.79 1.053 31.58 1.053 31.58 1.053
Cystine, g 0.15 0.010 0.30 0.010 0.30 0.010
Histidine, g 0.42 0.028 0.84 0.028 0.84 0.028
Isoleucine, g 1.08 0.072 2.16 0.072 2.16 0.072
Leucine, g 1.68 0.112 3.36 0.112 3.36 0.112
Lysine, g 1.00 0.067 2.00 0.067 2.00 0.067
Methionine, g 0.30 0.020 0.60 0.020 0.60 0.020
Phenylalanine, g trace 0 trace 0 trace 0
Threonine, g 0.70 0.047 1.40 0.047 1.40 0.047
Tryptophan, g 0.17 0.011 0.34 0.011 0.34 0.011
Tyrosine, g 1.50 0.100 3.00 0.100 3.00 0.100
Valine, g 1.22 0.081 2.44 0.081 2.44 0.081
Other Nitrogen-Containing Compounds
Carnitine, mg 20 1.33 40 1.33 40 1.33
Taurine, mg 40 2.67 50 1.67 50 1.67
Carbohydrate, g 53.0 3.53 35 1.17 36 1.20
Fat, g 21.7 1.45 14 0.47 13.5 0.45
Linoleic acid, g 2.00 4 0.133 1.50 5 0.050 1.50 5 0.050
6
α-Linolenic acid, g 0.36 0.024 0.17 7 0.006 0.17 7 0.006
Minerals
Calcium, mg 575 38 880 29 880 29
Chloride, mg/mEq 325/9.17 21.7/0.61 940/26.51 31.33/0.88 940/26.51 31.33/0.88
Chromium, µg 11 0.73 27 0.90 27 0.90
Copper, mg 1.10 0.073 1.00 0.033 1.00 0.033
Iodine, µg 65 4.33 100 3.33 100 3.33
Iron, mg 9.0 0.60 13 0.43 13 0.43
Phenylketonuria 27
Magnesium, mg 50 3.33 225 7.50 225 7.50

Manganese, mg 0.50 0.033 0.80 0.027 0.80 0.027
28 Phenylketonuria
Nutrient Phenex-1 Phenex-2, Unflavored Phenex-2, Flavored

Per 100 g pwd Per g protein equiv Per 100 g pwd Per g protein equiv Per 100 g pwd Per g protein equiv
Molybdenum, µg 12 0.80 30 1.00 30 1.00
Phosphorus, mg 400 27 760 25 760 25
Potassium, mg/mEq 675/17.26 45./1.15 1,370/35.04 45.7/1.17 1,370/35.04 45.7/1.17
Selenium, µg 20 1.33 35 1.17 35 1.17
Sodium, mg/mEq 190/8.26 12.7/0.55 880/38.28 29.3/1.28 880/38.28 29.3/1.28
Zinc, mg 8.0 0.53 13 0.43 13 0.43
Vitamins
A, µg RE 420 28 660 22 660 22
D, µg 7.50 0.50 7.50 0.25 7.50 0.25
E, mg α-TE 10.10 0.67 12.10 0.40 12.10 0.40
K, µg 50 3.33 60 2.00 60 2.00
Ascorbic acid, mg 50 3.33 60 2.00 60 2.00
Biotin, µg 65 4.33 100 3.33 100 3.33
B6, mg 0.75 0.050 1.30 0.043 1.30 0.043
B12, µg 4.90 0.327 5.00 0.167 5.0 0.167
Choline, mg 80 5.33 100 3.33 100 3.33
Folate, µg 230 15 450 15 450 15
Inositol, mg 40 2.67 70 2.33 70 2.33
Niacin equiv, mg 12.80 0.850 21.7 0.72 21.7 0.72
Pantothenic acid, mg 6.90 0.460 8.00 0.267 8.0 0.267
Riboflavin, mg 0.90 0.060 1.80 0.060 1.80 0.060
Thiamin, mg 1.90 0.127 3.25 0.108 3.25 0.108
1 2
3
Designed for infants and toddlers. Designed for children, adolescents, and adults.
Approximate packed weights in level, dry US standard household measures:
Phenex-1 Phenex-2, unflavored Phenex-2, flavored
1 Tbsp = 7g 8g 9g
1/4 cup = 26 g 32 g 30 g
1/3 cup = 35 g 41 g 40 g
1/2 cup = 53 g 61 g 59 g
1 cup = 105 g 117 g 116 g
4
Analytical data at manufacture = 4.32 g/100 g powder.
5
Analytical data at manufacture = 2.66 g/100 g powder in flavored.
6
Analytical data at manufacture = 0.40 g/100 g powder.
7
Analytical data at manufacture = 0.28 g/100 g powder in unflavored, 0.27 g/100 g powder in flavored.
TABLE 1-5. PKU Clinical Summary Sheet
Name: Hospital Number:
Date of Birth: __________/__________/__________

Mo Day Year
Date Age Physical Data Laboratory Data Nutrient Intake Data

Length/ Weight Head Hgb Ferritin Transthyretin PHE1 TYR1 PHE TYR Protein Energy
Height Circum
(mo/d/yr) (yrs/mo) (cm) (kg) (cm) (g/dL) (ng/mL) (mg/dL) (mg) (mg) (g) (kcal)
Phenylketonuria 29
1
Indicate if mg/dL or µmol/L.
REFERENCES
1. Acosta PB: The contribution of therapy of inherited amino acid disorders to knowledge of amino requirements. In
Wapnir RA (ed): Congenital Metabolic Diseases: Diagnosis and Treatment. New York: Marcel Dekker Inc, 1985,
(review), pp 115-135.
3. Acosta PB, Trahms C, Wellman NS, Williamson MW: Phenylalanine intakes of one to six year old children
undergoing therapy for PKU. Am J Clin Nutr 1983;38:694-700.
4. Acosta PB, Wenz E, Williamson M: Nutrient intakes of treated infants with phenylketonuria. Am J Clin Nutr
1977;30:198-208.
phenylketonuria. Acta Paediatr 1994;407 (Suppl):66-67.
6. Acosta PB,Yannicelli S: Plasma micronutrient concentrations in infants undergoing therapy for phenylketonuria.
Biol Tr Elem Res 1999;67:75-84.
7. Acosta PB, Yannicelli S, Marriage B, et al: Nutrient intake and growth of infants with phenylketonuria undergoing
therapy. J Pediatr Gastroent Nutr 1998;27:287-291.
8. Acosta PB, Yannicelli S, Marriage B, et al: Protein status of infants with phenylketonuria undergoing nutrition
management. J Am Col Nutr 1999;18:102-107.
9. Allen JR, McCauley JC, Waters DL, et al: Fasting energy expenditure in children with phenylketonuria. Am J Clin
Nutr 1995;62:797-801.
10. Anderson VE, Siegel FS: Behavioral and biochemical correlates of diet change in phenylketonuria. Pediatr Res
1976;10:10-17.
11. Arnold GL, Vladutiu CJ, Kirby RS: Protein insufficiency and impaired growth in children with PKU. J Inher Metab
Dis 2000;23 (Suppl 1):29A.
12. Azen CG, Koch R, Friedman EG, et al: Intellectual development in 12-year-old children treated for
phenylketonuria. Am J Dis Child 1991;145:35-39.
13. Behrman RE, Kleigman RM, Arvin AA (eds): Nelson Textbook of Pediatrics, ed 15. Philadelphia: WB Saunders Co,
1996.
population at risk for iron-deficiency anaemia and associated cognitive defects. Eur J Pediatr 1993;152:140-143.
15. Bohles H, Ullrich K, Endres W, et al: Inadequate iron availability as a possible cause of low serum carnitine
concentrations in patients with phenylketonuria. Eur J Pediatr 1991;150:425-428.
16. Calomme MR, Vanderpas JB, Francois B, et al: Thyroid function parameters during a selenium repletion/depletion
study in phenylketonuric subjects. Experientia 1995;51:1208-1215.
17. Carson DJ, Greeves LG, Sweeney LE, Crone MD: Osteopenia and phenylketonuria. Pediatr Radiol
1990;20:598-599.
18. Doherty LB, Rohr R, Levy HL: Detection of phenylketonuria in the very early newborn blood specimen. Pediatrics
1991;87:240-244.
19. Elsas LJ, Acosta PB: Nutrition support of inherited metabolic diseases. In Shils ME, et al (eds): Modern Nutrition in
Health and Disease, ed 9. Baltimore: Williams & Wilkins, 1999, pp 1003-1056.
20. Epstein CM, Trotter JF, Averbook A, et al: EEG mean frequencies are sensitive indices of phenylalanine effects on
normal brain. Electroencephalog Clin Neurophys 1989;72:133-139.
21. Fisch RO, Gravem HJ, Feinberg SB: Growth and bone characteristics of phenylketonurics: Comparative analysis
of treated and untreated phenylketonuric children. Am J Dis Child 1966;112:3-10.
23. Greeves LG, Carson DJ, Craig BG, McMaster D: Potentially life-threatening cardiac dysrhythmia in a child with
selenium deficiency and phenylketonuria. Acta Paediatr Scand 1990;79:1259-1262.
24. Greeves LG, Patterson CC, Carson DJ, et al: Effect of genotype on changes in intelligence quotient after dietary
relaxation in phenylketonuria and hyperphenylalaninaemia. Arch Dis Child 2000;82:216-221.
25. Griffiths PV, Demellweek C, Fay N, et al: Wechsler subscale IQ and subtest profile in early treated
phenylketonuria. Arch Dis Child 2000;82:209-215.
26. Gropper S, Acosta PB: Effect of simultaneous ingestion of L-amino acids and whole protein on plasma amino acid
and urea nitrogen concentrations in humans. JPEN 1991;15:48-53.
protein. J Pediatr Gastroent Nutr 1993;16:143-150.
28. Gropper SS, Trahms C, Cloud HA, et al: Iron deficiency without anemia in children with phenylketonuria. Int'l
Pediatr 1994;9:237-243.
29. Gropper SS, Yannicelli S: Plasma molybdenum concentrations in children with and without phenylketonuria. Biol
Trace Elem Res 1993;38:227-231.

30. Guldberg P, Mikkelsen I, Henriksen KF, et al: In vivo assessment of mutations in the phenylalanine hydroxylase
gene by phenylalanine loading: Characterization of seven common mutations. Eur J Pediatr 1995;154:551-556.
31. Guttler F, Guldberg P: Mutations in the phenylalanine hydroxylase gene: Phenotypic variability of
hyperphenylalaninemia. Acta Paediatr 1996;407 (Suppl):49-56.
32. Hanley WB, Feigenbaum ASJ, Clarke JTR, et al: Vitamin B12 deficiency in adolescents and young adults with
phenylketonuria. Eur J Pediatr 1996;S155:S145-S147.
33. Hanley WB, Linsao L, Davidson W, et al: Malnutrition with early treatment of phenylketonuria. Pediatr Res
1970;4:318-327.
34. Herbert V: Folic acid. In Shils ME, et al (eds): Modern Nutrition in Health and Disease, ed 9. Baltimore: Williams &
Wilkins, 1999, pp 433-446.
35. Herrmann ME, Broesicke HG, Keller M, et al: Dependence of the utilization of a phenylalanine-free amino acid
mixture on different amounts of single dose ingested. A case report. Eur J Pediatr 1994;153:501-503.
37. Ingall D, Sherman JD, Cockburn F: Immediate effects of phenylalanine-deficient diet in young infants. J Pediatr
1964;65:1073A.
38. Jones BJM, Lees R, Andrews J, et al: Comparison of an elemental and polymeric enteral diet in patients with
normal gastrointestinal function. Gut 1983;24:78-84.
39. Kindt E, Lunde HA, Gjessing LR, et al: Fasting plasma amino acid concentrations in PKU children on two different
levels of protein intake. Acta Paediatr Scand 1988;77:60-66.
40. Kindt E, Motzfeldt K, Halvorsen S, Lie S: Protein requirements in infants and children treated for phenylketonuria.
Am J Clin Nutr 1983;37:778-785.
41. Kindt E, Motzfeldt K, Halvorsen S, Lie SO: Is phenylalanine requirement in infants and children related to protein
intake? Br J Nutr 1984;51:435-442.
42. Kure S, Hou DC, Ohura T, et al: Tetrahydrobiopterin-responsive phenylalanine-hydroxylase deficiency. J Pediatr
1999;135:375-378.
43. Leverton RM, Johnson N, Ellison J, et al: The quantitative amino acid requirements of young women.
IV. Phenylalanine, with and without tyrosine. J Nutr 1956;58:341-353.
44. MacLean W, Graham G: Pediatric Nutrition in Clinical Practice. Menlo Park, Calif: Addison-Wesley Publishing Co,
1982.
45. Martin SB, Acosta PB: Osmotic behaviors of components of chemically-defined formulas. J Pediatr Perinat Nutr
1987;1:1-17.
46. Medical Research Council Working Party on Phenylketonuria: Recommendations on the dietary management of
47. Michals K, Lopus M, Matalon R: Phenylalanine metabolites as indicators of dietary compliance in children with
phenylketonuria. Biochem Med 1988;39:18-23.
48. Ohkohchi N, Andoh T, Ohi R, Mori S: Defined formula diets alter characteristics of the intestinal transport of amino
acids and peptides in growing rats. J Pediatr Gastroenterol Nutr 1990;10:490-496.
49. Posati LP, Orr ML: Composition of Foods: Dairy and Egg Products, Agriculture Handbook No. 8-1. Washington,
DC: US Dept of Agriculture, Agricultural Research Service, 1976.
1955;56:231-251.
51. Reilly C, Barrett JE, Patterson CM, et al: Trace element nutrition status and dietary intake of children with
phenylketonuria. Am J Clin Nutr 1990;52:159-165.
52. Rose WC, Wixom RL: The amino acid requirements of man. XIV. The sparing effect of tyrosine on the
phenylalanine requirement. J Biol Chem 1955;217:95-101.
53. Rouse BM: Phenylalanine deficiency syndrome. J Pediatr 1966;69:246-249.
54. Royston NJ, Parry TE: Megaloblastic anaemia complicating dietary treatment of phenylketonuria in infancy. Arch
Dis Child 1962;37:430-435.
56. Schuett VE, Brown ES, Michals K: Reinstitution of diet therapy in PKU patients from twenty-two US clinics. Am J
Publ Health 1985;75:39-42.
57. Schulpis KH, Nounopoulos C, Scarpalezou A, et al: Serum carnitine level in phenylketonuric children under dietary
control in Greece. Acta Paediatr Scand 1990;79:920-934.
58. Scriver CR, Kaufman S: Hyperphenylalaninemias. Phenylalanine hydroxylase deficiency. In Scriver CR, et al (eds):
The Metabolic and Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing
Division, 2001, pp 1667-1724.
59. Shortland D, Smith I, Francis DEM, et al: Amino acid and protein requirements in a preterm infant with classic
60. Sibinga MS, Friedman CJ, Steisel IM, Baker EC: The depressing effect of diet on physical growth in
phenylketonuria. Develop Med Child Neurol 1971;13:63-70.

61. Smith CA, Nelson NM (eds): The Physiology of the Newborn Infant, ed 4. Springfield, IL: Charles C Thomas
Publisher, 1976.
62. Smith JL, Arteaga C, Heymsfield SB: Increased ureagenesis and impaired nitrogen use during infusion of a
synthetic amino acid formula - A controlled trial. N Engl J Med 1982;306:1013-1018.
63. Smith I, Beasley MG, Ades AE: Effect on intelligence of relaxing the low phenylalanine diet in phenylketonuria.
Arch Dis Child 1990;65:311-316.
64. Smith I, Beasley MG, Ades AE: Intelligence and quality of dietary treatment in phenylketonuria. Arch Dis Child
1990;65:462-478.
65. Smith JL, Heymsfield SB: Enteral nutrition support: Formula preparation from modular ingredients. JPEN
1983;7:280-288.
66. Spaapen LJM, Bakker JA, Velter C, et al: Tetrahydrobiopterin-responsive hyperphenylalaninemia (HPA) in Dutch
neonates. J Inher Metab Dis 2000;23 (Suppl 1):45A.
67. Spika JS, Shaffer N, Hargrett-Bean N, et al: Risk factors for infant botulism in the United States. Am J Dis Child
1989;143:828-832.
68. Thompson AJ, Smith I, Brenton D, et al: Neurological deterioration in young adults with phenylketonuria.
Lancet 1990;336:602-605.
69. Trefz F, Burgard P, Konig T, et al: Genotype-phenotype correlations in phenylketonuria. Clin Chim Acta
1993;217:15-21.
70. Villasana D, Butler IJ, Williams JC, Roongta SM: Neurological deterioration in adult phenylketonuria. J Inher
Metab Dis 1989;12:451-457.
71. Waisbren SE, Levy HL: Agoraphobia in phenylketonuria. J Inher Metab Dis 1991;14:755-764.
72. Wannemacher RW: Key role of various individual amino acids in host response to infection. Am J Clin Nutr
1977;30:1269-1280.
73. Williams K: Benefits of normalizing plasma phenylalanine: Impact on behavior and health. A case report. J Inher
Metab Dis 1998;21:785-790.
74. Weir D, Scott JM: Vitamin B12 "cobalamin". In Shils ME, et al (eds): Modern Nutrition in Health and Disease, ed 9.
Baltimore: Williams & Wilkins, 1999, pp 447-458.
75. Yannicelli S, Davidson AJ, Van Doorninck WJ: Nutrition support for the late-treated adult with phenylketonuria.
Metabolic Currents 1990;2:9-14. Columbus, Ohio: Ross Laboratories.
76. Yannicelli S, Ernest A, Neifert MR, McCabe ERB: Guide to Breastfeeding the Infant With PKU, ed 2. Dept of Health
and Human Services Publication No. HRS-M-CH88-12, October 1988.

PROTOCOL 2 — Maternal Phenylketonuria (MPKU)
Nutrition Support of Pregnant Women With Phenylketonuria (PKU) With

PHENEX™-2 Amino Acid-Modified Medical Food
I. Introduction
Phenylketonuria (PKU) that is untreated at conception and during gestation is associated with poor
reproductive outcomes. Intrauterine growth retardation and congenital anomalies, often severe and
incompatible with life, are common. Most investigators attribute these effects to elevated maternal
plasma phenylalanine (PHE) concentrations. Lenke and Levy (25) described outcomes of
524 pregnancies in 155 women with PKU. The incidence of low birth weight, microcephaly, congenital
anomalies, and mental retardation in offspring was significantly higher than in the normal population.
The pathogenesis of fetal damage is uncertain, but is believed to be related to an elevated maternal
blood concentration of PHE (12, 20, 27) because PHE is actively transported across the placenta to
the fetus (24). Fetal blood PHE concentrations usually are significantly greater than those of maternal
blood (15) and interfere with embryonic development, although the mechanism of effect is not yet
known (12, 20, 27).
Offspring who survive fail to grow and develop normally. In fact, Kirkman (21) predicted that if these
women have normal fertility and dietary PHE intake is not controlled, the incidence of PKU-related
mental retardation could return to the prescreening level after only one generation.
II. Effects of Nutrition Support on Reproductive Outcome

A PHE-restricted diet and the gestational age at which it is initiated affect reproductive outcome. Of
576 pregnancies in the Maternal PKU Collaborative Study (MPKUCS), 414 resulted in live births
(22, 37). Only 125 women achieved and maintained blood PHE concentration < 600 µmol by
10 weeks gestation. Women who started the PHE-restricted diet before conception had a mean
plasma PHE concentration of 461 µmol/L (± SD of 233) during their 1st trimester of pregnancy. Those
who started the diet during the 1st trimester had a mean concentration of 661 µmol/L (± SD of 267).
Both mean concentrations were greater than the target range of 120 to 360 µmol/L.
Mean median head circumference percentile of offspring of the 25 women whose plasma PHE
concentration was less than 360 µmol/L by 10 weeks' gestation was significantly greater (58%) than
that of offspring of 35 women whose plasma PHE concentration was between 360 and 600 µmol/L by
10 weeks (41%). The mean General Cognitive Index (GCI) (McCarthy score) of offspring of women
who achieved control of plasma PHE concentration before 10 weeks' gestation was 94. Offspring of
women achieving control of plasma PHE concentration between 10 and 20 weeks' gestation had a
mean GCI of 87 and offspring of women not achieving control until after 20 weeks had a mean GCI of
72 (22, 23).
Rouse, et al (40) reported incidence of facial dysmorphology and major malformations in 35 infants in
the MPKUCS. Abnormally shaped ears, a wide palpebral fissure, epicanthical folds, and a long
philtrum were manifested in 50% to 70% of the offspring of mothers whose blood PHE concentration
was between 240 and 600 µmol/L. Fifteen percent of offspring of treated mothers had cardiac defects.
Intrauterine growth retardation ranged from 10% in offspring of women whose plasma PHE
concentration was between 240 and 600 µmol/L, to 100% in infants whose mother's PHE
concentration was more than 1200 µmol/L. Rouse, et al suggested that the mother's blood PHE
concentration should be lower than 360 µmol/L during pregnancy for the best outcome.
Smith et al (43) studied 94 infants of women with PKU, evaluating subjects by maternal blood PHE
concentration around the time of conception. Regression analysis of data from all 94 infants indicated
that birth weight decreased by 98 g and head circumference decreased by 0.46 cm for each
200 µmol/L increase in maternal blood PHE concentration above the normal range. Smith, et al
advised that a PHE-restricted diet should be started before conception and that blood PHE
concentration should be maintained between 60 and 180 µmol/L (43).
III. Establish Diagnosis

A. This protocol addresses nutrition support of women diagnosed with PHE hydroxylase deficiency.
See Protocol 1, p 2.
34 Maternal Phenylketonuria 2001 Ross Products Division

IV. Rationale for Nutrition Support
1. Restrict dietary PHE to amount tolerated by patient to maintain treatment plasma PHE
concentration.
1. Supplement dietary tyrosine (TYR) as necessary to maintain normal plasma TYR
concentration.
V. Establish Goals of Nutrition Support

1. Maintain 2- to 4-hour postprandial plasma PHE concentration between 2 and 4 mg/dL when
measured by bacterial inhibition assay and 120 and 240 µmol/L when measured by
quantitative methods) (10, 11, 29, 43, 46) or within normal range established by laboratory
used.
a. Frequent assessment of plasma PHE concentration is necessary for optimal nutrition
support and fetal outcome.
3. Differences of opinion exist as to best concentrations of plasma PHE and TYR for support of
normal fetal development and growth. Concentrations of plasma PHE and TYR as close to
normal as possible without restricting fetal growth are recommended (10, 30, 40, 43).
B. Plasma TYR Concentration
1. Maintain 2- to 4-hour postprandial plasma TYR concentration between 50 and 100 µmol/L
(0.9 and 1.8 mg/dL) or within normal range established by laboratory used.
C. Weight and Nutrition Status
1. Support normal and appropriate weight gain based on height, prepregnancy weight, and
gestational age (Table 2-1, p 41).
2. Recommended weight gain depends on weight at conception (47).
a. Normal-weight women should gain:
1) 1.60 kg (3.50 lb) in 1st trimester.
2) 0.44 kg (0.97 lb) per week during remainder of pregnancy.
3) 11 to 16 kg (25 to 35 lb) by 40 weeks' gestation.
b. Underweight women should gain:
1) 2.30 kg (5 lb) in 1st trimester.
3) 15 to 18 kg (34 to 40 lb) by 40 weeks' gestation.
c. Overweight women should gain:
1) 0.9 kg (2 lb) in 1st trimester.
3) 7 to 11.5 kg (15 to 25 lb) by 40 weeks' gestation.
3. Maintain normal nutrition status for pregnant woman (3, 8).
VI. Establish Prescription

A. PHE
1. Prescribe PHE intake that promotes goals of nutrition support.
2. PHE requirements vary widely:
a. From patient to patient, depending on activity of PHE hydroxylase which is dependent on
genotype (9).
1) Age.
2) Weight gain (39).
3) Trimester of pregnancy (39).
4) Adequacy of energy and protein intakes.
5) State of health.
© 2001 Ross Products Division Maternal Phenylketonuria 35
3. Lowest value for PHE in Table 2-2, p 41, is suggested to begin therapy.
a. Changing requirements are established only by frequent monitoring of plasma PHE
concentration of patient.
b. See Section IX, Suggested Evaluation of Nutrition Support, p 37.
4. PHE requirements usually increase at approximately 20 weeks' gestation (39, 46).
Warning: Inadequate PHE intake may lead to low maternal weight gain and poor
reproductive outcome.
B. TYR
1. Prescribe TYR intake that maintains treatment plasma TYR concentration.
2. Lowest value for TYR listed in Table 2-2, p 41, is suggested to start therapy.
3. Changing requirements of patients are determined only by frequent monitoring of plasma TYR
concentration.
C. Protein
1. See Table 2-2, p 41, for Recommended Protein Intakes.
2. Requirements are greater than Recommended Dietary Allowances (RDAs) when L-amino
acids supply majority of protein equivalent as result of:
a. Rapid amino acid absorption (14).
large part of protein is supplied by L-amino acids (14).
c. Rapid catabolism of amino acids (18, 19, 42, 44).
d. Possible decreased total amino acid absorption (34)
Warning: Inadequate protein intake is correlated with low birth length and poor weight
gain of offspring (1, 2, 30, 33).
3. Total protein intake of women in the MPKUCS was negatively correlated with plasma PHE
concentration throughout pregnancy and positively correlated with offspring birth measures
(2, 33).
4. Inadequate protein intake by women in the MPKUCS was associated with very low
intakes of folate and vitamin B12 and congenital heart defects in offspring (16, 17, 31,49).
D. Fat
1. Fat should supply 35% to 40% of energy.
a. 7% to 10% of energy should be obtained from linoleic acid (C18:2,n-6) (13).
b. 0.7% to 2.5% of energy should be obtained from α-linolenic acid (C18:3,n-3) (13).
2. Fat intake of women in the MPKUCS was negatively correlated with plasma PHE
concentration during pregnancy and positively correlated with offspring birth measures (2, 33).
E. Energy
1. Prescribe amount that should support appropriate weight gain (Table 2-2, p 41). Infant birth
measures are influenced by maternal energy intake and maternal weight gain (1, 2, 30, 33).
majority of protein equivalent (38).
3. Energy intake was negatively correlated with plasma PHE concentration during the last two
trimesters of pregnancy (2, 33).
Warning: Inadequate energy intake is associated with poor maternal weight gain,
decreased birth length and birth weight of offspring (1, 2, 31, 33), and
decreased maternal PHE tolerance.
F. Fluid
circumstances offer minimum of 1.0 mL for each kcal ingested.
VII. Fill Prescription
A. PHE
1. Calculate amount of table foods required to fill PHE prescription (Table 2-3, p 42).
a. Patients may select any food in prescribed Servings Lists for PHE-Restricted Diets
(Protocol 1, pp 16-26) in specified amounts to fill diet prescription.

2. If patient's appetite is small and PHE requirement is high:
a. Use bread, cheese, eggs, or whole cow's milk to help fill PHE prescription (Tables 2-3 and
2-4, p 42). These high-PHE foods usually are not required before 3rd trimester.
b. Measure whole cow's milk with large disposable syringe or standard volumetric flask.
B. Protein
1. Calculate amount of protein provided by table foods, bread, cheese, egg, or whole cow's milk
(Table 2-3, p 42) required to fill PHE prescription.
3. Supply any remaining prescribed protein with Phenex-2 (Table 2-5, p 43).
a. Weigh Phenex-2 powder on scale that reads in grams because of variability of household
measuring equipment (Practical Aspects of Nutrition Support, p vii) and changes in
b. See Table 2-5 (p 43, footnote 1) for approximate packed weight of Phenex-2 powder in
C. TYR
1. Calculate approximate amount of TYR provided by table foods, breads, whole cow's milk, or
whole egg (Table 2-3, p 42) required to fill PHE prescription.
2. Calculate amount of TYR supplied by Phenex-2 (Table 2-5, p 43) required to fill protein
prescription.
3. Subtract amounts determined above from total TYR prescription.
4. Provide any remaining prescribed TYR as L-TYR (Appendix 26, p A-28).
a. Supplement with L-TYR only if plasma TYR concentration is below 50 µmol/L
(0.9 mg/dL).
5. Make suspension of L-TYR of known TYR content per milliliter:
a. Weigh L-TYR powder and add sufficient boiled, cooled water to yield known volume.
b. Refrigerate in closed container until used. May be stored up to 1 week, if not frozen.
c. Shake well before using. Measure L-TYR into medical food mixture with disposable
syringe.
d. Solubility of L-TYR in water is low, about 50 mg/100 mL. Because of its low solubility,
some L-TYR may be mixed with fruit purées such as applesauce, sauces, soups, and
juices from Free Foods A and B in Servings Lists for PHE-Restricted Diets (Protocol 1,
pp 16-26).
6. L-TYR tablets (500 mg) are available at some pharmacies.
D. Fat
1. Use fats containing canola or soy oil as first ingredient to help supply α-linolenic acid.
E. Energy
1. Calculate energy provided by table foods, bread, cheese, egg, whole cow's milk (Table 2-3,
p 42), and Phenex-2 (Table 2-5, p 43) required to fill PHE and protein prescriptions.
2. Subtract amount of energy determined above from total energy prescription.
3. Provide any remaining prescribed energy with Free Foods B (Table 2-3, p 42), Polycose ®
Glucose Polymers Powder (23 kcal/Tbsp, 3.8 kcal/g), sugar (48 kcal/Tbsp), or other nitrogen-
free energy sources.
F. Fluid and Mixing Instructions
1. Add sufficient tap water or other fluid to ingredients to yield prescribed volume of medical food
mixture.
2. Mix with blender at lowest speed no longer than 4 seconds. Excess mixing may destabilize
emulsion. Medical food mixture may also be mixed in tightly closed container by shaking
vigorously for 10 to 12 seconds.
3. Place in container, cap, and store in refrigerator until used. Discard unused portion 24 hours
after mixing because of nutrient loss.
4. Do not heat because of Maillard reaction (Practical Aspects of Nutrition Support, p viii).
5. Chill Phenex-2 medical food mixture to improve taste.
6. Shake well before using.
G. Diet Guide
1. Provide patient with completed Diet Guide (Table 2-6, p 44) with each diet change.
2. Six small meals, including late-evening snack, may be better tolerated than three meals.
3. Late-evening snack containing at least 12 g of protein equivalent and 400 kcal may be helpful
in preventing usual early morning rise in blood PHE concentration (11).
VIII. Evaluate Adequacy and Safety of Planned Nutrition Support

A. Nutrient Adequacy (29)
1. Determine if diet provides nutrients in amounts prescribed in Section VI, Establish
Prescription, p 34.
2. Check Phenex-2 medical food mixture to determine if it supplies Recommended Dietary
Intakes (RDIs) for minerals and vitamins.
a. See Table 2-7, p 45, for RDIs.
b. See Appendix 8, p A-8, for complete nutrient composition of whole cow's milk and eggs.
c. Appendix 23, p A-25, may be used to check adequacy of nutrients if computer program is
not available.
d. If medical food used contains inadequate or no selenium, selenium deficiency and
decreased active thyroid concentration may occur (6).
3. If Phenex-2 mixture provides < 80% of RDIs, supplement diet with needed minerals and
vitamins if not supplied by table foods and laboratory tests indicate need.
a. Trace- and ultra-trace mineral deficiencies may occur if Phenex-2 fails to supply adequate
amounts (3).
b. Vitamin A from diet plus supplements should not exceed 400% of RDIs.
c. Folate and vitamin B12 supplementation are necessary prior to conception and
during trimester 1 if ingested medical food fails to supply requirements (31, 41).
d. Prenatal vitamin supplements are contraindicated if adequate medical food is ingested
due to the vitamin A they supply.
B. Osmolarity
1. If concentration of Phenex-2 is > 19 g mixed with water to yield 100 mL (3.3 fl oz), determine
if osmolarity is in acceptable range.
b. Osmolarity per gram of Phenex-2 is listed in Appendix 19, p A-21.
2. If osmolarity is > 1,000 mosm/L, or if patient does not tolerate initial feeds, dilute subsequent
feeds by equal volume of water (45).
a. Gradually increase concentration over 3 days, as tolerated.
IX. Suggested Evaluation of Nutrition Support

1. Evaluate twice weekly by quantitative methods.
2. Unacceptable PHE concentrations.
a. If plasma PHE concentration is not detected and patient has ingested full prescription:
1) Increase prescribed PHE by 25% and reevaluate plasma PHE concentration in 3 days.
2) If plasma PHE concentration continues undetected, repeat above process until value
b. If plasma PHE concentration is < 120 µmol/L (2 mg/dL) and patient has ingested full
prescription:
1) Increase prescribed PHE by 5% to 10% and reevaluate plasma PHE concentration in
3 days.
2) If plasma PHE concentration continues < 120 µmol/L (2 mg/dL), repeat above process
c. If plasma PHE concentration is > 240 µmol/L (4 mg/dL) and patient is not ill and has not
ingested more PHE or significantly less protein and energy than prescribed:
1) Decrease prescribed PHE by 5% to 10% and reevaluate plasma PHE concentration in
3 days.

2) If plasma PHE concentration continues > 240 µmol/L (4 mg/dL), repeat above process
B. Plasma amino acid concentrations (all) should be evaluated monthly by quantitative analysis.
1. Follow appropriate steps in Section IX, Suggested Evaluation of Nutrition Support, p 37,
Plasma PHE Concentration, if plasma PHE concentration is not in appropriate range.
C. Protein Status
1. Evaluate plasma transthyretin concentration monthly (Appendix 17, p A-18, for standards).
concentration in 1 month. If plasma PHE concentration is in treatment range, use
Phenex-2 to increase protein.
b. Repeat above process until transthyretin concentration is in treatment range.
D. Iron Status
1. Plasma ferritin concentration.
a. Evaluate monthly (Appendix 17, p A-18, for standards).
1) Add 60 mg elemental iron as ferrous sulfate daily and reevaluate in 1 month.
2) Continue iron supplements until plasma ferritin concentration is in treatment range.
2. Complete blood count
a. Hemoglobin and hematocrit should be evaluated each trimester (Appendix 17, p A-18, for
standards).
E. Erythrocyte Folate and Serum Vitamin B12 Concentrations
1. Evaluate preconception, at first visit after conception, and each trimester (8, 16, 17, 39, 49).
2. If erythrocyte folate concentration is < 200 ng/mL (17):
a. Supplement with 400 to 800 µg of folacin daily and reevaluate in 1 month.
b. If folacin concentration is not in normal range, continue supplement and reevaluate in
1 month.
3. If serum vitamin B12 is < 300 pg/mL (49):
a. Supplement with 2.2 to 4.0 µg vitamin B12 per day and reevaluate in 1 month.
b. If vitamin B12 concentration is not in normal range, continue supplement and reevaluate
again after 1 month.
F. Weight Gain
1. Evaluate weekly during 1st month of treatment and monthly thereafter.
2. If weight gain is below recommended (Section V, Establish Goals of Nutrition Support, p 34)
and all prescribed diet has been regularly ingested:
a. Increase prescribed energy by 5% to 10% and reevaluate weight gain in 1 week.
b. If weight gain is still inadequate, repeat above process until appropriate weight gain occurs.
G. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of PHE, TYR, protein, energy, minerals, and vitamins for 3 days immediately
before each blood test.
a. Vitamin A intakes > 4500 µg RE (15,000 IU) daily MUST be avoided (48) because
excess vitamin A is a teratogen.
3. After each diet change, evaluate mineral and vitamin intakes:
a. See Table 2-7, p 45, for normal standards for pregnant women.
c. See Appendix 8, p A-8, for nutrient composition of whole cow's milk and eggs.
4. For further information on nutrition support of pregnant women, see reference 32.

H. Clinical Summary
1. A summary record of weight gain, laboratory, and nutrient intake data is useful for patient
X. Sample Prescriptions
A. Example 1
Establish and fill prescription for pregnant 24-year-old woman who is 167.6 cm tall and weighs
56 kg (normal weight) at beginning of pregnancy and 63.3 kg at 27 weeks' gestation using
Recommended Daily Nutrient Intakes from Table 2-2, p 41, and average nutrient contents from
Tables 2-3 and 2-5, pp 42 and 43.
1. Establish prescription for 1st trimester.
PHE 200 mg/day
TYR 7,000 mg (7.0 g)
Protein 70 g
Energy 2,500 kcal
Fluid 2,500 mL
2. Fill prescription for 1st trimester.
Phenex-2 217 g 0 6,510 65.1 890
L-TYR 352 mg 0 352 0.0 0
Add water to make 1183 mL (40 fl oz). Additional fluid should be consumed ad libitum daily.
Food List Servings

Fats 5 25 20 0.5 300
Fruits 3 45 30 1.5 180
Free Foods A 2 10 8 0.2 130
Free Foods B 16 0 0 0.0 880
Total per day 200 7,000 70.1 2,500
3. Establish prescription for 3rd trimester.
PHE 875 mg/day
TYR 7,000 mg (7.0 g)
Protein 70 g
Energy 2,500 kcal
Fluid 2,500 mL

4. Fill prescription for 3rd trimester.
Phenex-2 169 g 0 5,070 50.7 693
Whole cow's milk 195 mL 320 320 6.6 123
Sugar 2 tsp 0 0 0 32
1
L-TYR 1,234 mg 0 1,234 0 0
Add water to make 1183 mL (40 fl oz). Additional fluid should be consumed ad libitum daily.
Food List Servings

Breads/Cereals 13 390 260 7.8 390
Fats 9 45 36 0.9 540
Fruits 4 60 40 2.0 240
Free Foods B 8 0 0 0.0 440
Total per day 875 7,000 70.0 2,498
1
Mix with soups, purées, and juices from Free Foods B in Servings Lists for PHE-Restricted Diets
(Protocol 1, pp 13-26), or use L-TYR tablets.
XI. Management of Problems During Pregnancy (7)

A. Nausea
1. Suggest patient try one or more of following:
a. Eat small amounts of prescribed food hourly while awake.
b. Eat some prescribed low-protein crackers before rising in morning.
c. Drink fluids (except medical food mixture) between meals.
d. Avoid fried foods.
e. Eat lightly seasoned foods.
f. Eat plain fruits and vegetables.
g. Eat some prescribed food before preparing meal.
h. Avoid strong, unpleasant odors.
B. Heartburn
a. Eat slowly.
b. Chew food well.
c. Eat small, frequent meals.
d. Avoid spicy and/or fried foods.
e. Sit straight up or walk after eating.
f. Avoid bending or stooping after eating.
C. Constipation
a. Drink more water.
b. Eat some fruits with skins and raw vegetables.
c. Increase fiber by selecting cereal with fiber.
d. Drink some prune juice daily (may be mixed with soft drinks, not diet, to improve flavor).
e. Exercise daily.

TABLE 2-1. Prepregnancy Weights for Heights
Height Underweight If Normal Weight Range1 Midpoint of Overweight If

Without Shoes This Weight or Normal Weight This Weight or
Less Range More
(ft/in) (cm) (lb) (kg) (lb) (kg) (lb) (kg) (lb) (kg)
4'10" 147.32 88 40.0 89 - 108 40.4 - 49.0 98.5 44.7 109 49.5
4'11" 149.86 91 41.4 92 - 112 41.8 - 50.9 102.0 46.4 113 51.4
5' 152.40 94 42.7 95 - 115 43.2 - 52.3 105.0 47.7 116 52.7
5'1" 154.94 99 45.0 100 - 121 45.5 - 55.0 110.5 50.2 122 55.5
5'2" 157.48 104 47.3 105 - 127 47.7 - 57.7 116.0 52.7 128 58.2
5'3" 160.02 108 49.0 109 - 132 49.5 - 60.0 120.5 54.8 133 60.5
5'4" 162.56 113 51.4 114 - 138 51.8 - 62.7 126.0 57.3 139 63.2
5'5" 165.10 118 53.6 119 - 144 54.1 - 64.5 131.5 59.8 145 65.9
5'6" 167.64 123 55.9 124 - 150 56.4 - 68.2 137.0 62.3 151 68.6
5'7" 170.18 127 57.7 128 - 155 58.2 - 70.5 141.5 64.3 156 70.9
5'8" 172.72 132 60.0 133 - 161 60.5 - 73.2 147.0 66.8 162 73.6
5'9" 175.26 137 62.3 138 - 167 62.7 - 75.9 152.5 69.3 168 76.4
5'10" 177.8 142 64.5 143 - 173 65.0 - 78.6 158.0 71.8 174 79.1
5'11" 180.34 146 66.4 147 - 178 66.8 - 80.9 162.5 73.0 179 81.4
6' 182.88 151 68.6 152 - 184 69.1 - 83.6 168.0 76.4 185 84.1
1
Normal weight for "thin-boned" women will be closer to lower end of range. For "big-boned" women, weight will be
closer to higher end.
TABLE 2-2. Recommended Daily Nutrient Intakes (Ranges) for Pregnant Women With PKU
Trimester and Age Nutrient

(yrs) PHE1,2 TYR 1, 2 Protein3 Energy 3, 4 Fluid5
(mg/day) (g/day) (g/day) (kcal/day) (mL/day)
1st Trimester
15 to < 19 200 - 600 5.75 - 7.50 ≥ 75 2,500 (2000 - 3500) 2,000 - 3,500
≥ 19 200 - 600 4.50 - 7.00 ≥ 70 2,500 (2000 - 3000) 2,000 - 3,000
2nd Trimester
15 to < 19 200 - 900 5.75 - 7.50 ≥ 75 2,500 (2000 - 3500) 2,000 - 3,500
≥ 19 200 - 900 4.50 - 7.00 ≥ 70 2,500 (2000 - 3000) 2,000 - 3,000
3rd Trimester
15 to < 19 300 - 1200 5.75 - 7.50 ≥ 75 2,500 (2000 - 3500) 2,000 - 3,500
≥ 19 300 - 1200 4.50 - 7.00 ≥ 70 2,500 (2000 - 3000) 2,000 - 3,000
1
Initiate prescription with lowest value for age and trimester. Actual requirement may vary considerably. Modify
prescription based on frequently obtained plasma values and maternal weight gain.
2
From references 1, 2, 26, 30, 32, 33.
3
4
For 15- to < 19-year-old, energy intake should never be < 45 kcal/kg of ideal pregnancy weight. For women
≥ 19 years of age, energy intake should never be < 35 kcal/kg of ideal pregnancy weight (35). Adequate energy to
support recommended weight gain (Section V, Establish Goals of Nutrition Support, p 34) should be prescribed even
if number is greater than highest number listed for trimester and age.
5
Under normal circumstances, offer minimum of 1 mL fluid for each kcal ingested (5).

TABLE 2-3. Serving Lists for PHE-Restricted Diets: Average Nutrient Content per Serving1
Food List Nutrient

Fats 5 4 0.1 60
Fruits 15 10 0.5 60
Breads 116 67 2.2 79
Cheeses 365 337 6.8 95
Egg, whole, 1 large (~50 g), 2 332 255 6.2 74
Whole cow's milk, 100 mL 2 164 164 3.39 63
1
From reference 10.
2
TABLE 2-4. Serving Lists for PHE-Restricted Diets: Supplemental Foods

For greatest accuracy, weigh food on scale that reads in grams.
BREADS
Biscuit, commercially baked 35 1 biscuit 108 67 2.2 127
Bun, hamburger and hot dog, plain 43 1 bun 179 106 3.6 123
Cracked wheat 25 1 slice 105 63 2.2 65
French, Vienna or sourdough 25 1 slice 109 62 2.2 68
Italian 20 1 slice 87 50 1.8 54
Pumpernickel 26 1 slice 110 62 2.3 65
Raisin 26 1 slice 94 53 2.0 71
Rye, American 32 1 slice 132 68 2.7 83
White 25 1 slice 101 59 2.0 67
Whole wheat 28 1 slice 130 81 2.7 69
Mean 116 67 2.2 79
CHEESE
American, processed 28 1 slice 319 344 6.3 106
Blue (3/4" x 1" x 1") 28 1 piece 308 367 6.1 100
Camembert 28 1 slice 313 325 5.6 85
Cheddar 28 1 slice 372 341 7.1 114
Colby 28 1 slice 355 325 6.7 112
Cottage, creamed 56 1/4 cup 378 374 7.0 58
Gouda 28 1 slice 406 412 7.0 101
Monterey Jack 28 1 slice 365 335 6.9 106
Mozzarella, low-moisture, part skim 28 1 slice 407 450 7.8 79
Muenster 28 1 slice 352 318 6.6 104
Parmesan, grated 16 3 Tbsp 336 348 6.2 68
Provolone 28 1 slice 365 431 7.2 100
Swiss 28 1 slice 471 480 8.1 106
Mean 365 337 6.8 95

TABLE 2-5. Nutrient Composition of PHENEX™-2 1
Nutrient Phenex-2, Unflavored Phenex-2, Flavored

Per 100 g pwd Per g protein equiv Per 100 g pwd Per g protein equiv
Energy, kcal 410 13.7 410 13.7
Protein equiv, g 30.00 1.000 30.00 1.000
Nitrogen, g 4.80 0.160 4.80 0.160
Amino acids, g 31.58 1.053 31.58 1.053
Cystine, g 0.30 0.010 0.30 0.010
Histidine, g 0.84 0.028 0.84 0.028
Isoleucine, g 2.16 0.072 2.16 0.072
Leucine, g 3.36 0.112 3.36 0.112
Lysine, g 2.00 0.067 2.00 0.067
Methionine, g 0.60 0.020 0.60 0.020
Phenylalanine, g trace 0 trace 0
Threonine, g 1.40 0.047 1.40 0.047
Tryptophan, g 0.34 0.011 0.34 0.011
Tyrosine, g 3.00 0.100 3.00 0.100
Valine, g 2.44 0.081 2.44 0.081
Carnitine, mg 40 1.33 40 1.33
Taurine, mg 50 1.67 50 1.67
Carbohydrate, g 35 1.17 36 1.20
Fat, g 14 0.47 13.5 0.45
2 2
Linoleic acid, g 1.50 0.050 1.50 0.050
α-Linolenic acid, g
3 3
0.17 0.006 0.17 0.006
Minerals
Calcium, mg 880 29 880 29
Chloride, mg/mEq 940/26.51 31.33/0.88 940/26.51 31.33/0.88
Chromium, µg 27 0.90 27 0.90
Copper, mg 1.00 0.033 1.00 0.033
Iodine, µg 100 3.33 100 3.33
Iron, mg 13 0.43 13 0.43
Magnesium, mg 225 7.50 225 7.50
Manganese, mg 0.80 0.027 0.80 0.027
Molybdenum, µg 30 1.00 30 1.00
Phosphorus, mg 760 25 760 25
Potassium, mg/mEq 1,370/35.04 45.7/1.17 1,370/35.04 45.7/1.17
Selenium, µg 35 1.17 35 1.17
Sodium, mg/mEq 880/38.28 29.3/1.28 880/38.28 29.3/1.28
Zinc, mg 13 0.43 13 0.43
Vitamins
A, µg RE 660 22 660 22
D, µg 7.50 0.25 7.50 0.25
E, mg α-TE 12.10 0.40 12.10 0.40
K, µg 60 2.00 60 2.00
Ascorbic acid, mg 60 2.00 60 2.00
Biotin, µg 100 3.33 100 3.33
B6, mg 1.30 0.043 1.30 0.043
B12, µg 5.0 0.167 5.0 0.167
Choline, mg 100 3.33 100 3.33
Folate, µg 450 15 450 15
Inositol, mg 70 2.33 70 2.33
Niacin equiv, mg 21.7 0.72 21.7 0.72
Pantothenic acid, mg 8.00 0.267 8.00 0.267
Riboflavin, mg 1.80 0.06 1.80 0.06
Thiamin, mg 3.25 0.108 3.25 0.108
1
Approximate packed weight in level, dry US standard household measures:
Phenex-2, unflavored Phenex-2, flavored
1 Tbsp = 8g 9g
1/4 cup = 32 g 30 g
1/3 cup = 41 g 40 g
1/2 cup = 61 g 59 g
1 cup = 117 g 116 g
2
Analytical data at manufacture = 2.75 g/100 g powder in unflavored and 2.66 g/100 g powder in flavored.
3
Analytical data at manufacture = 0.28 g/100 g powder in unflavored and 0.27 g/100 g powder in flavored.

TABLE 2-6. PHE-Restricted Diet Guide
Name: _____________________________________________________
Date: ______ _/__ _____/_ ______ Weight: ______________________(kg)
Mo Day Year
Medical Food Amount

Phenex-2, unflavored, flavored Tbsp/cup/g
Tbsp/cup/g
Tbsp/cup/g
Add water to make ____________________ mL (__________________ fl oz).
Daily Intake Servings PHE TYR Protein Energy

BREAKFAST
Medical Food Mixture, fl oz
Breads/Cereals
Fats
Fruits
Cheese/Eggs/Regular Bread
Free Foods A
Free Foods B
MIDMORNING SNACK
LUNCH
Breads/Cereals
Fats
Fruits
Vegetables
Free Foods A
Free Foods B
MIDAFTERNOON SNACK
DINNER
Breads/Cereals
Fats
Fruits
Vegetables
Free Foods A
Free Foods B
BEDTIME SNACK
DAILY TOTAL
Comments:
_____________________________________________
Nutritionist
TABLE 2-7. Recommended Dietary Intakes (RDIs) for Pregnant Women1
Nutrient Age (yr)

15 to <19 > 19
Minerals
Calcium, mg 1,300 1,000
Chloride, mEq 40 - 117 48 - 144
Copper, mg 2.5 2.5
Iodine, µg 175 175
Iron 2, mg 48 48
Magnesium, mg 450 450
Manganese, mg 3.75 3.75
Phosphorus, mg 1,250 1,250
Potassium, mEq 39 - 117 48 - 144
Selenium, µg 65 65
Sodium, mEq 39 - 117 48 - 144
Zinc, mg 20 20
Vitamins
A, µg RE 1,000 1,000
D, µg 5 5
E, mg α-TE 15 15
K, µg 65 65
Ascorbic acid, mg 80 85
Biotin, µg 30 30
B6, mg 2.6 2.6
B12, µg 4 4
Folate, µg 800 800
Niacin equiv3, mg 18 18
Pantothenic acid, mg 6.0 6.0
Riboflavin, mg 1.6 1.6
Thiamin, mg 1.5 1.5
1
Modified from references 13, 50.
2
From reference 3.
3
From reference 28.

46 Maternal Phenylketonuria
TABLE 2-8. MPKU Clinical Summary Sheet
Date of Birth: __________/__________/__________ Age: _______(yrs) Usual Prepregnancy Weight: __________ kg Height:________ (cm)
Mo Day Year
Date of Last Menstrual Period: _________/__________/_________ Diet Started: _________/__________/_________

Mo Day Year Mo Day Year
Wks Preconception: _________________ Wks Gestation: _________________ When Diet Initiated: _________________
Date Physical Data Laboratory Data Nutrient Intake Data

Gestation Weight Weight Hgb Hct Transthyretin Ferritin Folate1 PHE2 TYR2 PHE TYR Protein Energy
Age Gain
(mo/d/yr) (wk) (kg) (kg) (g/dL) (%) (mg/dL) (µg/L) (mg) (mg) (g) (kcal)
1
2
Indicate if RBC or serum and method.
REFERENCES
1. Acosta PB: Nutrition support of maternal PKU. Sem Perinat 1995;19;182-190.
2. Acosta PB, Michals-Matalon K, Austin V, et al: Nutrition findings and requirements in pregnant women with
phenylketonuria. In Platt L (ed): Effects of Genetic Disorders on Pregnancy Outcome. London: Parthenon Publ,
1997, pp 21-32.
3. Acosta PB, Stepnick-Gropper S, Clarke-Sheehan N, et al: Trace element status of PKU children ingesting an
elemental diet. JPEN 1987;11:287.
Dis 2000;23 (Suppl 1):29A.
5. Behrman RE, Kliegman RM, Arvin AA (eds): Nelson Textbook of Pediatrics, ed 15. Philadelphia: WB Saunders Co,
1996.
study. Experientia 1995;51:1208-1215.
7. Castiglioni LL, Rouse BM: The Young Woman With PKU. Galveston, Texas: University of Texas, 1986.
8. Committee on Nutrition of the Mother and Preschool Child, Food and Nutrition Board, National Research Council:
Laboratory Indices of Nutritional Status in Pregnancy. Washington, DC: National Academy of Sciences, 1978.
9. Danks DM, Cotton RGH: Future developments in phenylketonuria. In Tada T, et al (eds): Recent Advances in
Inborn Errors of Metabolism. New York: S Karger, 1987.
11. Farquhar DL, Steven F, Westwood A: Preliminary report on inverse diurnal variation of phenylalanine: Implications
in maternal phenylketonuria. Hum Nutr Appl Nutr 1985;39A:224-226.
12. Fisch RO, Burke B, Bass J, et al: Maternal phenylketonuria — Chronology of the detrimental effects on
embryogenesis and fetal development: Pathological report, survey, clinical application Pediatr Pathol
1986;5:449-461.
15. Hanley WB, Clarke JTR, Schoonheyt W: Maternal phenylketonuria (MPKU): A review. Clin Biol 1986:20:149-56.
16. Hanley WB, Feigenbaum ASJ, Clarke JTR, et al: Vitamin B12 deficiency in adolescents and young adults with
phenylketonuria. Eur J Pediatr 1996;S155:S145-S147.
17. Herbert V: Folic acid. In Shils ME, et al (eds): Modern Nutrition in Health and Disease, ed 9. Baltimore: Williams &
Wilkins, 1999, pp 433-446.
mixture on different amounts of a single dose ingested. A case report. Eur J Pediatr 1994;153:501-503.
20. Kirby ML, Miyagawa ST: The effects of high phenylalanine concentration on chick embryonic development. J Inher
Metab Dis 1990;13:634-640.
21. Kirkman HN: Projections of a rebound in frequency of mental retardation from phenylketonuria. Appl Res Mental
Retard 1982;3:319-328.
22. Koch R, Friedman E, Azen C, et al: The international collaborative study of maternal phenylketonuria status report
1998. Mental Retard Devpt Disabilities Research Rev 1999;5:117-121.
23. Koch R, Friedman EG, Wenz E, et al: Maternal phenylketonuria. J Inher Metab Dis 1986;9 (Suppl 2):159-168.
24. Kudo Y, Boyd CAR: Transport of amino acids by the human placenta: Predicted effects thereon of maternal
hyperphenylalaninemia. J Inher Metab Dis 1990;13:617-626.
25. Lenke RR, Levy HL: Maternal phenylketonuria and hyperphenylalaninemia. An international survey of the outcome
of untreated and treated pregnancies. N Engl J Med 1980;303:1202-1208.
26. Leverton RM, Johnson N, Ellison J, et al: The quantitative amino acid requirements of young women.
IV. Phenylalanine, with and without tyrosine. J Nutr 1956;58:341-353.
27. Levy HL: Maternal phenylketonuria: Review with emphasis on pathogenesis. Enzyme 1987;38:312-320.
28. Lewis JS, Loskill S, Bunker ML, et al: N-Methylnicotinamide excretion of phenylketonuric children and a child with
Hartnup disease before and after phenylalanine and tryptophan load. Fed Proc 1974;33:666A.
29. Lynch BC, Pitt DB, Maddison TG, et al: Maternal phenylketonuria: Successful outcome in four pregnancies treated
prior to conception. Eur J Pediatr 1988;148:72-75.
30. Matalon R, Michals K, Azen C, et al: Maternal PKU collaborative study: The effect of nutrient intake on pregnancy
outcome. J Inher Metab Dis 1991;14:371-374.
31. Matalon KM, Acosta PB, Azen C, Matalon R: Congenital heart disease in maternal phenylketonuria: Effects of
blood phenylalanine and nutrient intake. Mental Retard Devpt Disabilities Research Rev 1999;5:122-124.
48 Maternal Phenylketonuria © 2001 Ross Products Division

32. Matalon K, Acosta PB, Castiglioni L, et al: Protocol for Nutrition Support of Maternal Phenylketonuria. Bethesda.
The National Institute of Child health and Human Development, 1999.
33. Michals K, Acosta PB, Austin V, et al: Nutrition and reproductive outcome in maternal phenylketonuria. Eur J
Pediatr 1996;155 (Suppl 1): S165-S168.
35. Oldham H, Sheft BB: Effect of caloric intake on nitrogen utilization during pregnancy. J Amer Diet Assoc
1951;27:847-854.
37. Platt LD, Koch R, Hanley WB, et al: The international study of pregnancy outcome in women with maternal
phenylketonuria. Report of a 12-year study. Am J Obstet Gynecol 2000;182:1-8.
1955;56:231-251.
39. Rohr FJ, Doherty LB, Waisbren SE, et al: New England maternal PKU project: Prospective study of untreated and
treated pregnancies and their outcomes. J Pediatr 1987;110:391-398.
40. Rouse B, Azen C, Koch R, et al: Maternal phenylketonuria collaborative study (MPKUCS) offspring: Facial
anomalies, malformations, and early neurological sequelae. Am J Med Genet 1997;69:89-95.
41. Rouse B, Matalon R, Koch R, et al: Maternal phenylketonuria syndrome: Congenital heart defects, microcephaly,
and developmental outcomes. J Pediatr 2000;136:57-61.
43. Smith I, Glossop J, Beasley M: Fetal damage due to maternal phenylketonuria: Effects of dietary treatment and
maternal phenylalanine concentrations around the time of conception. J Inher Metab Dis 1990;13:651-657.
1983;7:280-288.
46. Soeters RP, Sengers RC, van Dongen PW, et al: Maternal phenylketonuria: Comparison of two treated full-term
pregnancies. Eur J Pediatr 1986;145:221-223.
47. Subcommittee on Nutritional Status and Weight Gain During Pregnancy: Nutrition and Pregnancy. Washington,
DC: National Academy Press, 1990.
48. Rothman KJ, Moore LL, Singer MR, et al: Teratogenicity of high vitamin A intake. N Engl J Med
1995;333:1369-1373.
49. Weir D, Scott JM: Vitamin B12 "cobalamin". In Shils ME, et al (eds): Modern Nutrition in Health and Disease, ed 9.
Baltimore: Williams & Wilkins, 1999, pp 447-458.
50. Yates AA, Schlicker SA, Suitor CW: Dietary reference intakes: The new basis for recommendations for calcium
and related nutrients, B vitamins, and choline. J Amer Diet Assoc 1998;98;699-706.

PROTOCOL 3 — Tyrosinemia Types Ia and Ib
Nutrition Support of Infants, Children and Adults With

TYREX ®-1 and TYREX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
Five clinical forms of hereditary tyrosinemia have been reported. Type Ia is caused by a primary defect
of hepatic fumarylacetoacetate hydrolyase (FAH) (13) with production of an abnormal metabolite,
succinylacetone, which is formed from the accumulated substrate fumarylacetoacetate (Figure B). If
maleylacetoacetic acid isomerase is functional, succinylacetone is also formed from
maleylacetoacetate. Succinylacetone is extremely toxic and is associated with impaired active
transport functions and disordered hepatic enzymes, including p-hydroxyphenylpyruvic acid
dioxygenase (p-OHPPAD) and δ-aminolevulinic acid (δ-ALA) dehydratase (30). Decreased activity of
both hepatic and erythrocyte δ-ALA dehydratase has been reported in these patients and is postulated
as the mechanism by which acute porphyric-like episodes develop (30). Inhibition of p-OHPPAD using
the drug 2 (2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclo-hexanedione (NTBC) has prevented acute
porphyric episodes and decreased rates of progression of cirrhosis and Fanconi syndrome (20, 21).
Dietary protein
Tissue protein synthesis

Phenylalanine*
Tissue protein
catabolism CO2 + H2O
Melanin
Tyrosine* Epinephrine
Thyroxine
p-Hydroxyphenylpyruvic acid*
p-OH phenylpyruvic acid dioxygenase¹
Homogentisic acid
Maleylacetoacetic acid isomerase (type Ib)
Maleylacetoacetic acid*
Succinylacetoacetic
Fumarylacetoacetic acid*
acid*
Fumarylacetoacetic acid hydrolyase (type Ia)
Succinylacetone*
* Accumulates In untreated
Fumaric acid tyrosinemia type Ia
+ ¹ Inhibited by NTBC
Acetoacetic acid Enzyme malfunction
Figure B. Tyrosine metabolism in tyrosinemia types Ia and Ib

Tyrosinemia type Ia is characterized by generalized renal tubular impairment with hypophosphatemic
rickets, progressive liver failure producing cirrhosis and hepatic cancer, hypertension, episodic
behavioral and peripheral nerve deficiencies, and elevated concentrations of blood phenylalanine
(PHE) and tyrosine (TYR) with succinylacetone and δ-ALA excretion in urine (30). FAH is expressed in
amniotic and chorionic villus cells and prenatal diagnosis is available by biochemical or molecular
techniques (30). Soon after birth, infants with the acute form of tyrosinemia type Ia develop
progressive liver and kidney failure, vomiting, diarrhea, and a "cabbage-like" odor.
50 Tyrosinemia Types Ia and Ib 2001 Ross Products Division

Because some of these symptoms are similar to other inborn errors of metabolism, accurate diagnosis
is essential. Increased concentrations of PHE and TYR are found in the blood (13, 30).
The chronic form of tyrosinemia type Ia is similar to the acute form, but symptoms are usually milder
and appear later in infancy. Symptoms include rickets, liver and kidney dysfunction, high blood
pressure, and nervous system dysfunction. Liver hepatomas often develop on or before 10 years of
age, even in well-treated patients (13, 30). Incidence of tyrosinemia type Ia varies. Overall incidence
in Quebec, Canada, is 1/12,500 live births (30). Therapy with a PHE and TYR-restricted diet and
administration of NTBC to prevent succinylacetone accumulation is now the standard of care for
tyrosinemia type Ia.
Tyrosinemia type Ib, believed to be due to deficiency of maleylacetoacetate isomerase (Figure B), has
been reported in 1 infant (8, 30). Liver failure, renal tubular disease, and progressive psychomotor
retardation occurred prior to death at 1 year of age. Succinylacetone did not accumulate.
II. Outcome of Nutrition Support

Liver transplantation has significantly improved outcome in patients with tyrosinemia type Ia. Without
liver transplantation, patients develop hepatomas (12), usually within the 1st or 2nd decade of life.
NTBC has dramatically improved the course of patients with tyrosinemia type I (20, 21, 23, 26, 33).
Whether hepatomas will develop in patients treated with NTBC is unknown (23). If hepatomas do not
develop, liver transplantation may be unnecessary. Medical and nutrition support are essential to
maintain optimal health and nutrition status until a suitable liver is found. Long-term data on patients
with a liver transplant are not yet available.

A. The Defect
1. Tyrosinemia may result from defect in 1 of several enzymes.
a. Type Ia: Fumarylacetoacetate hydrolyase (17, 30).
b. Type Ib: Maleylacetoacetate isomerase (8).
c. Type II: Tyrosine aminotransferase (Protocol 4, p 63).
d. Type III: Parahydroxyphenylpyruvic acid dioxygenase (14, 30) (Protocol 4, p 63).
1) No liver enzyme activity (30).
2) Hawkinsinuria (30).
3) Transient, neonatal.
B. Clinical Screening
1. Concentration of > 4 mg TYR/dL (13) by bacterial inhibition assay of dried blood spot requires
differential diagnosis.
2. Because few states screen for tyrosinemia, infants or children with any of following clinical
findings associated with hepatosplenomegaly and nephropathy should be evaluated for
tyrosinemia types Ia and Ib (7, 12, 30):
a. Failure to thrive.
b. Vomiting and/or diarrhea.
c. Jaundice.
d. Fanconi syndrome.
e. Rickets.
f. Some patients may not develop renal tubular dysfunction or rickets (43).
C. Differential Diagnosis
3. This protocol addresses nutrition support for patients with deficiency of FAH or
maleylacetoacetate isomerase.

1. Restrict dietary PHE and TYR to amounts tolerated by patient to maintain treatment plasma
amino acid concentrations.
© 2001 Ross Products Division Tyrosinemia Types Ia and Ib 51

B. Reduce Transcription of Gene
1. Reduce transcription of δ-ALA dehydratase gene with high-carbohydrate diet if δ-ALA is
present in urine (9).
2. The high-carbohydrate diet may be unnecessary with use of NTBC.

A. Plasma PHE and TYR Concentrations
1. Maintain 2- to 4-hour postprandial plasma PHE and TYR concentrations in ranges noted below
when measured by quantitative methods, or within normal range for age established by
laboratory used.
Amino Acid µmol/L mg/dL
PHE 35 - 90 0.58 - 1.49
TYR 40 - 80 0.72 - 1.45
3. Differences of opinion exist as to best concentrations of plasma PHE and TYR to support
normal growth and development in infants and children with tyrosinemia types Ia and 1b and
to prevent development of hepatomas.
a. In this protocol, concentrations as close to normal as possible are assumed to be best.
b. With use of NTBC, plasma TYR concentrations will be greater than without its use but
should be maintained as close to normal range as possible.
c. With plasma PHE and TYR concentrations in normal range, plasma amino acids
must be measured frequently to prevent deficiency (11).
B. Growth, Development, and Nutrition Status
1. Support normal growth rate in infants and children.
2. Support normal development.
3. Maintain normal nutrition status (10).
5. Maintain plasma bicarbonate, phosphate, and potassium in normal range for age.
6. Maintain plasma and urine free of, or containing only traces of, succinylacetone and
parahydroxyphenyl organic acids.
7. Maintain urine free of, or containing only traces of, δ-ALA.
8. Prevent rickets (19).
C. Neurologic Status
1. Prevent neurologic crises (31, 36).
D. Hepatic and Renal Status
1. Maintain normal liver and renal function (23-25, 37, 38, 43, 45).
2. Support patient nutritionally until appropriate liver can be found to transplant (37), if indicated.

A. PHE Plus TYR (5)
1. Prescribe PHE plus TYR intake that promotes goals of nutrition support.
2. PHE plus TYR requirement varies widely:
a. From patient to patient, depending on activity of fumarylacetoacetate hydrolyase.
b. In same patient, depending on age, growth rate, adequacy of protein and energy intakes,
and state of health.
3. Lowest value for age for PHE plus TYR listed in Table 3-1, p 58, is suggested for initiating
therapy.
4. Changing requirements of patients are determined by frequent monitoring of:
a. Plasma PHE and TYR concentrations.
b. Plasma and urine concentrations of succinylacetone and parahydroxyphenyl organic
acids.
c. See Section IX, Suggested Evaluation of Nutrition Support, p 54.
Warning: Inadequate PHE plus TYR intake results in anorexia, lethargy, hypotonia,
decreased growth rate in infants and children, decreased plasma fibrogen,
and increased plasma amino acid concentrations (except PHE and TYR) (11).
B. Protein
1. Prescribe, initially, amount greater than Recommended Dietary Allowances (RDA) (15)
(Table 3-1, p 58).
3. If blood ammonia concentration is elevated, protein intake may need to be restricted until
ammonia level returns to normal range.
Warning: Inadequate protein intake will result in failure to thrive, weight loss, low
plasma transthyretin concentrations, osteopenia, hair loss, and decreased
PHE and TYR tolerance.
C. Energy
1. Prescribe amount that should support normal weight gain for infants and toddlers (Table 3-1,
p 58).
majority of protein equivalent (18, 35).
3. To help prevent neurologic crises if NTBC is not used, 50-65% of energy should be derived
from carbohydrate (9).
4. See Appendix 26, p A-28, for source of NTBC.
Warning: Inadequate energy intake may precipitate metabolic and neurologic crises as
result of muscle protein catabolism.
D. Fluid
circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid to children and
adults for each kcal ingested.
2. Supply greater than normal amounts because of greater than normal energy intake.
E. 1,25 Dihydroxycholecalciferol (Rocaltrol ®)
1. Use in presence of elevated alkaline phosphatase and/or decreased plasma phosphate, or
radiographic evidence of rickets.
2. Prescribe 0.25-1.0 µg of Rocaltrol daily, if needed.

A. PHE Plus TYR
1. Calculate amount of infant formula with iron, beikost, whole cow's milk, or table foods
(Table 3-2, p 58) required to fill PHE plus TYR prescription.
a. Low-iron infant formula, whole cow's milk, or evaporated milk should not be used as PHE
plus TYR source for infants because of low iron content.
2. Measure liquid infant formula, and whole cow's milk with disposable syringe. Weigh powdered
infant formula on scale that reads in grams.
3. Add beikost or table foods to gradually displace PHE plus TYR provided by infant formula
after infant is 3 to 4 months old or is developmentally ready.
4. Parents or patients may select any food in prescribed Servings Lists for PHE-Restricted Diets
B. Protein
3. Supply remaining prescribed protein with Tyrex (Table 3-3, p 59).
a. Tyrex-1 is for infants and toddlers and Tyrex-2 is for children and adults.
b. Weigh Tyrex powder on scale that reads in grams because of variability of household
c. See Table 3-3 (p 59, footnote 3) for approximate packed weight of Tyrex powder in level,
dry US standard household measures.
C. Energy
1. Calculate energy provided by infant formula with iron, beikost, whole cow's milk, or table foods
(Table 3-2, p 58), and Tyrex (Table 3-3, p 59) required to fill PHE plus TYR and protein
prescriptions.
Free Foods B (Table 3-2, 58), depending on age of patient.
4. At least 50% of energy prescription should be derived from carbohydrate (9) if patient
tolerates osmolarity of medical food mixture.
D. Fluid and Mixing Instructions
1. Add sufficient boiled, cooled water to infant formula, Tyrex, and carbohydrate to yield
prescribed volume. Tap water may replace boiled, cooled water when preparing Tyrex for
older infants and children.
2. Mix with sterilized blender at lowest speed no longer than 3 to 4 seconds. Excess mixing
may destabilize emulsion. Medical food may also be mixed in tightly closed container by
shaking vigorously for 10 to 12 seconds.
mixing because of nutrient loss.
5. Warm or cool medical food mixture to room temperature before feeding to infants. Shake
mixture well before feeding.
6. Do not warm medical food mixture for infants in microwave oven. Unevenly heated formula
can burn infants, and steam can make bottles explode.
8. For children and adults, chill Tyrex medical food mixture to improve taste.
E. Diet Guide
1. Provide parents or caretakers with completed Diet Guide (Appendix 22, p A-24) with each diet
change.
2. Feed infant 6 to 8 times daily (18, 39).
3. Feed children and adults 4 to 6 times daily (18, 39).

Prescription, p 51.
a. See Table 3-3, p 59, for composition of Tyrex.
b. See Table 3-2, p 58, for average composition of infant formulas and whole cow's milk.
vitamins (Appendices 13 and 14, pp A-14 and A-15).
a. See Appendices 4 through 7, pp A-4 to A-7, for average nutrient composition of infant
formulas.

b. Appendix 23, p A-25, may be used to check adequacy of nutrients if computer program is
not available.
c. If Tyrex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
supplement diet with needed minerals and vitamins if not provided by beikost or table
foods and laboratory tests indicate need (Appendix 11, p A-10, for composition of
supplements).
B. Osmolarity
b. Osmolarity per gram of Tyrex is listed in Appendix 19, p A-21.
2. If osmolarity is > 450 mosm/L for neonates, > 750 mosm/L for children, or is greater than that
tolerated by patient, increase water content of prescribed medical food mixture and
recalculate its osmolarity (27).
renal solute load.
recalculate.
IX. Suggested Evaluation of Nutrition Support (13)

1. Initial.
approximate dietary PHE and TYR requirements are known.
2. Ongoing.
b. Evaluate plasma PHE and TYR concentrations weekly until infant is 1 year old and once
or twice monthly thereafter.
3. Unacceptable plasma PHE or TYR concentrations.
a. If plasma PHE or TYR concentration is not detected and patient has ingested full
prescription:
1) Increase prescribed amount of undetected amino acid(s) by 25% and reevaluate
plasma concentrations in 3 to 4 days.
2) If plasma PHE or TYR concentration continues undetected, repeat above process
b. If plasma PHE concentration is < 35 µmol/L (0.58 mg/dL) or plasma TYR concentration is
< 40 µmol/L (0.72 mg/dL) and patient has ingested full prescription:
1) Increase prescribed amount of amino acid(s) that is low by 5% to 10% and reevaluate
plasma concentration in 3 to 4 days.
2) If plasma PHE or TYR concentration continues to be low, repeat above process until
value is in treatment range.
c. If plasma PHE is > 90 µmol/L (1.49 mg/dL) or plasma TYR is > 80 µmol/L (1.45 mg/dL)
and the patient is not ill and has not ingested more or less protein and energy than
prescribed:
1) Decrease prescribed amount of elevated amino acid(s) by 5% to 10% and reevaluate
plasma concentration in 3 to 4 days.
2) If plasma PHE or TYR concentration continues to be high, repeat above process until

B. Organic Acids in Urine
1. Evaluate succinylacetone and parahydroxyphenyl organic acids monthly or if plasma TYR is
elevated.
C. Protein Status
1. Evaluate plasma transthyretin concentration every 3 months in infants and twice yearly in
children and adults (Appendix 17, p A-18, for standards).
a. Increase prescribed protein by 5% to 10% if blood ammonia is normal and reevaluate in
1 month. If plasma PHE and TYR concentrations are in treatment range, use Tyrex to
increase protein.
D. Iron Status
1) Increase iron intake to 4 mg/kg body weight with supplements (ferrous sulfate).
E. Plasma and Urine Biochemistries
1. Plasma and urine phosphate, potassium, and bicarbonate concentrations.
a. Evaluate monthly.
b. Maintain in normal range for age as established by laboratory used.
2. Plasma chloride, sodium, liver enzymes, and alkaline phosphatase concentrations.
a. Maintain in normal range for age and laboratory standards (29).
b. Evaluate every 3 months.
c. If alkaline phosphatase concentration is elevated, obtain radiographs of bones for
evaluation of rickets (2).
F. Growth Status
a. Measure monthly to 1 year and every 6 months thereafter until adulthood. Plot
measurements on NCHS growth charts.
infants and children will fall above or below these percentiles.
a. Increase prescribed protein (from Tyrex) and energy by 5% to 10% and remeasure in
1 month.
achieved.
G. Nutrient Intake
and 25, pp A-26 and A-27).

not available.
I. Special Concern
1. Because of the high risk of hepatomas, periodic serum α-fetoprotein concentrations and liver
imaging studies (by computer-assisted tomography, ultrasonography, or magnetic resonance
imaging) should be obtained.
H. Clinical Summary
A. Example 1
Establish and fill prescription for newborn weighing 3.3 kg using Recommended Daily Nutrient
Intakes from Table 3-1, p 58, and nutrient contents from Tables 3-2 and 3-3, pp 58 and 59.
PHE and TYR 65 mg/kg x 3.3 kg = 214 mg
Tyrex-1 61 g 0 0 9.2 293
Similac With Iron RTF 186 mL 110 108 2.6 126
Total per day 110 108 11.8 419
Total per kg 33 33 3.6 127
Total PHE plus TYR 218
load is < 130 mosm.
B. Example 2
Nutrient Intakes from Table 3-1, p 58, and average nutrient contents from Tables 3-2 and 3-3,
pp 58 and 59.
PHE and TYR 380 mg
Protein 30 g
Energy 1,300 kcal
Fluid 1,365 mL

Tyrex-2 80 g 0 0 24.0 328
Sugar 102 g (8.5 Tbsp) 0 0 0.0 408
Food List Servings

Fruits 4 60 40 2.0 240
Free Foods A 3 15 12 0.3 195
Total per day 225 152 30.1 1,301
Approximate osmolarity is < 750 mosm/L.
XI. Nutrition Support During Febrile Illness or Following Trauma

A. Rationale
protein (46).
2. Well-nourished patients with tyrosinemia respond to infection and trauma as do normal
persons.
3. Extent of protein catabolism determines subsequent elevations in plasma PHE and TYR
concentrations.
Jell-O ®, Polycose powder or liquid (Appendix 9, p A-9), or Pro-Phree (Appendix 11,
p A-10) added to fruit juices or Pedialyte if tolerated and caffeine-free soft drinks (not diet
drinks).
1) 1/3 cup of Polycose powder may be added to liquid Pedialyte to yield 8 fl oz.
b. Return patient to Tyrex medical food mixture and pre-illness diet as rapidly as possible.
1) Begin with 1/2 original strength of Tyrex medical food mixture.

TABLE 3-1. Recommended Daily Nutrient Intakes (Ranges) for Infants and Children With
Tyrosinemia Types Ia and Ib
Age Nutrient
1 2
PHE plus TYR Protein Energy2 Fluid3
(mg/kg) (g/kg) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 65 - 155 3.50 - 3.00 120 (145 - 95) 160 - 135
3 to < 6 mo 55 - 135 3.50 - 3.00 120 (145 - 95) 160 - 130
6 to < 9 mo 50 - 120 3.00 - 2.50 110 (135 - 80) 145 - 125
9 to < 12 mo 40 - 105 3.00 - 2.50 105 (135 - 80) 135 - 120
(mg/day) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 380 - 800 ≥ 30 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 390 - 900 ≥ 35 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 400 - 1,000 ≥ 40 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 800 - 1,200 > 50 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 800 - 1,200 > 55 2,100 (1200 - 3000) 1,200 - 3,000
> 19 yr 800 - 1,000 > 60 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 990 - 1,200 > 55 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 1,000 - 1,500 > 65 2,800 (2100 - 3900) 2,100 - 3,900
> 19 yr 1,000 - 1,500 > 70 2,900 (2000 - 3300) 2,000 - 3,300
1
Modified from references 1, 4, 13, 42. Initiate therapy with lowest value for age range. Modify prescription based on
frequently obtained plasma values and growth.
2
3
Modified from reference 6. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid
to children and adults for each kcal ingested.
TABLE 3-2. Serving Lists for PHE- and TYR-Restricted Diets: Average Nutrient Content per Serving1
Food List Nutrient

Fats 5 4 0.1 60
Fruits 15 10 0.5 60
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 2 86 29 1.86 68
2
Isomil ® Soy Formula With Iron, Ready to Feed, 100 mL 88 60 1.66 68
2
1
From reference 13.
2
3

TABLE 3-3. Nutrient Composition of TYREX ®-11, 3 and TYREX ®-22, 3
Nutrient Tyrex-1 Tyrex-2

(per 100 g pwd) (per g protein equiv) (per 100 g pwd) (per g protein equiv)
Energy, kcal 480 32.0 410 13.7
Protein equiv, g 15.00 1.000 30.00 1.000
Nitrogen, g 2.40 0.160 4.80 0.160
Amino acids, g 14.73 0.982 29.46 0.982
Cystine, g 0.15 0.010 0.30 0.010
Histidine, g 0.42 0.028 0.84 0.028
Isoleucine, g 1.08 0.072 2.16 0.072
Leucine, g 1.68 0.112 3.36 0.112
Lysine, g 1.00 0.067 2.00 0.067
Methionine, g 0.30 0.020 0.60 0.020
Phenylalanine, g trace 0 trace 0
Threonine, g 0.70 0.047 1.40 0.047
Tryptophan, g 0.17 0.011 0.34 0.011
Tyrosine, g trace 0 trace 0
Valine, g 1.22 0.081 2.44 0.081
Carnitine, mg 20 1.33 40 1.33
Taurine, mg 40 2.67 50 1.67
Carbohydrate, g 53.0 3.53 35 1.17
Fat, g 21.7 1.45 14.0 0.47
4 5
Linoleic acid, g 2.00 0.133 1.50 0.050
6 7
0.36 0.024 0.17 0.006
Minerals
Calcium, mg 575 38 880 29
Chloride, mg/mEq 325/9.17 21.7/0.61 940/26.51 31.33/0.88
Chromium, µg 11 0.73 27 0.90
Copper, mg 1.10 0.073 1.00 0.033
Iodine, µg 65 4.33 100 3.33
Iron, mg 9.0 0.60 13 0.43
Magnesium, mg 50 3.33 225 7.50
Manganese, mg 0.50 0.033 0.80 0.027
Potassium, mg/mEq 675/17.26 45/1.15 1,370/35.04 45.7/1.17
Selenium, µg 20 1.33 35 1.17
Sodium, mg/mEq 190/8.26 12.7/0.55 880/38.28 29.3/1.28
Zinc, mg 8.0 0.53 13 0.43
Vitamins
A, µg RE 420 28 660 22
D, µg 7.50 0.50 7.50 0.25
E, mg α-TE 10.10 0.67 12.10 0.40
K, µg 50 3.33 60 2.00
Biotin, µg 65 4.33 100 3.33
B6, mg 0.75 0.050 1.30 0.043
B12, µg 4.90 0.327 5.00 0.167
Choline, mg 80 5.33 100 3.33
Folate, µg 230 15 450 15
Inositol, mg 40 2.67 70 2.33
Niacin equiv, mg 12.80 0.850 21.7 0.72
Riboflavin, mg 0.90 0.060 1.80 0.060
Thiamin, mg 1.90 0.127 3.25 0.108
1 2
Designed for infants and toddlers. Designed for children and adults.
3
Approximate packed weights of Tyrex-1 and Tyrex-2 in level, dry US standard household measures:
Tyrex-1 Tyrex-2
1 Tbsp = 7g 8g
1/4 cup = 26 g 32 g
1/3 cup = 35 g 41 g
1/2 cup = 53 g 61 g
1 cup = 105 g 117 g
4 5
Analytical data at manufacture = 4.32 g/100 g powder. Analytical data at manufacture = 2.66 g/100 g powder.
6 7

60 Tyrosinemia Types Ia and Ib
TABLE 3-4. Tyrosinemia Type I Clinical Summary Sheet
Date of Birth: __________/__________/__________ Age Diagnosed: __________/__________/__________


+ + -
Length/ Weight Head Na K Cl HCO3 P Alkaline SGOT SGPT Succinyl Transthyretin PHE TYR PHE TYR Protein Energy
Height Circum Phos acetone
(mo/d/yr) (cm) (kg) (cm) (mEq/L) (mEq/L) (mEq/L) (mEq/L (mg/dL) (U/L) (U/L) (U/L) (µmol/L) (mg/dL) (µmol/L) (µmol/L) (mg) (mg) (g) (kcal)
)
REFERENCES
1. Acosta PB: The contribution of therapy of inherited amino acid disorders to knowledge of amino acid requirements.
In Wapnir RA (ed): Congenital Metabolic Diseases: Diagnosis and Treatment. New York: Marcel Dekker Inc,
1985, pp 115-135.
2. Ameen VZ, Powell GK, Rassin DK: Cholestasis and hypermethioninemia during dietary management of hereditary
tyrosinemia type 1. J Pediatr 1986;108:949-952.
Dis 2000;23 Suppl 1:29.
4. Bain MD, Purkiss P, Jones M, et al: Dietary treatment eliminates succinylacetone from the urine of a patient with
tyrosinemia type 1. Eur J Pediatr 1990;149:637-639.
5. Balint JP, Lindstadt S, Holme E, Balistreri WF: Long-term follow-up: Treatment of acute hereditary tyrosinemia
type I without liver transplantation. J Pediatr Gastroenterol Nutr 1994;19:345A.
1996.
7. Berger R: Biochemical aspects of type I hereditary tyrosinemia. In Bickel H, et al (eds): Inherited Diseases of
Amino Acid Metabolism. New York: Thieme Inc, 1985, pp 192-202.
8. Berger R, Michals K, Galbraeth J, Matalon R: Tyrosinemia type Ib caused by maleylacetoacetate isomerase
deficiency: A new enzyme deficiency. Pediatr Res 1988;23:328A.
9. Bonkowsky HL, Magnussen CR, Collins AR, et al: Comparative effects of glycerol and dextrose on porphyrin
precursor excretion in acute intermittent porphyria. Metabolism 1976;25:405-414.
11. Cohn RM, Yudkoff M, Yost B, et al: Phenylalanine-tyrosine deficiency syndrome as a complication of the
management of hereditary tyrosinemia. Am J Clin Nutr 1977;30:209-214.
12. Dubois J, Garel L, Patriquin H,et al: Imaging features of type I hereditary tyrosinemia: A review of 30 patients.
Pediatr Radiol 1996;26:845-851.
14. Endo F, Kitano K, Uehara I, et al: Four-hydroxyphenylpyruvic acid oxidase deficiency with normal
fumarylacetoacetase: A new variant form of hereditary tyrosinemia. Pediatr Res 1983;17:92-96.
17. Haber BA, Chuang E, Lee W, Taub R: Variable gene expression within human tyrosinemia type I liver may reflect
region-specific dysplasia. Hepatology 1996;24:65-71.
20. Holme E, Lindstedt S: Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione).
J Inher Metab Dis 1998;21:507-517.
21. Holme E, Lindstedt S, Lock EA: Treatment of tyrosinemia type I with an enzyme inhibitor. Intl Pediatr
1995;10:41-43.
23. Kvittingen EA: Tyrosinemia type I: An update. J Inher Metab Dis 1991;14:554-562.
24. Kvittingen EA, Talseth T, Halvorsen S, et al: Renal failure in adult patients with hereditary tyrosinemia type I.
25. Laine J, Salo MK, Krogerus L, et al: The nephropathy of type I tyrosinemia after liver transplantation. Pediatr Res
1995;37:640-645.
26. Lindstedt S, Holme E, Lock EA, et al: Treatment of hereditary tyrosinemia type I by inhibition of
4-hydroxyphenylpyruvate dioxygenase. Lancet 1992;340:813-817.
1982.
1987;1:1-17.
29. Meites S (ed): Pediatric Clinical Chemistry: Reference Normal Values, ed 3. Washington, DC: AAAP Press, 1989.
62 Tyrosinemia Types Ia and Ib © 2001 Ross Products Division

30. Mitchell GA, Grompe M, Lambert M, Tanguay RM: Hypertyrosinemia. In Scriver CR, et al (eds): The Metabolic and
Molecular Bases of Inherited Disease, ed 8. New York, McGraw-Hill Medical Publishing Division, 2001,
pp 1777-1806.
31. Mitchell G, LaRochelle J, Lambert M, et al: Neurologic crises in hereditary tyrosinemia. N Engl J Med
1990;322:432-437.
33. Paradis K: Tyrosinemia: the Quebec experience. Clin Invest Med 1996;19:11-16.
1955;56:231-251.
36. Rank JM, Pascual-Leone A, Payne W, et al: Hematin therapy for the neurologic crisis of tyrosinemia. J Pediatr
1991;118:136-139.
37. Riudor E, Ribes A, Lloret J, et al: Liver transplantation in two children with tyrosinemia type I: Biochemical
aspects. J Inher Metab Dis 1991;14:281-284.
38. Roth KS, Carter BE, Higgins ES: Succinylacetone effects on renal tubular phosphate metabolism: A model for
experimental renal Fanconi syndrome. Proc Soc Exp Biol Med 1991;196:428-431.
Publisher, 1976.
42. Snyderman SE, Boyer A, Norton PM, et al: The essential amino acid requirements of infants. X. Methionine. Am J
Clin Nutr 1964;15:322-330.
43. Sovik O, Kvittingen EA, Steen-Johnsen J, Halvorsen S: Hereditary tyrosinemia of chronic course without rickets
and renal tubular dysfunction. Acta Paediatr Scand 1990;79:1063-1068.
1989;143:828-832.
45. Suzuki Y, Konda M, Imai I, et al: Effect of dietary treatment on the renal tubular function in a patient with
hereditary tyrosinemia. Int J Pediatr Nephrol 1987;8:171-176.
1977;30:1269-1280.

PROTOCOL 4 — Tyrosinemia Types II and III

TYREX ®-1 and TYREX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
Tyrosinemia type II is characterized by greatly elevated concentrations of blood and urine tyrosine
(TYR) and by increases in urinary phenolic acids, N-acetyltyrosine, and tyramine. Deficiency of
hepatic cytosolic tyrosine aminotransferase (TAT) has been demonstrated (Figure C). Characteristic
physical findings include stellate corneal erosions and plaques and bullous lesions of the soles and
palms. Persistent keratitis and hyperkeratosis occur on the fingers and palms of the hands and on the
soles of the feet. These skin abnormalities respond to restriction of dietary phenylalanine (PHE) and
TYR (33, 39, 43). Intracellular crystallization of TYR is thought to cause these inflammatory
responses. Mental retardation may occur (42).
Two clinical subsets of hereditary tyrosinemia type III result from dysfunction of
p-hydroxyphenylpyruvic acid dioxygenase (p-OHPPAD) (Figure C). The most severe is type IIIa with
no hepatic p-OHPPAD activity. Neurologic abnormalities, including seizures, ataxia, and mental
retardation, have been reported in untreated patients with type IIIa. Hawkinsinuria (Type IIIb) is named
for the 2-L-cysteinyl 5-1,4-dihydroxycyclohexenyl-5, 1-acetic acid which presumably is formed from an
intermediate resulting from the impaired p-OHPPAD reaction. Metabolic acidosis and failure to thrive
with a "swimming pool"-like odor are described (42). Restriction of TYR and PHE improves the critical
condition (47).
Dietary protein
Tissue protein
Phenylalanine
Tissue protein synthesis
catabolism CO2 + H2O
Melanin
Tyrosine*
Epinephrine
Thyroxine
Tyrosine aminotransferase (tyrosinemia type II)
p-Hydroxyphenylpyruvic acid*
p-OH phenylpyruvic (Tyrosinemia type III)

acid dioxygenase¹
Homogentisic acid * Accumulates in untreated

tyrosinemia types II and III
¹ Inhibited by NTBC
Maleylacetoacetic acid Enzyme malfunction
Fumarylacetoacetic acid
Fumaric acid
+
Acetoacetic acid
Figure C. Tyrosine metabolism in tyrosinemia types II and III

The PHE- and TYR-restricted diet has been successfully used in several patients, including a pregnant
woman (24), with tyrosinemia types II and III, with rapid resolution of clinical symptoms (33, 39, 43,
47).
64 Tyrosinemia Types II and III © 2001 Ross Products Division

A. The Defect
1. Tyrosinemia may result from defect in 1 of several enzymes:
a. Type Ia: Fumarylacetoacetate hydrolyase (Protocol 3, p 49).
b. Type Ib: Maleylacetoacetate isomerase (Protocol 3, p 49).
c. Type II: TAT (16, 27, 29, 33, 42).
d. Type III: p-OHPPAD (16-18, 26,42, 47).
e. Transient: p-OHPPAD immaturity (16).
1. Concentration > 4 mg/dL of TYR by bacterial inhibition assay of dried blood spot requires
differential diagnosis (16)
2. Because few states screen for tyrosinemia, infants, children, or adults with any of following
clinical findings should be evaluated for tyrosinemia type II (3, 5-7, 9, 10, 13, 15, 25, 27-29,
36, 48, 50):
a. Eye lesions.
1) Photophobia, redness, and/or lacrimation.
2) Persistent herpetiform dendritic ulcers.
3) Ulcerations and thick corneal or conjunctival plaques with neovascularization.
b. Skin lesions.
1) Hyperkeratosis of fingers, palms, toes, and/or soles of feet.
2) Blisters.
3) Erosions.
c. Seizures.
d. Mental retardation.
3. Patients with tyrosinemia type III have been reported with immunologic abnormalities (19, 20),
intermittent ataxia (26), neurologic abnormalities (42), and no symptoms (53).
C. Differential Diagnosis (42)
3. This protocol addresses nutrition support for patients with TAT or p-OHPPAD deficiency.

1. Restrict dietary PHE and TYR to amounts tolerated by patient to maintain treatment plasma
amino acid concentrations.
V. Establish Goals of Nutrition Support (3, 5-7, 9, 10, 12, 13, 15, 17-20, 22, 25-29, 33, 36, 39, 47,
48)
1. Maintain 2- to 4-hour postprandial plasma PHE and TYR concentrations in ranges noted
below, when measured by quantitative methods, or within normal range for age established by
laboratory used.
PHE 35 - 90 0.58 - 1.49
TYR 40 - 80 0.72 - 1.45
3. With plasma PHE and TYR concentrations in normal range, plasma amino acids must
be measured frequently to prevent deficiency (10).
B. Growth, Development, and Nutrition Status (11, 30, 35)
in adults.
© 2001 Ross Products Division Tyrosinemia Types II and III 65

3. Maintain normal nutrition status.
5. Maintain plasma and urine free of, or containing only traces, of N-acetyltyrosine, p-tyramine,
and parahydroxyphenyl organic acids.
C. Physical Manifestations
1. Prevent oculocutaneous and/or palmo-plantar lesions.

A. PHE Plus TYR
1. Prescribe PHE plus TYR intake that promotes goals of nutrition support.
2. PHE plus TYR requirement varies widely:
a. From patient to patient, depending on activity of TAT or p-OHPPAD.
1) Age
2) Growth rate
3) Adequacy of protein and energy intakes
4) State of health.
3. Lowest value for age for PHE plus TYR listed in Table 4-1, p 70, is suggested for initiating
therapy.
4. Changing requirements of patients are determined by frequent monitoring of :
a. Plasma PHE and TYR concentrations.
b. Plasma and urine concentrations of N-acetyltyrosine, p-tyramine, and parahydroxyphenyl
organic acids.
c. See Section IX, Suggested Evaluation of Nutrition Support, p 67.
Warning: Inadequate PHE plus TYR intake results in anorexia, lethargy, and hypotonia;
decreased growth rate in children; weight loss in adults; decreased plasma
fibrogen concentration; and increased plasma amino acid concentrations
(except PHE and TYR) (14).
B. Protein
1. Prescribe, initially, amount greater than Recommended Dietary Allowances (RDAs) (23)
(Table 4-1, p 70).
equivalent as a result of:
large part of protein is supplied by L-amino acids (31, 32).
c. Rapid catabolism of amino acids (31, 32, 34, 37, 52).
Warning: Inadequate protein intake will result in failure to thrive in infant, weight loss
in children and adults, low plasma transthyretin, osteopenia, hair loss, and
decreased PHE and TYR tolerance.
C. Energy
1. Prescribe amount that should support normal weight gain for infants and children and maintain
weight for height in adults (Table 4-1, p 70).
2. Requirements vary and may be greater than normal when L-amino acids supply majority of
protein equivalent (46, 49).
Warning: Inadequate energy intake results in failure to thrive in infants and weight loss
in children and adults with elevated plasma PHE and TYR concentrations
resulting from muscle protein catabolism.
D. Fluid

A. PHE Plus TYR
PHE and TYR source for infants because of low iron content.
2. Parents or patients may select any food in prescribed Servings Lists for PHE-Restricted Diets
B. Protein
1. Calculate amount of protein provided by infant formula with iron, beikost, whole cow's milk, or
table foods (Table 4-2, p 70) required to fill PHE plus TYR prescription.
3. Supply remaining prescribed protein with Tyrex (Table 4-2, p 70).
a. Weigh Tyrex powder on scale that reads in grams because of variability of household
b. See Table 3-3 (p 59, footnote 3) for approximate packed weight of Tyrex powder in level,
C. Energy
and Tyrex (Table 4-2, p 70) required to fill PHE plus TYR and protein prescriptions.
Energy Module with Iron, Vitamins & Minerals (Appendix 11, p A-10); sugar (48 kcal/Tbsp); or
Free Foods B (Table 4-2, p 70).
1. Add sufficient boiled, cooled water to infant formula, Tyrex, and carbohydrate to yield
prescribed volume. Tap water may replace boiled, cooled water when preparing Tyrex for
older infants, children, and adults.
2. Mix with sterilized blender at lowest speed for 3 to 4 seconds. Excess mixing may
destabilize emulsion. Medical foods may also be mixed in sterilized, tightly closed container
by shaking vigorously for 10 to 12 seconds.
3. Place in sterilized formula bottles. Cap and store in refrigerator until used. Discard unused
portion 24 hours after mixing because of nutrient loss.
before feeding.
can burn infant and steam can make bottles explode.
8. For children and adults, chill Tyrex medical food mixture to improve taste.
E. Diet Guide
each diet change.
2. Feed young infants 6 to 8 times daily (34, 37, 51).
3. Feed older infants, children, and adults 4 to 6 times daily (34, 37, 51).

Prescription, p 65.
a. See Table 4-2, p 70, for composition of Tyrex and average nutrient content of beikost or
table foods.
vitamins (Table 3-3, p 59, and Appendices 13 and 14, pp A-14 and A-15).
a. See Appendices 4 through 7, pp A-4 to A-7, for complete nutrient composition of infant
formulas and Appendix 8, p A-8, for composition of whole cow's milk.
not available.
c. If Tyrex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
supplements) (11, 30, 35).
B. Osmolarity
1. If concentration of prescribed medical food mixture is > 24 kcal/oz, determine if osmolarity is
in acceptable range.
b. Osmolarity per gram of Tyrex is listed in Appendix 19, p A-21.
adults, or greater than tolerated by patient, increase water content of prescribed medical food
mixture and recalculate its osmolarity (40, 41).
renal solute load.
b. Upper limit of renal solute load for neonates is approximately 1,100 mosm/L.
recalculate.
IX. Suggested Evaluation of Nutrition Support (16)

1. Initial.
a. Evaluate weekly by quantitative methods until 6 months of age.
2. Ongoing.
a. Evaluate monthly.
b. Frequent evaluations help ensure adherence to nutrition support plan.
3. Unacceptable PHE and TYR concentrations.
a. If plasma PHE or TYR concentration is not detected and patient has ingested full
prescription:
1) Increase prescribed amount of PHE plus TYR by 25% and reevaluate plasma
concentration in 3 to 4 days.
2) If plasma PHE or TYR concentration continues undetected, repeat above process
b. If plasma PHE concentration is < 35 µmol/L (0.58 mg/dL) or plasma TYR concentration is
< 40 µmol/L (0.72 mg/dL) and patient has ingested full prescription:
1) Increase prescribed amount of PHE plus TYR by 5% to 10% and reevaluate plasma
concentration in 7 days.

2) If plasma PHE or TYR concentration continues to be low, repeat above process until
c. If plasma PHE concentration is > 90 µmol/L (1.49 mg/dL) or plasma TYR concentration is
> 80 µmol/L (1.45 mg/dL) and patient is not ill and has not ingested more or less protein
and energy than prescribed:
1) Decrease prescribed amount of PHE plus TYR by 5% to 10% and reevaluate plasma
concentrations in 7 days.
2) If plasma PHE or TYR concentration continues to be high, repeat above process until
B. Organic Acids in Urine
1. Evaluate N-acetyltyrosine, p-tyramine, and p-hydroxyphenyl organic acids monthly or if
plasma TYR concentration is elevated.
C. Protein Status
1. Evaluate plasma transthyretin concentration at 3, 6, 9, and 12 months in infants and twice
yearly in children and adults (Appendix 17, p A-18, for standards).
concentration in 1 month. If plasma PHE and TYR concentrations are in treatment range,
use Tyrex to increase protein.
b. If plasma transthyretin concentration remains low, repeat above process until value is in
normal range.
D. Iron Status
a. Evaluate at 6, 9, and 12 months in infants and twice yearly in children and adults
(Appendix 17, p A-18, for standards).
2. Complete blood count
E. Growth Status
1. Height and weight.
a. Measure infants every 3 months and children and adults every 6 months. Plot
b. Maintain height and weight between 10th and 90th percentiles. Some normal children and
adults will fall above or below these percentiles.
2. If height or weight falls below usual growth channel:
b. If height or weight remains low, repeat above process until usual growth channel is
achieved.
F. Nutrient Intake
and 25, pp A-26 and A-27).
not available.

G. Clinical Summary
X. Sample Prescription
A. Example
Establish and fill prescription for 5-year-old weighing 20 kg who has tyrosinemia type II using
Recommended Daily Nutrient Intakes in Table 4-1, p 70, and average nutrient contents from
Table 4-2, p 70. Plasma PHE concentration is 100 µmol/L and plasma TYR is 500 µmol/L.
PHE and TYR 510 mg
Protein 35 g
Energy 1,300 kcal
Fluid 1,300 mL
Tyrex-2 93 g 0 0 27.9 381
Food List Servings

Fats 6 30 24 0.6 360
Fruits 4 60 40 2.0 240
Free Foods A 1 5 4 0.1 65
Free Foods B 1 0 0 0.0 55
Total per day 305 208 35.2 1,301

A. Rationale
1. In normal person, febrile illness and trauma are accompanied by catabolism of body
protein (54).
2. Well-nourished patients with tyrosinemia type II or III respond to infection and trauma as do
normal persons.
3. Extent of protein catabolism determines subsequent elevation in blood PHE and TYR
concentrations.

a. Enhance energy intake when possible by offering fruit juices ad libitum as tolerated; liquid
Jell-O ®; Polycose liquid or powder (Appendix 9, p A-9) added to fruit juices if tolerated;
and caffeine-free soft drinks (not diet).
b. 1/3 cup Polycose powder may be added to liquid Pedialyte to yield 8 fl oz.
c. Return patient to Tyrex medical food mixture and pre-illness diet as rapidly as possible.
1) Begin with 1/2 original strength of Tyrex medical food mixture.
2) Increase to original strength, as tolerated.

TABLE 4-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With
Tyrosinemia Types II or III
Age Nutrient
PHE 1, 2 TYR 1,2 Protein 3 Energy 3 Fluid 4
Infants
0 to < 3 mo 30 - 90 35 - 90 3.50 - 3.00 120 (145 - 95) 150-125
3 to < 6 mo 30 - 70 30 - 70 3.50 - 3.00 115 (145 - 95) 160-130
6 to < 9 mo 25 - 50 25 - 50 3.00 - 2.50 110 (135 - 80) 145-125
9 to < 12 mo 20 - 40 20 - 40 3.00 - 2.50 105 (135 - 80) 135-120
(mg/day) (mg/day) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 250 - 500 200 - 450 > 30.0 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 260 - 550 250 - 500 > 35.0 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 270 - 600 260 - 550 > 40.0 2,400 (1650 - 3300) 1,730 - 3,300
Women
11 to < 15 yr 300 - 650 290 - 500 > 50.0 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 280 - 700 270 - 450 > 55.0 2,100 (1200 - 3000) 1,200 - 3,000
> 19 yr 270 - 700 260 - 450 > 60.0 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 275 - 700 260 - 550 > 55.0 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 350 - 750 340 - 550 > 65.0 2,800 (2100 - 3900) 2,100 - 3,900
> 19 yr 340 - 750 330 - 550 > 70.0 2,900 (2000 - 3300) 2,000 - 3,300
1
Initiate therapy with lowest value for age range. Modify prescription based on frequently obtained plasma values and
growth in infants and children and frequently obtained plasma values and weight maintenance in adults.
2
From references 1, 2, 16, 38, 49.
3
From references 21, 23.
4
From reference 8. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid to
1
TABLE 4-2. Serving Lists for PHE- and TYR-Restricted Diets: Average Nutrient Content per Serving
Food List Nutrient

Fats 5 4 0.1 60
Fruits 15 10 0.5 60
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 86 29 1.86 68
2
2
Isomil ® Soy Formula With Iron, Ready to Feed, 100 mL 88 60 1.66 68
2
Tyrex®-1 0 0 15.00 480
Tyrex®-2 0 0 30.00 410
3
1
From reference 16.
2
3

TABLE 4-3. Tyrosinemia Types II and III Clinical Summary Sheet

Date of Birth: __________/__________/__________

Mo Day Year

2 3
Length/ Weight Head Hgb Ferritin Transthyretin Urine PHE TYR PHE TYR Protein Energy
1
Height Circum p-OHPOA
(mo/d/yr) (yrs/mos) (cm) (kg) (cm) (g/dL) (ng/mL) (mg/dL) (mg) (mg) (g) (kcal)
Tyrosinemia Types II and III 71
1
Urine p-hydroxyphenyl organic acids.
2
REFERENCES
1985, 115-135.
3. Al-Hemidan A, Al-Hazzaa SAF: Richner-Hanhart syndrome (tyrosinemia type II). Ophthal Genet 1995;16:21-26.
Dis 2000;23 (Suppl 1):29A.
5. Balato N, Cusano F, Lembo G, Santoianni P: Tyrosinemia type II in two cases previously reported as Richner-
Hanhart syndrome. Dermatologica 1986;173:66-74.
6. Bardelli AM, Borgogni P, Farnetani MA, et al: Familial tyrosinemia with eye and skin lesions. Opthalmologica
(Basel) 1977;175:5-9.
7. Barr DGB, Kirk JM, Laing SC: Outcome in tyrosinaemia type II. Arch Dis Child 1991;66:1249-1250.
1996.
9. Benoldi D, Orsoni JB, Allegra F: Tyrosinemia type II: A challenge for ophthalmologists and dermatologists. Pediatr
Dermat 1997;14:110-112.
10. Billson FA, Danks DM: Corneal and skin changes in tyrosinemia. Aust J Opthalmol 1975;3:112-115.
12. Cerone R, Holme E, Schiaffino MC, et al: Tyrosinemia type III: Diagnosis and ten-year follow-up. Acta Paediatr
1997;86:1013-1015.
13. Charlton KH, Binder PS, Wozniak L, Digby DJ: Pseudodendritic dermatitis and systemic tyrosinemia.
Ophthalmology 1981;88:355-360.
14. Cohn RM, Yudkoff M, Yost B, et al: Phenylalanine-tyrosine deficiency syndrome as a complication of the
management of hereditary tyrosinemia. Am J Clin Nutr 1977;30:209-214.
15. Colditz PB, Yu JS, Billson FA, et al: Tyrosinemia II. Med J Aust 1984;141:244-245.
17. Endo F, Awata H, Tanoue A, et al: Tyrosinaemia type III: Immunochemical studies on 4-hydroxyphenylpyruvic acid
dioxygenase and molecular cloning of cDNA for the enzyme. J Inher Metab Dis 1991;14:783-786.
18. Endo F, Kitano K, Uehara I, et al: Four-hydroxy-phenylpyruvic acid oxidase deficiency with normal
fumarylacetoacetase: A new variant form of hereditary tyrosinemia. Pediatr Res 1983;17:92-96.
19. D'Eufemia P, Finocchiaro R, Celli M, et al: Immunological abnormalities in a patient with tyrosinemia type II.
20. D'Eufemia P, Giardini O, Cantani F, et al: Autoimmune thyroiditis in a case of tyrosinemia type II. J Inher Metab
Dis 1992;15:861-862.
1985.
22. Faull KF, Gan I, Halpern B, et al: Metabolic studies on two patients with nonhepatic tyrosinemia using deuterated
tyrosine loads. Pediatr Res 1977;11:631-637.
24. Francis DEM, Kirby DM, Thompson GN: Maternal tyrosinemia type II: Management and successful outcome. Eur J
Pediatr 1992;151:196-199.
25. Garibaldi IR, Siliato F, DeMartini I, et al: Oculocutaneous tyrosinosis. Helv Paediatr Acta 1977;32:173-180.
26. Giardini O, Cantani A, Kennaway NG, D'eufemia P: Chronic tyrosinemia associated with 4-hydroxy-phenylpyruvate
dioxygenase deficiency with acute intermittent ataxia and without visceral and bone involvement. Pediatr Res
1983;17:25-29.
27. Goldsmith LA: Tyrosinemia II: Lessons in molecular pathophysiology. Pediatr Dermatol 1983;1:25-34.
28. Goldsmith LA, Reed J: Tyrosine-induced eye and skin lesions. JAMA 1976;236:382-384.
29. Goldsmith LA, Thorpe J, Roe CR: Hepatic enzymes of tyrosine metabolism in tyrosinemia II. J Invest Dermatol
1979;73:530-532.
30. Greeves LG, Carson DJ, Craig BG, McMaster D: Potentially life-threatening cardiac dysrhythmia in a child with
selenium deficiency and phenylketonuria. Acta Paediatr Scand 1990;79:1259-1262.

33. Halvorsen S, Skjelkvale L: Tyrosine aminotransferase deficiency (TATD): First case diagnosed on newborn
screening and successfully treated with PHE-TYR restricted diet from early age. Pediatr Res 1977;11:1017A.
36. Hunziker N: Richner-Hanhart syndrome and tyrosinemia type II. Dermatologica 1980;160:180-189.
38. Leverton RM, Johnson N, Dazur J, Ellison J: Amino acid requirements of young adults. In Albanese AA (ed):
Protein and Amino Acid Nutrition. New York: Academic Press, 1959.
39. Machino H, Miki Y, Kawatsu T, et al: Successful dietary control of tyrosinemia II. Am Acad Dermatol
1983;9:533-539.
1982.
1987;1:1-17.
42. Mitchell GA, Grompe M, Lambert M, Tanguay RM: Hypertyrosinemia. In Scriver CR, et al (eds): The Metabolic and
Molecular Bases of Inherited Disease, ed 8. New York, McGraw-Hill Medical Publishing Division, 2001,
pp 1777-1806.
43. Ney D, Bay C, Schneider JA, et al: Dietary management of oculocutaneous tyrosinemia in an 11-year-old child.
Am J Dis Child 1983;137:995-1000.
1955;56:231-251.
47. Preece MA, Rylance GW, MacDonald A, et al: A new case of tyrosinaemia type III detected by neonatal screening.
J Inher Metab Dis 1996;19 (Suppl 1):32.
48. Rabinowitz LG, Williams LR, Anderson CE, et al: Painful keratoderma and photophobia: Hallmarks of tyrosinemia
type II. J Pediatr 1995;126;266-269.
49. Rose WC, Wixom RL: The amino acid requirements of man. XIV. The sparing effect of tyrosine on the
phenylalanine requirement. J Biol Chem 1955;217:95-101.
50. Sandberg HO: Bilateral keratopathy and tyrosinosis. Acta Ophthalmol 1975;53:760-764.
53. Stoppoloni, G, Santinelli R, Priscof, et al: Benign tyrosinemia: An 18-year follow-up. J Inher Metab Dis
1995;18:641-642.
1977;30:1269-1280.

PROTOCOL 5 — Maple Syrup Urine Disease (MSUD)

KETONEX ®-1 and KETONEX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
The branched-chain amino acids (BCAAs) isoleucine (ILE), leucine (LEU), and valine (VAL) are
essential nutrients. In newborns, 75% of BCAAs ingested are used for protein synthesis. Those
present in excess of need for synthetic purposes are degraded through many steps to provide energy
(Figure D). The initial step in catabolism is reversible transamination, requiring a specific
transaminase and the coenzyme pyridoxal phosphate. The second step is irreversible oxidative
decarboxylation which uses the branched-chain-α-ketoacid dehydrogenase (BCKAD) complex. This
complex is located in the inner mitochondrial membrane and requires the coenzymes thiamin
pyrophosphate, lipoic acid, CoA, and NAD+ (36). The Figure below schematizes this overall reaction,
which is impaired in maple syrup urine disease (MSUD) (8).
Dietary protein Dietary protein Dietary protein

Tissue protein catabolism Tissue protein catabolism Tissue protein catabolism
Branched-chain amino acids

Leucine * Isoleucine * Valine *
Tissue Tissue
protein protein
synthesis synthesis
α-Ketoacids α-Ketoisocaproic acid * α-Keto-3-methylvaleric acid * α-Ketoisovaleric acid *
Thiamin Thiamin Thiamin

Branched-chain α-ketoacid
(4n) (4n) (4n)
dehydrogenase complex
Acetyl-CoA Acetyl-coA Propionyl-CoA

+ + (n)
Acetoacetate Propionyl-CoA
Enzyme defect (n) Succinyl-CoA
(n) = several steps
* Accumulates in the body in Succinyl-CoA
untreated MSUD.
Figure D. Branched-chain amino acid metabolism in maple syrup urine disease

When thiamin pyrophosphate saturates its site on BCKAD, biologic turnover of BCKAD is decreased
because the multienzyme complex undergoes a conformational change, making it more resistant to
chymotrypsin and heat degradation. The biologic half-life of the enzyme and overall activity are
increased when a new equilibrium of enzyme synthesis and degradation is reached (11, 12).
MSUD is a group of inherited disorders of ILE, LEU, and VAL metabolism (8, 11) resulting from
several mutations that impair various components of the multienzyme BCKAD (Figure D). An
autosomal recessive mode of inheritance is defined for all reported cases. The incidence of MSUD is
approximately 1/100,000 to 1/300,000 live births in the general population, and 1/760 live births in the
Mennonite population (8, 11).
Infants with MSUD appear normal at birth and are clinically well until after eating a protein-containing
feed. The most severely impaired enzymes may produce seizures, apnea, and death within 10 days of
birth. The disorder is characterized by elevated blood, urine, and cerebrospinal fluid concentrations of
the branched-chain-ketoacids (BCKAs), their amino acid precursors, and alloisoleucine (ALLO).
Progressive neurologic dysfunction and production of urine with the odor of maple syrup follow. The
sweet smell may only be evident in earwax, sensed after otoscopic
© 2001 Ross Products Division Maple Syrup Urine Disease 75

examination. Neurologic impairment in the newborn is manifested by poor sucking, irregular respiration,
rigidity alternating with flaccidity, opisthotonos, progressive loss of Moro reflex, and seizures (8, 11).
Immune suppression may occur as a result of elevated plasma organic acid concentrations (53).
Several variants with a spectrum of impaired mitochondrial BCKAD complex have been reported.
Clinical manifestations are expressed intermittently upon protein loading or with febrile illness in
patients with partial enzyme activity between 5% and 30% of normal. A thiamin-responsive form with
expression similar to the intermediate form has been described (8, 11).
Untreated patients with classic MSUD (0-2% BCKAD activity) who survive beyond early infancy
have retarded physical and mental development (8, 11). If death occurs within the 1st few days of life,
few unique abnormalities are seen in the brain. With prolonged survival, deficient myelination is
thought to be due to inhibition of enzymes involved in myelin formation, inhibition of amino acid
transport, and inhibition by BCKAs of oxidative phosphorylation (8, 11). Early diagnosis and adequate
nutrition support lead to normal growth and development.

Patients diagnosed ≤ 5 days of age had an IQ (97 ± 13 SD) greater than that of normal siblings or
parents (24). Factors influencing IQ were age at diagnosis, neonatal condition, and long-term
metabolic control (32). Reproductive outcome of a woman with classic MSUD whose blood BCAAs
were controlled by diet was excellent (52).
The first attempt to manage an 8-month old infant with MSUD used pure amino acids totaling
approximately 50 g daily and 1,500 kcal/day. Mineral and vitamin mixtures were also provided.
Plasma concentrations of BCAAs decreased significantly. During the course of the diet trial, length
and weight increased from the 3rd percentile to the 50th percentile (2).
Nutrition support of a neonate with MSUD was subsequently described (2). Protein intake ranged
from 3.5-3.0 g/kg/day between 3 and 8 months of age. Energy intake was about 125 kcal/kg/day. At
birth, the infant was at the 10th percentile for length and weight; during the 1st year of life, length
increased toward the 50th percentile but weight remained at about the 10th percentile. At 55 weeks of
age, the patient had a developmental quotient of 97, which is in the normal range (2).
A number of investigators have reported poor growth in treated children with MSUD (2). Intakes of
both protein and energy by children with MSUD have been reported to be below that of comparable
aged normal children (19) and below RDA (15). Whether failure to thrive is due to the underlying
disease or to dietary deficiency is unclear. However, some investigators reported normal growth in
patients fed adequate protein and energy (2).
Selenium deficiency has been found in treated patients with MSUD who received selenium-free
medical foods (21, 28). B-vitamin deficiencies resulting in anemia, angular stomatitis, and lesions of
the skin occurred in one baby when the B-vitamin mixture was not added to the diet for 6 weeks (2).
Folic acid deficiency was reported in an infant after about 4 months on a synthetic diet (2). Metabolic
acidosis occurred in an infant treated with an amino acid mix in which several amino acids were
provided as the HCl salt (2).

A. The Defect
1. MSUD may result from 1 of several defects in the BCKAD complex.
1. Concentration ≥ 4 mg LEU/dL by bacterial inhibition assay requires differential diagnosis (11).
2. Infants who develop poor suck, shrill cry, lethargy, and vomiting; followed by loss of normal
tendon reflexes, alternating periods of hypertonia and hypotonia, seizures, loss of
consciousness, irregular respiration, apnea, metabolic acidosis, or maple syrup odor in warm
urine or ear wax should be evaluated (44).
C. Vitamin Responsive
1. Evaluate thiamin responsiveness in patients with any BCKAD complex activity.
2. Prescribe 100-500 mg oral thiamin per day for up to 3 months (8, 14).
76 Maple Syrup Urine Disease © 2001 Ross Products Division

1. Restrict dietary BCAAs (ILE, LEU, and VAL) to amounts tolerated by patient to maintain
treatment plasma amino acid concentrations.
B. Stabilize Altered Enzyme Protein
1. Supplement with oral thiamin if patient has any BCKAD activity (12, 14).
V. Nutrition Support During Acute Illness or at Diagnosis (20, 53-55)

A. Initiation of Nutrition Support
1. Initiate nutrition support immediately. Do not wait for confirmation of diagnosis.
2. Evaluate plasma concentrations of ILE, LEU, and VAL daily.
B. Patients Without Severe Neurologic Involvement
1. Begin high-energy feeds (120-150 kcal/kg for infants, 80-100 kcal/kg for children, and
40-50 kcal/kg for adults) that supply adequate water (Table 5-1, p 85) (11, 50).
a. Depending on clinical status, feed patient by nipple, nasogastric tube, intravenous
infusion, or combine these methods (44, 45).
1) For nipple or nasogastric feeds, use Ketonex (Table 5-2, p 86).
2) For intravenous feeds via central line, use hypertonic D-glucose and Liposyn ® II
3) For intravenous feeds via peripheral line, use isotonic glucose and Liposyn II
2. Introduce nutrition support with Ketonex as rapidly as possible.
a. See Table 5-1, p 85, for Recommended Protein, Energy, and Fluid Intakes.
b. See Table 5-2, p 86, for composition of Ketonex.
Warning: Add L-ILE to Ketonex feeds when plasma ILE concentration reaches upper
limit of treatment range (105 µmol/L), usually within 1-3 days of starting
nutrition support (45). Plasma LEU concentrations will NOT decrease to
normal range if intake of either ILE or VAL is deficient.
c. Order L-ILE and L-VAL immediately when nutrition support is initiated.
d. See Table 5-1, p 85, for Recommended ILE Intakes and Appendix 26, p A-28, for source
of L-ILE.
e. Mix weighed amount of L-ILE powder with boiled, cooled water to make known volume
that supplies 10 mg/mL (eg, 1 g L-ILE with enough water to yield 100 mL).
f. Refrigerate in closed container until used. Discard unused mixture after 1 week, if not
frozen.
g. Measure into Ketonex medical food mixture with disposable syringe.
Warning: Patient will develop severe skin and eye lesions if ILE deficiency occurs (16,
26, 33, 51).
3. Add L-VAL (Table 5-1, p 85) to Ketonex feeds when plasma VAL concentration reaches upper
limit of treatment range (318 µmol/L), usually within 2 to 4 days of starting nutrition
support (45).
a. Mix weighed amount of L-VAL powder (Appendix 26, p A-28) with boiled, cooled water to
make known volume that supplies 10 mg/mL (1 g L-VAL powder with enough water to
yield 100 mL).
b. Refrigerate in closed container until used. Discard unused mixture after 1 week, if not
frozen.
c. Measure into Ketonex medical food mixture with disposable syringe.
4. Add LEU (Table 5-1, p 85) to Ketonex feeds when plasma LEU concentration reaches upper
limit of treatment range (185 µmol/L). May require 7-10 days if L-ILE and L-VAL are
supplemented as noted in steps 3 and 4 above (44, 45).
Warning: LEU, the last amino acid to become normal in plasma, remains elevated for
prolonged period if ILE and/or VAL are deficient (10).
a. Use infant formula with iron or whole cow's milk (Table 5-3, p 87), depending on age, to fill
LEU prescription.
1) Determine amounts of ILE and VAL in infant formula or whole cow's milk required to
supply LEU.
2) Decrease volumes of L-ILE and L-VAL solutions added to medical food mixture by
amount of ILE and VAL in infant formula or whole cow's milk.
3) Use disposable syringe to measure liquid infant formula or whole cow's milk. Weigh
powdered infant formula on scale that reads in grams.
C. Comatose Patients (10, 11)
1. See References 54 and 55 for medical management.
2. Begin BCAA-free parenteral (6) or nasogastric feeding of amino acids and energy within 36 to
48 hours of initiation of dialysis using nitrogen-free (amino acid-free) dialysate.
a. See Table 5-1, p 85, for Recommended Protein and Energy Intakes
b. See Table 5-2, p 86, for Ketonex composition.
3. Begin intravenous infusion of Liposyn II (Appendix 26, p A-28) and 10% D-glucose during
nasogastric feeding, continuing until major neurologic signs subside.
4. When plasma ILE concentration reaches upper limit of treatment range (105 µmol/L), usually
within 1 to 3 days of starting nutrition support, add L-ILE (Table 5-1, p 85) to Ketonex feeds.
a. See Section VB2, p 76.
5. When plasma VAL concentration reaches upper limit of treatment range (318 µmol/L), usually
within 2 to 4 days of starting nutrition support, add L-VAL (Table 5-1, p 85) to Ketonex feeds.
6. When plasma LEU concentration reaches upper limit of treatment range (185 µmol/L), add
LEU (Table 5-1, p 85) to Ketonex feeds.
VI. Establish Goals of Long-Term Nutrition Support

A. Plasma Amino Acid Concentrations
1. Maintain 2- to 4-hour postprandial (40) plasma concentrations of alanine (ALA), ALLO, and
BCAAs in ranges noted below when measured by quantitative methods (modified from
reference 11), or within normal range for age established by laboratory used.
ALA 275 - 450 2.4 - 4.0
ALLO 0-0 0.0 - 0.0
ILE 50 - 105 0.6 - 1.4
LEU 50 - 185 0.6 - 2.4
VAL 130 - 318 1.5 - 3.7
1. Support normal growth rates in infants and children and maintain appropriate weight for height
in adults.
3. Maintain normal nutrition status (7, 21, 28).
5. Maintain urine free of branched-chain-ketoacids.
VII. Establish Prescription for Long-Term Nutrition Support

A. ILE, LEU, and VAL (1, 9, 13, 25, 27, 46-48)
1. Prescribe intakes that promote goals of nutrition support.
2. ILE, LEU, and VAL requirements vary widely:
a. From patient to patient, depending on activity of BCKAD complex.
1) Age.
2) Growth rate.
4) State of health.

3. Lowest values for ILE, LEU, and VAL for each age group listed in Table 5-1, p 85, are
suggested for initiating therapy.
4. Changing requirements of patient are determined by frequent monitoring of:
a. Plasma ILE, LEU, and VAL concentrations.
b. Urine concentrations of branched-chain α-ketoacids.
c. See Section X, Suggested Evaluation of Nutrition Support, p 80.
d. With ILE, LEU, and VAL concentrations in normal range, plasma amino acids must be
measured frequently to prevent deficiency.
Warning: ILE, LEU, and VAL deficiencies result in the following adverse effects:
ILE deficiency (16, 26, 46, 51): Weight loss or no weight gain; redness of
buccal mucosa; fissures at corners of mouth; tremors of extremities;
decreased plasma cholesterol and ILE concentrations; increased plasma
lysine, phenylalanine, serine, tyrosine, and VAL concentrations; and skin
desquamation.
LEU deficiency (48): Loss of appetite, apathy, irritability; weight loss or poor
weight gain; decreased plasma LEU concentration; and increased plasma
ILE, methionine, serine, threonine, and VAL concentrations.
VAL deficiency (47): Poor appetite, drowsiness; excess irritability and crying
in infants; weight loss or decrease in weight gain; and decreased plasma
albumin concentration.
Prolonged exclusion, over-restriction, or imbalance of BCAAs result in
adverse effects (31): Anemia, desquamation of skin, diarrhea, and failure
to thrive in infants.
B. Protein
(Table 5-1, p 85).
c. Rapid catabolism of amino acids (17, 22, 23, 39, 42).
poor growth in children, weight loss in adults, low plasma albumin and
transthyretin concentrations, osteopenia, and hair loss.
3. Adequate protein intake that supports normal growth results in greater tolerance to restricted
BCAAs (3).
C. Energy
3. At diagnosis and during metabolic acidosis resulting from infection, energy needs may be 25%
to 40% higher than values listed in Table 5-1, p 85.
Warning: Inadequate energy intake may result in failure to thrive in infants, poor growth
in children, weight loss in adults, depressed tolerance of BCAAs, and
increased concentrations of plasma BCAAs.
D. Fluid

A. LEU
(Table 5-3, p 87) required to fill LEU prescription.
BCAA source for infants because of low iron content.
2. Measure liquid infant formula and whole cow's milk with disposable syringe. Weigh powdered
3. Add beikost or table foods to gradually displace LEU provided by infant formula after infant is
3 to 4 months old or is developmentally ready.
4. Parents or patients may select any food in prescribed food lists (Table 5-4, p 88) in specified
amounts to fill LEU prescription.
B. ILE and VAL
1. Calculate approximate amounts of ILE and VAL provided by infant formula with iron, beikost,
whole cow's milk, or table foods (Table 5-3, p 87).
2. Subtract amount determined in step B1 from total ILE and VAL prescriptions.
3. Supply any remaining prescribed ILE and VAL as individual pure solutions. If plasma
concentrations of ILE and VAL are in normal range, supplements are not required
a. Mix weighed amounts of L-ILE and L-VAL powders with boiled, cooled water to make
known volume of each that supplies 10 mg/mL (eg, 1 g with enough water to yield 100 mL).
b. Refrigerate solutions in separate, closed containers until used. Discard unused
suspensions after 1 week, if not frozen.
c. Measure solutions into medical food mixture with disposable syringe.
C. Protein
1. Calculate amount provided by infant formula with iron, beikost, whole cow's milk, or table
foods (Table 5-3, p 87) required to fill LEU prescription.
2. Subtract amount determined in step C1 from total protein prescription.
3. Supply any remaining prescribed protein with Ketonex (Table 5-2, p 87).
a. Ketonex-1 is for infants and toddlers and Ketonex-2 is for children, adolescents, and adults.
b. Weigh Ketonex powder on scale that reads in grams because of variability of household
c. See Table 5-2 (p 86, footnote 3) for approximate packed weight of Ketonex powder in
D. Energy
1. Calculate energy provided by Ketonex (Table 5-2, p 86) and infant formula with iron, beikost,
whole cow's milk, or table foods (Table 5-3, p 87) required to fill LEU and protein prescriptions.
2. Subtract amount determined in step D1 from total energy prescription.
3. Provide any remaining prescribed energy with Polycose ® Glucose Polymers powder
1. Add sufficient boiled, cooled water to infant formula, Ketonex, and carbohydrate (if needed) to
yield prescribed volume. Tap water may replace boiled, cooled water when preparing Ketonex
for older infants, children, and adults.
before feeding.
8. For children and adults, chill Ketonex medical food mixture to improve taste.
F. Diet Guide
each diet change.

Prescription for Long-Term Nutrition Support, p 77.
2. Check diet to determine if it supplies Recommended Dietary Intakes (RDIs) of minerals and
a. See Table 5-2, p 86, for composition of Ketonex and Appendices 4 through 7, pp A-4 to
A-7, for complete nutrient composition of infant formulas.
not available.
c. If Ketonex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
foods and laboratory test results indicate need. See Appendix 11, p A-10, for composition
of supplements.
B. Osmolarity
b. Osmolarity per gram of Ketonex is listed in Appendix 19, p A-21.
renal solute load.
recalculate.

A. Plasma ALA, ALLO, and BCAAs (40)
1. Initial.
a. Evaluate daily by quantitative methods until plasma concentrations stabilize and
approximate BCAA requirements are known.

2. Ongoing.
a. Use bacterial inhibition assay for blood LEU evaluation - from state laboratory if available.
b. Evaluate blood LEU concentration twice weekly by bacterial inhibition assay and twice
monthly by quantitative methods until patient is 6 months old.
c. From 6 months onward, evaluate blood LEU concentration weekly by bacterial inhibition
assay and monthly by quantitative method.
3. Unacceptable amino acid concentrations.
a. If plasma ILE, LEU, or VAL concentration is not detected and patient has ingested full
prescription:
plasma concentrations in 3 days.
2) If plasma ILE, LEU, or VAL concentration continues undetected, repeat above process
b. If plasma ILE concentration is < 50 µmol/L, plasma LEU concentration is < 50 µmol/L, or
plasma VAL concentration is < 95 µmol/L, and patient has ingested full prescription:
1) Increase prescribed amount for amino acid(s) that is low by 5% to 10% and
reevaluate plasma concentration in 1 week.
2) If plasma ILE, LEU, or VAL concentration continues low, repeat above process until
amino acid(s) concentration is in treatment range.
c. If plasma ILE concentration is > 105 µmol/L, plasma LEU concentration is > 185 µmol/L,
or plasma VAL concentration is > 318 µmol/L, and patient is not ill and has not ingested
more or less protein and energy than prescribed:
1) Decrease prescribed amount of elevated amino acid(s) by 5% to 10% and reevaluate
plasma BCAA concentrations in 1 week.
2) If plasma ILE, LEU, or VAL concentration continues high, repeat above process until
amino acid(s) concentration is in treatment range.
B. Urine Ketoacids by Ketostix ® or Dinitrophenylhydrazine (DNPH)
1. Evaluate once daily to 6 months of age and twice weekly thereafter.
2. If patient is ill, evaluate daily.
3. Urine should be free of ketoacids at all times (negative Ketostix or DNPH result).
4. If urine contains ketoacids (positive Ketostix or DNPH result):
a. Immediately obtain blood sample for evaluation of LEU by bacterial inhibition assay or
evaluation of BCAAs by quantitative methods.
b. Brief metabolic physician immediately on patient's illness.
C. Protein Status
1. Evaluate plasma transthyretin concentration every 3 months until 1 year of age and twice
yearly thereafter (Appendix 17, p A-18, for standards).
concentration in 1 month. If ILE, LEU and VAL concentrations are in treatment range, use
Ketonex to increase protein.
D. Iron Status
1) Increase iron intake to 4 mg/kg of body weight with supplements (ferrous sulfate).

2. Complete blood count and differential.
a. Hemoglobin and hematocrit concentrations and differential should be evaluated at 6, 9,
and 12 months of age and every 6 months thereafter (Appendix 17, p A-18, for
standards).
E. Growth Status
a. Measure monthly to 1 year and every 3 months thereafter until final growth is achieved.
a. Increase protein and energy prescriptions by 5% to 10% and remeasure after 1 month.
achieved.
F. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of BCAAs, protein, and energy before each blood test.
a. See Table 5-2, p 86, for composition of Ketonex and Appendices 4 through 7, pp A-4 to
not available.
c. See Appendix 28, p A-29, for information about ordering software for diet evaluation.
G. Clinical Summary

A. Example 1
Intakes from Table 5-1, p 85, and nutrient contents from Tables 5-2 and 5-3, pp 86 and 87.
ILE 60 mg/kg x 3.3 kg = 198 mg
LEU 80 mg/kg x 3.3 kg = 264 mg
VAL 70 mg/kg x 3.3 kg = 231 mg
Medical Food Mixture Measure ILE LEU VAL Protein Energy
(mg) (mg) (mg) (g) (kcal)
Ketonex-1 60.0 g 0 0 0 9.0 288
Similac With Iron RTF 183.0 mL 137 264 152 2.6 124
ILE solution1 6.1 mL 61 0 0 0.0 0
VAL solution1 7.9 mL 0 0 79 0.0 0
Polycose Liquid 25.0 mL 0 0 0 0.0 50
Total per day 198 264 231 11.6 462

Total per kg 60 80 70 3.5 140
Approximate osmolarity of medical food mixture is < 400 mosm/L. Estimated potential renal solute load
is < 100 mosm.
1
Solution is 10 mg/mL.

B. Example 2
Nutrient Intakes from Table 5-1, p 85, and nutrient contents from Tables 5-2 and 5-3, pp 86 and 87.
ILE 325 mg/day
LEU 535 mg
VAL 400 mg
Protein 30 g
Energy 1,300 kcal
Fluid 1,300 mL
Ketonex-2 71 g 0 0 0 21.3 291
1
ILE solution 1 mL 10 0 0 0.0 0
Food List Servings

Breads/Cereals 9 162 315 225 4.5 270
Fats 6 42 60 42 0.6 420
Fruits 4 68 100 88 2.4 300
Vegetables 2 44 60 48 1.2 30
Total per day 326 535 403 30.0 1,311
1
C. Example 3
Establish and fill prescription for 15-year-old boy weighing 60 kg using Recommended Daily
Nutrient Intakes from Table 5-1, p 85 , and nutrient contents from Tables 5-2 and 5-3, pp 86 and
87.
ILE 330 mg/day
LEU 550 mg
VAL 410 mg
Protein 55 g
Energy 2,800 kcal
Fluid 2,800 mL

Ketonex-2 155 g 0 0 0 46.5 708
Sugar 96 g (1/2 cup) 0 0 0 0.0 384
ILE solution 1 1.5 mL 15 0 0 0.0 0
VAL solution 1 1.4 mL 0 0 14 0.0 0
Food List Servings

Breads/Cereals 9 162 315 225 4.5 270
Fats 9 63 90 63 0.9 630
Fruits 2 34 50 44 1.2 150
Vegetables 2 44 60 48 1.2 30
Free Foods A 4 12 20 16 0.4 200
Free Foods B 8 0 0 0 0.0 440
Total per day 326 550 410 54.7 2,812
Approximate osmolarity of medical food mixture is < 1,000 mosm/L.

A. Rationale
1. In normal persons, febrile illness and trauma are accompanied by catabolism of body protein.
2. Well-nourished patients with MSUD respond to infection and trauma as do normal persons.
3. Febrile illnesses and trauma are life-threatening if not diagnosed and treated promptly.
B. Management of Nutrition Support
1. See Section V, Nutrition Support During Acute Illness or at Diagnosis, p 76.

TABLE 5-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With MSUD
Age Nutrient
1,2 1 1,3
ILE LEU VAL Protein 4 Energy 4 Fluid 5
(mg/kg) (mg/kg) (mg/kg) (g/kg) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 36 - 60 60 - 100 42 - 70 3.50 - 3.00 120 (145 - 95) 150 - 125
3 to < 6 mo 30 - 50 50 - 85 35 - 60 3.50 - 3.00 115 (145 - 95) 160 - 130
6 to < 9 mo 25 - 40 40 - 70 28 - 50 3.00 - 2.50 110 (135 - 80) 145 - 125
9 to < 12 mo 18 - 33 30 - 55 21 - 38 3.00 - 2.50 105 (135 - 80) 135 - 120
(mg/day) (mg/day) (mg/day) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 165 - 325 275 - 535 190 - 400 ≥ 30.0 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 215 - 420 360 - 695 250 - 490 ≥ 35.0 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 245 - 470 410 - 785 285 - 550 ≥ 40.0 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 330 - 445 550 - 740 385 - 520 ≥ 50.0 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 330 - 445 550 - 740 385 - 520 ≥ 55.0 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr 300 - 450 400 - 620 420 - 650 ≥ 60.0 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 325 - 435 540 - 720 375 - 505 ≥ 55.0 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 425 - 570 705 - 945 495 - 665 ≥ 65.0 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr 575 - 700 800 - 1100 560 - 800 ≥ 70.0 2,900 (2000 - 3300) 2,000 - 3,300
1
From references 1, 2, 9, 11, 25, 27, 35. Initiate prescription as noted in Section V, p 76. After 2 to 3 days of BCAA-
free feeds, begin diet with lowest recommended intake for age. Modify prescription based on frequently obtained
plasma values and growth in infants and children and frequently obtained plasma values and weight maintenance in
adults.
2
In general, ILE should be approximately 60% of LEU prescription.
3
In general, VAL should be approximately 70% of LEU prescription.
4
From reference 15.
5
children and adults for each kcal ingested. Fluid intake should be higher during illness to enhance urinary ketoacid
excretion.

TABLE 5-2. Nutrient Composition of KETONEX ®-1 1, 3 and KETONEX ®-2 2, 3,
Nutrient Ketonex-1 Ketonex-2
Energy, kcal 480 32 410 13.7
Protein equiv, g 15.00 1.000 30.00 1.000
Nitrogen, g 2.40 0.160 4.80 0.160
Amino acids, g 14.45 0.963 28.90 0.963
Cystine, g 0.15 0.010 0.30 0.010
Histidine, g 0.42 0.028 0.84 0.028
Isoleucine, g trace 0.000 trace 0.000
Leucine, g trace 0.000 trace 0.000
Lysine, g 1.00 0.067 2.00 0.067
Methionine, g 0.30 0.020 0.60 0.020
Phenylalanine, g 0.88 0.059 1.76 0.059
Threonine, g 0.70 0.047 1.40 0.047
Tryptophan, g 0.17 0.011 0.34 0.011
Tyrosine, g 0.89 0.059 1.78 0.059
Valine, g trace 0.000 trace 0.000
Carnitine, mg 100 6.67 200 6.67
Taurine, mg 40 2.67 50 1.67
Carbohydrate, g 53.0 3.53 35 1.17
Fat, g 21.7 1.45 14 0.47
4 5
Linoleic acid, g 2.00 0.133 1.50 0.050
6 7
0.36 0.024 0.17 0.006
Minerals
Calcium, mg 575 38 880 29
Chloride, mg/mEq 325/9.17 21.7/0.61 940/26.51 31.33/0.88
Chromium, µg 11 0.73 27 0.90
Copper, mg 1.10 0.073 1.00 0.033
Iodine, µg 65 4.33 100 3.33
Iron, mg 9.0 0.60 13 0.43
Magnesium, mg 50 3.33 225 7.50
Manganese, mg 0.50 0.033 0.80 0.027
Potassium, mg/mEq 675/17.26 45/1.15 1,370/35.04 45.7/1.17
Selenium, µg 20 1.33 35 1.17
Sodium, mg/mEq 190/8.26 12.7/0.55 880/38.28 29.3/1.28
Zinc, mg 8.0 0.53 13 0.43
Vitamins
A, µg RE 420 28 660 22
D, µg 7.50 0.50 7.50 0.25
E, mg α-TE 10.10 0.67 12.10 0.40
K, µg 50 3.33 60 2.00
Biotin, µg 65 4.33 100 3.33
B6, mg 0.75 0.050 1.30 0.043
B12, µg 4.90 0.327 5.00 0.167
Choline, mg 80 5.33 100 3.33
Folate, µg 230 15 450 15
Inositol, mg 40 2.67 70 2.33
Niacin equiv, mg 12.80 0.850 21.7 0.72
Riboflavin, mg 0.90 0.060 1.80 0.060
Thiamin, mg 1.90 0.127 3.25 0.108
1 2
3
Approximate packed weight of Ketonex in level, dry US standard household measures:
Ketonex-1 Ketonex-2
1 Tbsp = 7g 8g
1/4 cup = 26 g 32 g
1/3 cup = 35 g 41 g
1/2 cup = 53 g 61 g
1 cup = 105 g 117 g
4 5
6 7

TABLE 5-3. Serving Lists for BCAA-Restricted Diets: Average Nutrient Content per Serving1
Food List Nutrient

ILE LEU VAL Protein Energy
Fats 7 10 7 0.1 70
Fruits 17 25 22 0.6 75
Vegetables 22 30 24 0.6 15
Alimentum ® Protein-Hydrolysate Formula With Iron, Ready to Feed, 100 mL 108 173 140 1.86 68
2
Isomil Soy Formula With Iron, Ready to Feed, 100 mL 2 74 135 76 1.66 68
Similac With Iron Infant Formula, Ready to Feed, 100 mL 2 75 144 83 1.40 68
Whole cow's milk, 100 mL 3 205 332 227 3.39 63
1
Reference 11.
2
3

TABLE 5.4. Equivalency Lists for BCAA-Restricted Diets: Gerber ® Baby Foods (Beikost) 1
Food Weight Approximate ILE LEU VAL Protein Energy

(g) Measure (mg) (mg) (mg) (g) (kcal)
BREADS AND CEREALS
Baked Finger Snacks

Animal crackers, cinnamon graham 8 1 cracker 17 34 20 0.5 35
Banana cookies 8 1 cookie 19 38 23 0.5 35
Strawberry fruit bars 9 1 bar 20 37 23 0.5 35
Veggie crackers 8 11 crackers 20 37 23 0.5 35
Cereals, Dry
Barley 4 1 Tbsp 18 35 24 0.5 15
Mixed 5 1 Tbsp + 1 tsp 16 38 21 0.5 19
Oatmeal 3 1 Tbsp 17 33 23 0.5 12
Oatmeal/banana 4 1 Tbsp 18 34 23 0.5 15
Oatmeal/mixed fruit 4 1 Tbsp 16 35 22 0.4 17
Rice 5 1 Tbsp + 1 tsp 18 34 24 0.4 19
Rice/apple bits 6 1 Tbsp + 2 tsp 16 33 21 0.4 25
Rice/apples 8 1 Tbsp + 2 tsp 16 35 23 0.5 31
Rice/banana 6 1 Tbsp + 2 tsp 15 33 21 0.4 23
Rice/mixed fruit 6 1 Tbsp + 2 tsp 16 35 23 0.4 24
Cereals, Jarred
1st Foods ®
Oatmeal 27 2 Tbsp 18 35 26 0.5 15
2nd Foods ®
Mixed/applesauce/bananas 55 3 Tbsp + 2-1/2 tsp 19 35 26 0.6 47
Oatmeal/applesauce/bananas 38 2 Tbsp + 2 tsp 18 35 24 0.5 32
Rice/applesauce 52 3 Tbsp + 2 tsp 17 35 23 0.4 47
3rd Foods ®
Mixed/apples/bananas 44 3 Tbsp 16 35 21 0.5 33
Oatmeal/apples/cinnamon 41 2 Tbsp + 2-1/3 tsp 16 35 22 0.5 27
Vegetables
1st Foods ®
Peas 16 1 Tbsp 21 36 26 0.5 8
Potatoes 67 1/4 cup + 2 tsp 21 35 34 0.7 31
Sweet potatoes 69 1/4 cup + 2-1/2 tsp 21 35 33 0.8 45
2nd Foods ®
Creamed corn 20 1 Tbsp + 1 tsp 14 35 18 0.4 13
Garden vegetables 24 1 Tbsp + 2 tsp 19 36 24 0.6 9
Mixed vegetables 41 2 Tbsp + 2-1/2 tsp 19 35 27 0.6 19
Peas 17 1 Tbsp + 1/2 tsp 21 36 26 0.5 8
Sweet potatoes 61 1/4 cup + 1 tsp 21 35 30 0.6 38
3rd Foods ®
Green beans/rice 42 3 Tbsp 18 35 23 0.5 18
Peas/rice 20 1 Tbsp + 1 tsp 20 35 24 0.4 10
Sweet potatoes 49 3 Tbsp + 1-1/4 tsp 23 35 32 0.7 39
FRUITS/JUICES
Mixed fruit juice 125 4 fl oz 13 24 18 0.3 70

Orange juice 188 6 fl oz 14 25 22 1.4 92
Pear juice 156 5 fl oz 13 24 16 0.5 76
1st Foods ®
Bananas 27 2 Tbsp 7 25 16 0.3 27
Peaches 100 7 Tbsp 14 25 19 0.7 43
Pears 132 1/2 cup + 1 Tbsp 13 25 17 0.5 75

Prunes 119 1/2 cup + 1 tsp 14 25 20 1.2 120
2nd Foods ®
Apricot/mixed fruit 100 7 Tbsp 13 26 19 0.6 60
Bananas 27 2 Tbsp 7 25 16 0.3 24
Bananas/apples/pears 36 2 Tbsp + 1-1/2 tsp 9 25 15 0.3 30
Hawaiian delight 25 1 Tbsp + 2-1/4 tsp 13 25 16 0.3 21
Peaches 100 7 Tbsp 14 25 19 0.7 64
Pears 125 1/2 cup + 2 tsp 15 25 20 0.6 92
Pear/pineapple 139 1/2 cup + 1-1/2 Tbsp 14 25 18 0.6 76
Plums/apple 156 1/2 cup + 3 Tbsp 14 25 19 0.6 109
Prunes/apple 119 1/2 cup + 1 tsp 13 25 15 0.7 92
3rd Foods ®
Apricots/mixed fruit 100 7 Tbsp 13 26 19 0.6 60
Bananas 27 2 Tbsp 7 25 16 0.3 24
Banana/pineapple 34 2 Tbsp + 1 tsp 8 25 15 0.3 26
Banana/strawberry 34 2 Tbsp + 1 tsp 8 25 16 0.3 32
Hawaiian delight dessert 25 1 Tbsp + 2-1/4 tsp 13 25 16 0.3 21
Peaches 125 1/2 cup + 2 tsp 15 25 20 0.9 80
Pears 125 1/2 cup + 2 tsp 15 25 20 0.6 92
Apple/sweet potato 179 5-3/4 fl oz 16 25 23 0.5 93
Graduates™, Fruit Dices
Peaches 192 ND 13 25 19 1.0 94
Pears 208 ND 12 25 19 0.6 112
Tender Harvest™
Apple/sweet potato 156 1/2 cup + 3 Tbsp 14 25 19 0.5 98
Banana/oatmeal/peach 28 2 Tbsp 10 25 16 0.3 21
Pears/winter squash 58 1/4 cup 15 25 19 0.6 30
Tropical fruit blend 58 1/4 cup 9 25 17 0.3 43
VEGETABLES
1st Foods ®
Carrots 91 6 Tbsp + 1 tsp 20 30 27 0.8 32
Green beans 30 2 Tbsp 15 30 20 0.4 9
Squash 55 4 Tbsp 23 30 21 0.4 19
2nd Foods ®
Carrots 91 6 Tbsp + 1 tsp 20 30 27 0.7 27
Green beans 37 2 Tbsp + 1-1/2 tsp 16 30 21 0.5 6
Squash 62 1/4 cup + 1 tsp 19 30 21 0.5 38
3rd Foods ®
Carrots 77 1/3 cup + 1 tsp 20 30 27 0.6 22
Squash 81 1/3 cup + 2 tsp 18 30 21 0.6 27
Graduates™, Vegetable Dices
Carrots 60 ND 17 30 23 0.4 14
Green beans 29 ND 17 30 21 0.3 7
Mixed vegetables 19 ND 13 30 16 0.4 9
Tender Harvest™
Butternut squash/corn 29 2 Tbsp 13 30 16 0.6 14
Garden carrots/brown rice 73 1/3 cup 17 30 24 0.7 34
Green beans/potatoes 16 1 Tbsp 16 30 20 0.4 10
Spring garden vegetables 41 2 Tbsp + 2-1/3 tsp 18 30 23 0.6 14
FREE FOODS A
Apple juice 94 3 fl oz 3 5 3 0.1 47

Apple/banana juice 39 1-1/4 fl oz 3 5 3 0.1 21
Apple/carrot juice 71 2-1/3 fl oz 4 5 6 0.1 30
Apple/cherry juice 62 2 fl oz 3 5 4 0.1 31
Apple/cranberry juice 62 2 fl oz 3 5 4 0.1 27
Apple/grape juice 125 4 fl oz 3 5 7 0.1 64
Apple/prune juice 62 2 fl oz 3 5 4 0.1 34
Fruit medley tropical dessert 55 3 Tbsp + 2-1/2 tsp 3 5 4 0.1 35
Guava tropical dessert 50 3 tbsp + 1-1/2 tsp 3 5 4 0.1 35
Mango tropical dessert 31 2 Tbsp + 1/2 tsp 3 5 4 0.1 23
Papaya tropical dessert 64 1/4 cup + 1-1/2 tsp 3 5 4 0.1 40
White grape juice 78 2-1/2 fl oz 3 5 4 0.2 54
1st Foods ®
Applesauce 43 3 Tbsp 3 5 4 0.1 23
2nd Foods ®
Apple/blueberry 45 3 Tbsp 3 5 4 0.1 22
Applesauce 29 2 Tbsp 3 5 3 0.1 14
Fruit medley dessert 43 3 Tbsp 3 5 4 0.2 35
Peach cobbler 31 2 Tbsp + 1/3 tsp 2 5 3 0.2 24
3rd Foods ®
Fruit salad 28 2 Tbsp 3 5 4 0.1 19
Peach cobbler 26 1 Tbsp + 2-1/2 tsp 2 5 3 0.2 23
Plums/apples 29 2 Tbsp 3 5 3 0.1 21
Graduates ® Beverages
Apple 93 3 fl oz 3 5 3 0.1 42
Apple banana 39 1-1/4 fl oz 3 5 3 0.1 20
Apple grape 124 4 fl oz 3 5 7 0.1 58
Berry punch 124 4 fl oz 3 5 7 0.1 63
Fruit punch 124 4 fl oz 3 5 7 0.1 60
Fruit Dices
Graduates™
Apples 71 ND 2 5 4 0.1 34
Mixed fruit 50 ND 3 5 4 0.1 25
Tender Harvest ®
Pear/wild blueberry 31 2 Tbsp + 1/2 tsp 2 5 3 0.1 9
1
ND = no data.
Weights and Measures: Except for Dry Cereals and Food Dices, the following weights apply:
Level Level
1 tsp = 1/3rd Tbsp = 4.8 g
1 Tbsp = 1/16th cup = 14.3 g
1/4 cup = 4 Tbsp = 57.2 g
1/3 cup = 5-1/3rd Tbsp = 76.2 g
1/2 cup = 8 Tbsp = 114.3 g
2/3 cup = 10 2/3rd Tbsp = 152.5 g
3/4 cup = 12 Tbsp = 171.5 g
1 cup = 16 Tbsp = 228.6 g

1
TABLE 5-4. Equivalency Lists for BCAA-Restricted Diets: Table Foods

BREADS AND CEREALS
Cereals, Cooked. Measure after cooking

Corn Grits, regular and quick 15 1 Tbsp 8 32 11 0.2 9
Cream of Rice ® 46 3 Tbsp 7 33 26 0.4 24
Cream of Wheat ®
instant 25 1 Tbsp + 2 tsp 20 35 22 0.4 16
quick 30 2 Tbsp 20 34 22 0.4 16
regular 31 2 Tbsp 21 36 23 0.5 17
Farina ® 29 2 Tbsp 18 32 20 0.4 14
Malt-o-Meal ® 15 1 Tbsp 17 29 22 0.4 9
Oats, regular, quick, and instant 15 1 Tbsp 17 29 22 0.4 9
Ralston ® 20 1 Tbsp + 1 tsp 20 34 22 0.4 11
Wheatena ® 23 1 Tbsp + 1-1/2 tsp 21 36 23 0.5 13
Whole Wheat Hot Natural 20 1 Tbsp 18 31 20 0.4 12

Alpha-Bits ® 5 3 Tbsp 18 35 23 0.4 21
Apple Jacks ® 5 1/4 cup 17 35 22 0.4 16
100% Bran ® 5 1 Tbsp + 1/2 tsp 19 37 28 0.6 13
Bran Chex ® 3 1 Tbsp 12 34 16 0.3 10
40% Bran Flakes (Post ®) 5 1 Tbsp + 1-1/2 tsp 21 35 28 0.6 16
Cap'n Crunch ® 5 2 Tbsp 10 30 13 0.2 20
Cap'n Crunch's ® Crunch Berries 5 2 Tbsp 10 29 12 0.2 18
Cap'n Crunch's ® Peanut Butter 5 2 Tbsp 13 32 16 0.3 19
Cheerios ® 3 2 Tbsp 20 33 25 0.4 11
Cinnamon Toast Crunch ® 17 1/4 cup + 3 Tbsp 18 36 21 0.6 70
Cocoa Krispies ® 8 1/4 cup 22 35 27 0.4 31
Cocoa Pebbles ® 9 1/4 cup 22 35 27 0.4 37
Cocoa Puffs ® 8 1/4 cup 10 35 14 0.3 31
Cookie Crisp ® 7 1/4 cup 14 35 18 0.4 28
Corn Bran ® 4 1 Tbsp + 1-1/2 tsp 13 38 16 0.3 16
Corn Chex ® 3 2 Tbsp 8 35 11 0.2 12
Corn Flakes ® 3 2 Tbsp 9 35 11 0.2 11
Crispy Rice ® 7 1/4 cup 8 36 28 0.4 28
Crispy Wheat'n Raisins ® 8 3 Tbsp 21 37 26 0.5 28
Froot Loops ® 6 3 Tbsp 14 35 17 0.3 21
Frosted Rice Krinkles 9 1/4 cup 22 35 28 0.4 35
Frosted Rice Krispies ® 9 1/4 cup 22 35 26 0.4 34
Fruity Pebbles™ 11 1/3 cup 23 35 28 0.4 43
Golden Grahams ® 5 2 Tbsp + 3/4 tsp 12 35 15 0.3 19
Grape Nuts Flakes ® 5 2 Tbsp + 1 tsp 21 36 26 0.5 18
Honeycomb ® 5 3 Tbsp + 1-1/4 tsp 11 35 14 0.3 18
Honey Nut Cheerios ® 3 1 Tbsp + 2/3 tsp 14 39 19 0.3 11
Honey Nut Corn Flakes ® 5 2 Tbsp 11 32 14 0.3 19
King Vitaman ® 5 1/4 cup 12 35 15 0.3 21
Kix ® 3 2 Tbsp + 1-1/2 tsp 11 34 14 0.3 12
Lucky Charms ® 5 3 Tbsp 21 35 27 0.5 19
Nutri-Grain ®
corn 3 1 Tbsp 8 36 11 0.2 10
rye 6 2 Tbsp + 1 tsp 22 34 27 0.5 21
wheat 5 2 Tbsp 20 35 23 0.5 20
Product 19 ® 3 1 Tbsp + 1-1/4 tsp 11 34 14 0.3 11
Quisp ® 6 3 Tbsp + 1-1/2 tsp 12 36 15 0.3 23
Raisin Bran (Post ®) 7 2 Tbsp 22 38 28 0.6 22
Rice Chex ® 8 1/3 cup 7 34 26 0.4 31

Rice Krispies ® 6 1/4 cup 22 35 30 0.5 24
Rice, puffed 7 1/2 cup 23 37 29 0.5 28
Special K ® 2 1 Tbsp + 1/2 tsp 20 32 23 0.4 8
Sugar Frosted Flakes ® 5 1 Tbsp + 3/4 tsp 9 35 11 0.2 17
Sugar Pops ® 5 2 Tbsp + 2 tsp 9 36 12 0.2 18
Sugar Smacks ® 7 3 Tbsp 21 36 24 0.5 26
Super Sugar Crisp ® 8 1/4 cup 23 38 26 0.5 31
Team ® 7 1/4 cup 20 36 25 0.4 26
Toasties ® 3 2 Tbsp 9 34 12 0.2 11
Total ® 4 2 Tbsp + 1/2 tsp 18 31 22 0.4 16
Trix ® 4 2 Tbsp + 1-1/2 tsp 10 33 13 0.2 17
Wheat Chex ® 5 1 Tbsp + 2 tsp 20 34 23 0.5 18
Wheat
puffed 3 1/4 cup 19 32 21 0.5 11
shredded 5 1/5 large biscuit 20 36 25 0.5 17
Wheaties ® 5 3 Tbsp 20 36 26 0.5 19
Grains
Corn, cooked
cream style 16 1 Tbsp 11 30 16 0.3 11
whole kernel 10 1 Tbsp 14 37 20 0.3 11
Rice, prepared
brown 18 1 Tbsp + 2 tsp 18 35 26 0.5 22
fried 14 1 Tbsp 17 29 22 0.4 18
Rice-A-Roni ® 16 1 Tbsp 17 32 21 0.5 20
white
long grain 16 1 Tbsp + 2 tsp 18 36 26 0.4 21
glutinous 21 1-1/2 Tbsp 18 35 25 0.4 20
medium grain 18 1-1/2 Tbsp 19 35 26 0.4 23
Pasta, cooked
Macaroni 10 1 Tbsp + 3/4 tsp 18 35 20 0.5 15
Noodles 13 1 Tbsp + 1/2 tsp 27 36 32 0.5 17
Ramen ® noodles 10 1 Tbsp 18 35 20 0.6 22
Spaghetti 9 1 Tbsp 16 31 18 0.5 14
Tubers
Potatoes, sweet
baked, in skin, mashed 25 1/4 small 25 37 33 0.5 30
candied or canned in syrup 49 1/4 cup 22 32 28 0.4 67
Potatoes, white
baked or boiled in skin 29 3 Tbsp 22 33 31 0.5 25
French fries (1/2" x 1/2" x 2") 15 3 fries 26 37 31 0.6 47
hash browns, frozen, cooked 20 2 Tbsp 27 37 31 0.6 43
Tater Tots ® 28 3 pieces 25 34 29 0.6 46
Yams, baked or boiled. mashed 34 1/4 cup 17 32 20 0.5 39
Miscellaneous
Chow mein noodles 5 1 Tbsp + 1-1/2 tsp 18 36 21 0.6 28
Jell-O ®, prepared w/ sugar 73 1/4 cup 16 35 29 1.1 43
Snack Foods
Arrowroot ® 5 1 biscuit 16 35 224 0.4 21
Barnum's Animal Crackers ® 8 3 crackers 18 35 21 0.5 33
Cookies
Oreo ® 11 1 cookie 17 32 21 0.5 53
Social Tea Biscuits ® 11 2 biscuits 21 39 24 0.6 48

Sugar Wafers (Nabisco ®) 14 2-1/2 wafers 18 34 20 0.6 67
vanilla wafer 8 2 wafers 15 30 17 0.4 37
Crackers
Goldfish ®, original 7 12 crackers 18 34 20 0.5 35
graham crackers (2" x 2") 7 1 cracker 20 38 23 0.6 27
Ritz ® 7 2 crackers 15 29 17 0.5 33
saltine 6 2 crackers 19 37 22 0.6 26
Triangle Thins ® 4 2 crackers 20 34 22 0.4 20
Waverly ® 7 1 cracker 17 33 20 0.5 35
Wheat Thins ® 7 4 crackers 17 34 20 0.5 34
Doritos ® 4 2 chips 8 31 12 0.3 18
Fritos ® 4 2 chips 10 34 13 0.3 22
Ice cream cone (wafer type) 4 1 (cone only) 15 30 18 0.4 17
Popcorn
buttered 2 1/4 cup 9 34 13 0.3 10
caramel 4 1 Tbsp + 2 tsp 9 34 12 0.2 14
plain 2 1/3 cup 9 36 12 0.2 7
Potato chips (2" diameter) 8 4 chips 21 31 29 0.5 42
Rice cakes 5 1/2 cake 21 33 26 0.4 17
FATS
Butter
stick 15 1 Tbsp 9 12 9 0.1 108
whipped 11 1 Tbsp + 1-1/2 tsp 6 9 6 0.1 79
Gravy
mushroom, canned 11 2-1/4 tsp 5 10 6 0.1 6
mushroom mix, dry 1 1 Tbsp 5 9 6 0.1 4
onion mix, dry 1 1 Tbsp 5 9 5 0.1 5
Margarine
soft in tub 14 1 Tbsp 6 9 6 0.1 101
stick or brick 14 1 Tbsp 6 12 9 0.1 101
Nondairy creamers w/ sodium caseinate
liquid 11 2-1/4 tsp 6 10 6 0.1 15
powder 2 1 tsp 6 9 7 0.1 11
Rich's ® Coffee Rich 43 3 Tbsp 6 10 6 0.1 66
Polyrich ® 43 3 Tbsp 6 10 6 0.1 66
Olives
black 15 3 olives 6 10 7 0.2 28
green 10 2 olives 4 8 6 0.2 12
French 18 1 Tbsp + 1 tsp 6 9 7 0.1 78
Italian 15 1 Tbsp 6 9 6 0.1 69
mayonnaise 9 2 tsp 6 9 7 0.1 66
Miracle Whip ® 28 2 Tbsp 7 10 7 0.1 140
ranch 5 1 tsp 6 9 7 0.1 26
Russian 8 1-1/2 tsp 7 10 8 0.1 38
Thousand Island 13 2-1/2 tsp 7 10 7 0.1 49
Cool Whip ®
extra creamy 4 2-1/2 tsp 6 10 7 0.1 13
regular 7 1 Tbsp + 2-1/4 tsp 6 10 7 0.1 19
Richwhip ®
pressurized 25 3 Tbsp + 1-1/4 tsp 6 10 6 0.1 69
prewhipped 10 2 Tbsp + 1-1/2 tsp 6 10 6 0.1 30

FRUITS
measuring or weighing.
Apple
canned, sweetened, sliced 204 1 cup 14 22 16 0.4 136
dried
cooked, sweetened 210 3/4 cup 16 26 19 0.4 174
uncooked 43 1/2 cup 16 25 19 0.4 104
sauce, canned, sweetened 255 1 cup 18 28 20 0.5 194
whole, large 230 1 fruit 18 28 21 0.4 136
Apricots
canned, heavy syrup 86 1/3 cup 14 27 16 0.5 71
dried
cooked, sweetened 31 2 Tbsp 12 23 14 0.4 38
uncooked 10 3 halves 12 22 14 0.4 25
frozen, sweetened 60 1/4 cup 12 24 15 0.4 60
nectar, canned 126 4 fl oz 14 26 16 0.5 72
whole 35 1 fruit 14 27 17 0.5 17
Avocados, all varieties, mashed 19 1 Tbsp + 1 tsp 13 23 18 0.4 31
Bananas 38 1/3 small 13 27 18 0.4 35
Blackberries
canned, heavy syrup 32 2 Tbsp 10 21 12 0.4 30
raw 72 1/2 cup 12 26 15 0.5 37
Blueberries
raw 72 1/2 cup 15 29 20 0.5 41
Boysenberries, canned, heavy syrup 48 3 Tbsp 14 21 18 0.5 42
Cherries
sour red, canned, heavy syrup 117 1/2 cup 16 23 21 0.9 106
sweet
canned, heavy syrup 97 6 Tbsp 17 26 22 0.6 80
raw 72 1/2 cup 17 24 22 0.9 52
Dates, dried 25 3 dates 12 22 16 0.5 68
Figs
dried
cooked 49 3 Tbsp 19 27 24 0.6 52
uncooked 19 1 fig 17 25 22 0.6 48
whole 75 1-1/2 medium 18 26 21 0.6 56
Fruit cocktail, canned, heavy syrup 130 1/2 cup 12 22 20 0.5 93
Fruit salad, canned, heavy syrup 128 1/2 cup 13 23 18 0.4 94
Gooseberries, canned, light syrup 63 1/4 cup 13 25 17 0.4 46
canned, light syrup 125 1/2 cup 23 21 37 0.9 46
juice, canned, unsweetened 185 6 fl oz 26 23 41 1.0 46
sections 115 1/2 cup 19 26 31 0.7 37
Grapes
adherent skin 160 1 cup 8 22 29 1.1 114
juice, canned or bottled 210 6 2/3 fl oz 15 25 21 1.2 129
slipskin 184 2 cups 10 24 32 1.2 484

Thompson, seedless, canned, heavy syrup 256 1 cup 10 26 33 1.2 186
Guava, common and strawberry
diced 41 1/4 cup 12 23 12 0.3 21
sauce 119 1/2 cup 15 25 13 0.4 44
Kiwi fruit 38 1/2 fruit 11 22 21 0.4 23
Loquats 100 10 fruits 15 26 21 0.4 47
Mangoes, diced 82 1/2 cup 15 26 22 0.4 54
Melon, cubed
cantaloupe 53 1/3 cup 14 21 18 0.5 19
casaba 57 1/3 cup 15 23 19 0.5 15
honeydew 113 2/3 cup 14 23 18 0.5 38
Mixed fruit, canned, heavy syrup 128 1/2 cup 14 24 21 0.5 92
Nectarines, sliced 69 1/2 cup 19 29 25 0.6 34
Oranges, all varieties
juice
canned 249 8 fl oz 15 27 22 1.5 104
frozen, diluted 187 3/4 cup 13 24 20 1.3 84
sections 90 1/2 cup 23 22 36 0.9 42
Orange-grapefruit juice, canned 187 6 fl oz 30 28 49 1.1 96
Papaya, diced 140 1 cup 14 22 11 0.9 54
Peaches
canned, heavy syrup, sliced 85 1/3 cup 11 22 21 0.4 63
dried, uncooked 13 1/2 fruit 14 26 26 0.5 31
nectar, canned 187 6 fl oz 15 29 27 0.5 100
sliced 57 1/3 cup 11 23 22 0.4 24
spiced, canned, heavy syrup 121 1/2 cup 15 28 28 0.5 90
Pears
canned, heavy syrup 255 1 cup 15 26 18 0.5 188
sliced 165 1 cup 33 23 23 0.6 97
Persimmons
Japanese 56 1/3 fruit 14 24 17 0.3 39
native 42 1-2/3 fruit 15 25 18 0.3 43
Pineapple
chunks
diced 155 1 cup 20 29 25 0.6 77
juice
canned 188 6 fl oz 20 26 25 0.6 104
frozen, diluted 156 5 fl oz 20 29 25 0.6 80
Plantains, cooked, sliced 77 1/2 cup 17 27 22 0.6 90
Plums
purple, canned, heavy syrup 258 1 cup 18 26 23 0.9 230
sliced 124 3/4 cup 20 25 23 1.0 68
Prunes
dried
cooked, unsweetened 71 1/3 cup 16 23 20 0.8 76
uncooked 34 4 fruits 17 24 22 0.9 80
juice, canned or bottled 160 5 fl oz 18 26 23 0.9 115
Raisins, seedless 41 1/4 cup 10 30 38 1.4 124
Raspberries
red, frozen, sweetened 83 1/3 cup 17 26 22 0.6 85
raw 62 1/2 cup 16 25 21 0.6 30
Rhubarb, frozen, cooked, sweetened 120 1/2 cup 14 21 18 0.5 139

Sapodilla, pulped 100 7 Tbsp 15 24 16 0.4 83
raw 75 1/2 cup 11 23 13 0.5 22
Tangerines
canned, light syrup 252 1 cup 30 28 48 1.1 153
juice
canned, sweetened 249 8 fl oz 121 25 20 1.2 125
fresh 247 8 fl oz 12 25 20 1.2 106
whole 168 2 medium 28 26 46 1.1 74
Watermelon, diced 160 1 cup 30 29 26 1.0 50
VEGETABLES
Asparagus green, raw, canned, cooked 33 2 Tbsp or 2 spears 18 32 26 0.7 9

Bamboo shoots, canned 37 1/3 cup 19 31 23 0.6 4
Beans, green, snap, or yellow wax
canned, cooked 26 3 Tbsp + 1 tsp 18 30 24 0.5 5
frozen, cooked 34 1/4 cup 17 28 23 0.5 9
Bean sprouts
mung
cooked 23 3 Tbsp 23 30 22 0.5 5
raw 17 2 Tbsp + 2 tsp 23 31 23 0.5 4
soya
cooked 14 1 Tbsp + 2 tsp 27 32 27 0.7 5
raw 12 2 Tbsp 27 32 27 0.7 6
Beets, canned, cooked
greens 27 3 Tbsp 14 31 21 0.7 8
roots, pickled, diced 74 7 Tbsp 24 33 27 0.8 23
Broccoli
fresh or frozen, cooked 20 2 Tbsp 22 27 27 0.6 6
raw, diced 22 4 Tbsp 24 29 28 0.6 6
Brussels sprouts
fresh, cooked 21 1 sprout 21 24 25 0.5 8
frozen, cooked 22 1 sprout 30 31 31 0.6 8
whole 19 1 sprout 25 29 29 0.6 8
Cabbage
Chinese
cooked 32 3 Tbsp 28 29 22 0.5 4
raw, shredded 35 1/2 cup 30 31 23 0.5 5
red, raw, shredded 39 1/3 cup 28 28 23 0.5 11
white, shredded
cooked 61 6 Tbsp 29 30 25 0.6 13
raw 52 2/3 cup 31 33 27 0.8 12
Carrots
fresh or frozen, cooked, 68 7 Tbsp 29 31 31 0.7 31
shredded 73 2/3 cup 30 31 32 0.7 31
Cauliflower
fresh or frozen, cooked 26 3 Tbsp + 1-1/4 tsp 19 30 25 0.5 6
diced 25 1/4 cup 19 29 25 0.5 6
Celery, diced
cooked 112 3/4 cup 18 27 23 0.6 17
raw 90 3/4 cup 18 28 23 0.6 14
Chard, Swiss, chopped
cooked 22 2 Tbsp 34 30 25 0.4 4

raw 25 3 Tbsp 26 32 23 0.6 6
Chayote fruit, cubed
cooked 53 1/3 cup 18 31 25 0.3 13
raw 33 1/4 cup 16 28 23 0.3 8
Collards, cooked, diced 47 1/4 cup 21 32 26 0.5 7
Cucumber, sliced 130 1-1/4 cup 22 30 22 0.7 17
Eggplant, cooked, diced 54 1/2 cup + 1 Tbsp 19 28 23 0.4 15
Endive, shredded 28 1/2 cup + 1 Tbsp 20 28 18 0.4 5
Kale, cooked, chopped 24 3 Tbsp 28 32 25 0.5 8
Kohlrabi, cooked 41 1/4 cup 34 29 22 0.7 12
Lettuce, shredded
bibb, Boston, or iceberg 42 3/4 cup 33 31 28 0.5 5
leaf 37 2/3 cup 31 29 26 0.5 7
Romaine or cos 28 1/2 cup 29 28 24 0.5 4
Mushrooms, Agaricus bisporus
cooked 20 2 Tbsp 17 27 20 0.4 5
raw, sliced 23 1/3 cup 19 30 23 0.5 6
Mustard greens, cooked, chopped 44 1/3 cup 36 30 39 1.0 7
Okra, cooked, sliced 30 3 Tbsp 21 29 26 0.6 10
Onions, mature
cooked, diced 105 1/2 cup 34 34 22 0.9 29
rings 10 1 ring 21 35 22 0.5 41
Parsnips, cooked, chopped 59 3/4 cup 32 28 25 0.8 47
Peas, green, fresh, or frozen, canned, cooked 10 1 Tbsp 19 32 23 0.5 8
Pepper, green, diced
cooked 85 3/4 cup 17 28 22 0.5 15
raw 66 2/3 cup 18 29 24 0.6 17
Pickle, cucumber
dill 100 1 large 22 30 24 0.7 11
sweet 100 1 large 22 30 22 0.7 146
Pumpkin, cooked 61 1/4 cup 21 31 23 0.7 21
Radishes, Oriental, cooked, sliced 74 1/2 cup 21 26 23 0.5 13
Rutabagas, cubed
cooked 85 1/2 cup 39 30 37 0.9 29
raw 70 1/2 cup 35 27 34 0.8 25
Sauerkraut, canned 58 1/4 cup 27 27 23 0.5 11
Shallots, chopped 20 2 Tbsp 21 30 22 0.5 14
Spinach, chopped
canned 13 1 Tbsp 19 29 21 0.4 3
fresh, cooked 11 1 Tbsp 17 26 19 0.3 3
frozen, cooked 12 1 Tbsp 18 29 21 0.4 8
raw 14 1/4 cup 20 31 22 0.4 3
Squash,
summer, all varieties, sliced
fresh, cooked 56 1/3 cup 19 30 23 0.5 11
frozen, cooked 50 1/4 cup 22 32 26 0.7 10
raw 43 1/3 cup 18 30 23 0.5 9
winter, all varieties
baked, boiled, or mashed 54 1/4 cup 19 27 21 0.5 21
Tomatoes
canned 84 1/3 cup 19 29 20 0.8 22
catsup 39 2 Tbsp + 1-1/2 tsp 23 31 23 0.8 41
cooked 75 1/3 cup 20 31 22 0.8 19
juice 137 41/2 fl oz 21 29 21 1.0 23
paste 29 1 Tbsp + 2-1/4 tsp 21 30 22 1.1 24
purée 62 1/4 cup 20 29 21 1.0 26

raw, diced 90 1/2 cup 19 30 21 0.8 17
sauce, no meat 81 1/3 cup 21 30 22 1.1 24
Turnips
greens, canned, chopped 27 3 Tbsp 16 28 21 0.3 5
root, diced
cooked 117 3/4 cup 34 30 27 0.8 21
raw 98 3/4 cup 35 32 29 0.9 26
Vegetable juice cocktail 182 6 fl oz 22 31 22 1.1 35
Soups, Campbell's ®, Condensed. Measure before diluting and dilute with water only.
Asparagus, Cream of 26 1 Tbsp + 2 tsp 20 34 24 0.5 18
Celery, Cream of 31 2 Tbsp 19 31 22 0.5 22
Chicken Gumbo 21 1 Tbsp + 1 tsp 17 28 20 0.4 9
Chicken Vegetable 15 1 Tbsp 17 29 20 0.4 9
Minestrone 15 1 Tbsp 16 30 22 0.5 10
Mushroom, Cream of 26 1 Tbsp + 2 tsp 20 33 22 0.4 27
Onion 31 2 Tbsp 33 33 22 0.9 14
Potato, Cream of 31 2 Tbsp 19 29 23 0.4 18
Tomato 42 2 Tbsp + 2 tsp 20 33 22 0.7 29
Tomato Bisque 31 2 Tbsp 19 32 21 0.5 30
Vegetarian Old-Fashioned 26 1 Tbsp + 2 tsp 21 31 21 0.5 14
Vegetarian Vegetable 25 1 Tbsp + 2 tsp 20 30 20 0.4 15
FREE FOODS A
Limit to prescribed number of servings.
Desserts
Apple butter 20 1 Tbsp 3 5 4 0.1 37
Fruit Ice 61 1/3 cup 6 6 10 0.2 78
Fruit bars, frozen
orange 56 3/4 bar 6 5 9 0.2 53
pineapple 24 1/3 bar 3 5 4 0.1 23
Gelatin Pop 15 1/3 pop 2 5 4 0.2 10
Marmalade 39 2 Tbsp 5 5 8 0.2 100
Marshmallow 8 1 large 2 5 4 0.2 26
M&M ® candy, plain 1 1 piece 3 5 3 0.1 4
Raisins, chocolate covered 1 1 raisin 3 6 4 0.1 6
Sorbet
peach 17 1 Tbsp + 1/2 tsp 2 5 5 0.1 17
pineapple 26 1 Tbsp + 2-1/4 tsp 3 5 4 0.1 25
strawberry 25 1 Tbsp + 2 tsp 2 5 3 0.1 24
Fruits/Juices
Apple juice, frozen, diluted 171 5-1/2 fl oz 3 5 3 0.1 80
Cranberry juice cocktail 253 8 fl oz 3 5 3 0.1 144
Fruit juice bar 104 2 bars 2 4 3 0.2 86
Fruit pie filling
apple 81 1/3 cup 3 5 4 0.1 89
cherry 81 2 Tbsp 3 4 4 0.2 33
peach 29 1 Tbsp + 2-1/4 tsp 29 3 5 0.1 31
strawberry 18 1 Tbsp + 1/2 tsp 2 5 3 0.1 20
Jams 20 1 Tbsp 3 6 3 0.1 54
Nectar
papaya 126 4 fl oz 3 5 4 0.2 71
pear 78 2-1/2 fl oz 2 5 3 0.1 47

Miscellaneous
Chocolate drink powder 3 1 tsp 3 5 3 0.1 11
Chocolate syrup 6 1 tsp 4 6 6 0.1 14
Honey 42 2 Tbsp 4 5 4 0.1 128
Vegetables
Chives, chopped 3 1 Tbsp 4 5 4 0.1 1
Cucumbers, sliced 26 1/4 cup 5 6 5 0.1 4
Horseradish 1 1-1/4 tsp 3 5 4 0.1 1
Leeks, chopped 6 1 Tbsp 4 6 4 0.1 4
Onions, spring, chopped 6 1 Tbsp 4 6 5 0.1 2
Peppers, jalapeño, canned, chopped 8 1 Tbsp 2 4 3 0.1 2
Radishes, sliced 14 2 Tbsp 4 5 5 0.1 3
FREE FOODS B
These foods contain little or no branched-chain amino acids. They may be used as desired if patient is not overweight and if they do not
depress appetite for prescribed foods.
Beverages
Carbonated beverages, caffeine-free 113 4 fl oz 0 0 0 0.0 52
Exceed ® Energy Drink 124 4 fl oz 0 0 0 0.0 35
Gatorade ® 125 4 fl oz 0 0 0 0.0 25
Kool-Aid ®, sweetened w/ sugar 125 4 fl oz 0 0 0 0.0 70
Lemonade 125 4 fl oz 1 1 1 0.0 49
Limeade, sweetened w/ sugar 125 4 fl oz 1 1 1 0.0 59
Strawberry drink powder 8 1 Tbsp 0 0 0 0.0 33
Tang ® 125 4 fl oz 0 0 0 0.0 59
Tea, instant, powder 1 1 Tbsp 0 0 0 0.0 3
Desserts/Sweeteners
Candies
candy corn 16 10 pieces 0 1 0 0.0 58
gum drops 16 8 pieces 0 1 0 0.0 56
hard candy 15 3 pieces 0 0 0 0.0 58
jelly beans 14 5 pieces 0 0 0 0.0 51
lollipop 28 1 medium 0 0 0 0.0 108
Frosting, strawberry or vanilla 16 1 Tbsp 0 0 0 0.0 69
Jellies 20 1 Tbsp 0 0 0 0.0 54
Lemon pudding, canned (Hunt's ®) 121 1 can 0 0 0 0.0 151
Molasses 21 1 Tbsp 0 0 0 0.0 48
Popsicle ®, twin 128 1 popsicle 0 0 0 0.0 95
Sugar
brown 14 1 Tbsp 0 0 0 0.0 52
powdered 8 1 Tbsp 0 0 0 0.0 31
table 12 1 Tbsp 0 0 0 0.0 48
Syrup
corn 20 1 Tbsp 0 0 0 0.0 58
maple 20 1 Tbsp 0 0 0 0.0 50
table 20 1 Tbsp 0 0 0 0.0 50
Miscellaneous
Salad dressing, oil/vinegar 16 1 Tbsp 0 0 0 0.0 70
1
See Appendix 12, p A-11, for composition of very-low-protein foods.

100 Maple Syrup Urine Disease
TABLE 5-5. MSUD Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

1 1 1
Length/ Weight Head Allo- ILE LEU VAL Hgb Hct FerritinTransthyretin Ketostix ® ILE LEU VAL Protein Energy
1
Height Circum isoleucine or DNPH
(mo/d/yr) (yrs/mos) (cm) (kg) (cm) (g/dL) (%) (ng/mL) (mg/dL) (mg) (mg) (mg) (g) (kcal)
1
Indicate if µmol/L or mg/dL.
REFERENCES
1985, 115-135.
2. Acosta PB, Yannicelli S: Nutrition support of inherited disorders of amino acids metabolism: Part 2. Top Clin Nutr
1995;10:48-72 (review).
Dis 2000;23 (Suppl) 1:29A.
1996.
6. Berry GT, Heidenreich R, Kaplan P, et al: Branched-chain amino acid free parenteral nutrition in the treatment of
acute metabolic decompensation in patients with maple syrup urine disease. N Engl J Med 1991;324:175-179.
8. Chuang DT, Shih VE: Maple syrup urine disease (Branched-chainketoaciduria). In Scriver CR, et al (eds): The
Metabolic and Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing Division,
2001, pp 1971-2005.
9. Clow CL, Reade TM, Scriver CR: Outcome of early and long-term management of classical maple syrup urine
disease. Pediatrics 1981;68:856-862.
10. DiGeorge AM, Rezvani I, Garibaldi LR, et al: Prospective study of maple syrup urine disease for the first four days
of life. N Engl J Med 1982;307:1492-1495.
12. Elsas LJ, Danner DJ: The role of thiamine in maple syrup urine disease. Ann NY Acad Sci 1982;378:404-421.
13. Elsas LJ, Ellerine NP, Klin PD: Practical methods to estimate whole body leucine oxidation in maple syrup urine
disease. Pediatr Res 1993;33:445-451.
14. Fernhoff PM, Lubitz D, Danner DJ, et al: Thiamine response in maple syrup urine disease. Pediatr Res
1985;19:1011-1016.
16. Giacoia GP, Berry GT: Acrodermatitis enteropathica-like syndrome secondary to isoleucine deficiency during
treatment of maple syrup urine disease. Am J Dis Child 1993;147;954-956.
concentrations and urea nitrogen in humans. JPEN 1991;15:48-53.
19. Gropper SS, Naglak MC, Nardella M, et al: Nutrient intakes of adolescents with PKU and infants and children with
MSUD on semisynthetic diets. J Am Col Nutr 1993;12:108-114.
20. Hammerson G, Wille L, Schmidt H, et al: Maple syrup urine disease: Treatment of the acutely ill newborn. Eur J
Pediatr 1978;129:157-165.
21. Henstenburg JD, Mazur AT, Kaplan PB, et al: Nutritional assessment and body composition in children with maple
syrup urine disease (MSUD). J Amer Diet Assoc 1990;90:A-32.
24. Kaplan P, Mazur A, Field M, et al: Intellectual outcome in children with maple syrup urine disease. J Pediatr
1991;119:46-50.
25. Kindt E, Halvorsen S: The need of essential amino acids in children: An evaluation based on the intake of
phenylalanine, tyrosine, leucine, isoleucine, and valine in children with phenylketonuria, tyrosine amino
transferase defect, and maple syrup urine disease. Am J Clin Nutr 1980;33:279-286.
26. Koch SE, Packman S, Koch TK, Williams ML: Dermatitis in treated maple syrup urine disease. J Am Acad
Dermatol 1993;28:289-292.
28. Lombeck I, Kasperek K, Harbisch HD, et al: The selenium state of children. II. Selenium content of serum, whole
blood, hair and the activity of erythrocyte glutathione peroxidase in dietetically treated patients with PKU and
MSUD. Eur J Pediatr 1978;128:213-223.

1982.
1987;1:1-17.
31. Naglak ME, Elsas LJ: Nutrition support of maple syrup urine disease. Metabolic Currents 1988;1:15-18.
32. Nord A, van Doorninck WJ, Greene C: Developmental profile of patients with maple syrup urine disease. J Inher
Metab Dis 1991;14:881-889.
33. Northrup H, Sigman ES, Herbert AA: Exfoliative erythroderma resulting from inadequate intake of branched-chain
amino acids in infants with MSUD. Arch Dermatol 1993;129:384-385.
35. Parsons HG, Carter RJ, Unrath M, Snyder FF: Evaluation of branched chain amino acid intake in children with
maple syrup urine disease and methylmalonic aciduria. J Inher Metab Dis 1990;13:125-136.
36. Peinemann F, Danner DJ: Maple syrup urine disease 1954 to 1993. J Inher Metab Dis 1994;17:3-15.
1955;56:231-251.
40. Schwahn B, Wendel U, Schadewaldt P, et al: Diurnal changes in plasma amino acids in maple syrup urine
disease. Acta Paediatr 1998;87:1245-1246.
Publisher, 1976.
1983;7:280-288.
44. Snyderman SE: Maple syrup urine disease. In Wapnir RA (ed): Congenital Metabolic Diseases: Diagnosis and
Treatment. New York: Marcel Dekker Inc, 1985.
45. Snyderman SE: The treatment of branched chain ketoacidemia. In Nutrition Committee: Diet Therapy for MSUD
and Organic Acidurias. Elk Grove Village, Ill: American Academy of Pediatrics, 1978.
46. Snyderman SE, Boyer A, Norton PM, et al: The essential amino acid requirements of infants: IX. Isoleucine. Am J
Clin Nutr 1964;15:313-321.
47. Snyderman SE, Holt LE, Smellie F, et al: The essential amino acid requirements of infants: Valine. Am J Dis Child
1959;97:186-191.
48. Snyderman SE, Roitman EL, Boyer A, et al: The essential amino acid requirements of infants: Leucine. Am J Dis
Child 1961;102:157-162.
1989;143:828-832.
50. Thompson GN, Francis DEM, Halliday D: Acute illness in maple syrup urine disease: Dynamics of protein
metabolism and implications for management. J Pediatr 1991;119:33-41.
51. Tornqvist K, Tornqvist H: Corneal deepithelialization caused by acute deficiency of isoleucine during treatment of a
patient with maple syrup urine disease. Acta Ophthalmol Scand 1996;74 (Suppl 219):48-49.
52. van Calcar S, Harding CO, Davidson SR, et al: Case reports of successful pregnancy in women with maple syrup
urine disease and propionic acidemia. Am J Med Genet 1992;44:641-646.
53. Wajner M, Schlottfeldt JL, Kless C, Wannmacher CMD: Immunosuppresive effects of organic acids accumulating
in patients with maple syrup urine disease. J Inher Metab Dis 1995;18:165-168.
54. Wendel U, Becker K, Przyrembel H, et al: Peritoneal dialysis in maple syrup urine disease: Studies on branched-
chain amino and ketoacids. Eur J Pediatr 1980;134:57-63.
55. Wendel U, Langenbeck U, Lombeck I, et al: Exchange transfusion in acute episodes of maple syrup urine disease.
Eur J Pediatr 1982;138:293.

PROTOCOL 6 — Disorders of Leucine Catabolism

I-VALEX ®-1 and I-VALEX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
Five mitochondrial enzyme defects have been identified in the catabolic pathway for essential leucine
(LEU) which normally produces acetoacetic acid and acetyl-CoA: branched-chain-α-ketoacid
dehydrogenase complex deficiency (Protocol 5); isovaleryl-CoA dehydrogenase deficiency;
3-methylcrotonyl-CoA carboxylase deficiency; 3-methylglutaconyl-CoA hydratase deficiency; and
3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMG-CoA lyase deficiency) (20, 68).
Isovaleric acidemia was first described in 1967 and was identified by urinary excretion of
isovaleric acid (IVA). Subsequently, a deficiency of isovaleryl-CoA dehydrogenase (IVD) was defined
in cultured skin fibroblasts. This enzyme is a mitochondrial flavoprotein and uses electron transfer
factor. Deficiency of IVD results in a block in catabolism of LEU at the step after branched-chain-α-
ketoacid dehydrogenase complex (Figure E) (20, 68).
IVA, 3-hydroxyisovaleric acid (3-OHIVA), and isovalerylglycine (IVG) accumulate in body fluids.
The phenotypic abnormalities result from toxic accumulation of free IVA. An alternate pathway
producing IVG reduces accumulation of toxic precursors. Carnityl adducts offer an additional alternate
pathway to detoxify free IVA (20, 23, 68).
Dietary protein Tissue protein
Isovaleric acid
L-Leucine Isovalerylglycine
Transaminase 3-Hydroxyisovaleric acid
4-Hydroxyisovaleric acid
Mesaconic acid
2-Keto-isocaproic acid Methylsuccinic acid
Branched-chain α-ketoacid Isovalerylglucuronide
dehydrogenase Isovalerylglutamic acid
Isovaleryl-CoA Isovalerylalanine
Isovalerylsarcosine
3-Hydroxyisoheptanoic acid
Isovalerylcarnitine
Isovaleryl-CoA dehydrogenase
3-Methylcrotonic acid
3-Methylcrotonyl-CoA 3-Methylcrotonylglycine
3-Hydroxyisovaleric acid
3-Methylcrotonyl-CoA carboxylase
3-Methylglutaconic acid
3-Methylglutaconyl-CoA 3-Methylglutaric acid
3-Methylglutarylcarnitine
3-Methylglutaconyl-CoA hydratase
3-Hydroxy-3-Methylglutaric acid
3-Hydroxy-3-methylglutaryl-CoA
3-Hydroxy-3-methylglutaryl-CoA
lyase 3-Hydroxy-3-methylglutaryl-CoA
reductase
Acetoacetic acid Acetyl-CoA Mevalonic acid Mevalonic acid

(Mevalonolactone)
Site of enzyme defect Cholesterol
¹ Modified from reference 68.
Figure E. Metabolism of leucine in disorders of leucine catabolism (excluding MSUD)

Two forms of isovaleric acidemia are reported: acute and chronic intermittent. Those patients with
acute isovaleric acidemia appear to be normal full-term infants. Within the 1st days of life, poor
feeding, tachypnea, vomiting, and a characteristic “sweaty-feet” odor of the blood and urine are
frequently noted. Diarrhea, lethargy, hypotonia, and tremors may also be found. Some patients fail to
respond to treatment and expire. The exact cause of death is frequently unknown. Severe metabolic
acidosis, hyperammonemia, central nervous system (CNS) hemorrhage, cardiac arrest, and sepsis
104 Disorders of Leucine Catabolism © 2001 Ross Products Division

are some probable causes. Infants who are detected early and respond to treatment survive the
neonatal period and develop appropriately. If acute neonatal disease is prevented, they progress into
chronic intermittent isovaleric acidemia (20, 68).
In the chronic intermittent form, babies are normal at birth. During late infancy, they may develop
episodes of vomiting, metabolic acidosis, stupor, and coma. “Sweaty-feet” odor is usually present, and
transient alopecia is occasionally seen. Episodes may begin as early as 2 weeks of age and the
frequency of attacks seems to decrease with age. Urinary tract and upper respiratory infections
frequently trigger episodes, as do excessive intake of protein and aspirin. Many children affected by
the intermittent form have a stronger preference for fruits and vegetables over meat and milk (20, 68).
Several patients with either acute or chronic isovaleric acidemia have had moderate to severe
hematologic abnormalities, including leukopenia and thrombocytopenia, with pancytopenia most
common. IVA is an inhibitor of granulopoietic progenitor cell proliferation in bone marrow cell cultures
and may account for the neutropenia often seen in isovaleric acidemia (39). Depressed hemoglobin
concentrations were also seen in several patients. Transient alopecia seems to be more common with
the chronic intermittent form than with the acute form of the disease and may be nutritionally related.
Hyperammonemia (up to 1200 µmol) has also been reported during neonatal crisis (72).

A male infant with isovaleric acidemia, treated from the neonatal period with medical food designed for
MSUD with added L-isoleucine and L-valine and whole protein to supply essential restricted LEU, had
normal growth and development. Height and weight were between the 25th and 50th percentiles. Head
circumference was at 50th percentile. On average, diet supplied 2.5-3.0 g protein/kg/day and 100 mg
LEU/kg/day (44). L-carnitine and glycine (GLY) were not a part of the diet regimen.
Growth of a male infant with isovaleric acidemia diagnosed prenatally has been reported (47). At
birth, this infant was breastfed ad libitum and 250 mg GLY/kg/day was administered. In spite of low
protein intake from human milk and the GLY supplement, the patient became acidotic and began to
vomit and hyperventilate at 3 days of age. Breastfeeding was discontinued and a LEU-free diet
providing 125 kcal/kg supplemented with 380 mg GLY/kg/day was begun. His clinical status improved
rapidly. Dietary LEU at 45 mg/kg/day with GLY at 250 mg/kg/day and protein at 2.0 g/kg was
introduced at 5 days of age. At 2 years of age, the patient was developmentally normal and was
> 95th percentile for height and weight. Diet at 2 years of age supplied per kg: 46 mg LEU, 1.7 g
protein and 72 kcal. Only one hospitalization for vomiting and dehydration was required during the
2-year period.
Outcomes in 9 patients with isovaleric acidemia managed by protein restriction (1.5-2.0 g/kg in
infancy, 0.8-1.5 g/kg thereafter) and 250 mg GLY/kg/day have been reported (12). Since all patients
had secondary carnitine deficiency (total serum carnitine 19 ± 3 µmol/L), 4 children were
supplemented with 50 mg/kg/day L-carnitine. In these patients serum carnitine returned to normal
(51 ± 5 µmol). Actual height, weight, and head circumference of patients were not reported although
growth velocities were stated to be normal after diet initiation. Developmental quotients or IQ scores
of 5 subjects in whom diet was initiated during the neonatal period ranged from 49 to 115.
Food refusal has been reported in a patient with isovaleric acidemia (35). Both physiologic and
behavioral components to feeding problems were reported. The physiologic component involved
altered serotonin metabolism. Any factor such as hyperammonemia or a high-carbohydrate, low-
protein diet that stimulates the transport of tryptophan, a precursor of serotonin, into the brain, could
lead to anorexia. A low-tryptophan diet was suggested as one alternative to treatment of anorexia.
Of 11 reported French cases of isovaleric acidemia, 8 were alive after the neonatal period. LEU
restriction and GLY supplementation were used to manage patients. Six of 8 surviving patients had
normal development (58).

A. Isovaleric Acidemia Resulting From Isovaleryl-CoA Dehydrogenase Deficiency
1. Diagnostic studies should be conducted in any infant or child with poor feeding, vomiting,
metabolic acidosis, hyperammonemia, hypocalcemia, coma, seizures, neutropenia,
thrombocytopenia, pancytopenia, ± alloisoleucine in plasma, ± tachypnea and/or sweaty-feet
or aged-cheese odor (4, 5, 13, 39, 54, 68).
2. See reference 68 for methods of diagnosis.
© 2001 Ross Products Division Disorders of Leucine Catabolism 105

B. 3-Methylcrotonylglycinuria Resulting From 3-Methylcrotonyl-CoA Carboxylase Deficiency
1. Diagnostic studies should be conducted in any infant or child who has hypotonia and lethargy
progressing to coma, or symptoms resembling Reye's syndrome (hypoglycemia,
hyperammonemia, metabolic acidosis, elevated transaminases, and seizures or
incoordination) (8, 9, 27, 42, 51, 57, 58).
2. See references 8 and 68 for methods of diagnosis.
C. 3-Methylglutaconic Aciduria Resulting From 3-Methylglutaconyl-CoA Hydratase Deficiency.
1. Diagnostic studies should be conducted in any infant or child who presents with mental
retardation, retarded speech, or fasting hypoglycemia with metabolic acidosis (15, 18, 25, 26
33, 34, 48).
2. See references 48 and 68 for methods of diagnosis.
D. 3-Hydroxy-3-Methylglutaric Aciduria Resulting From HMG-CoA Lyase Deficiency
1. Diagnostic studies should be conducted in any infant who has convulsions, coma, cyanosis,
dehydration, dyspnea, hyperpnea, hypotonia, lethargy, myoclonic jerks, opisthotonos, stroke-
like encephalopathy, respiratory distress, vomiting, hypoglycemia, metabolic acidosis, and
absent ketonuria, ± hyperammonemia, ± elevated transaminases, ± hepatomegaly (19, 22,
24, 28, 31, 34, 40, 43, 62, 67).
2. See reference 68 for methods of diagnosis.

1. Restrict dietary LEU to amount tolerated by patient to maintain treatment plasma LEU
concentration (12, 44).
2. For patients with HMG-CoA lyase deficiency, also restrict fat to between 20% and 25% of
energy and avoid fasting (6, 11).
B. Provide Alternative Metabolic Pathways
1. Prescribe adequate L-carnitine and GLY to decrease accumulated toxic compounds formed in
blocked reaction sequences (12, 14, 16, 17, 23, 37, 56).
V. Nutrition Support During Acute Illness

2. Evaluate plasma LEU concentrations and urine organic acid concentrations daily.
B. Medical Care
1. For medical management during diagnosis and acute illness, see references 4, 5, 16, 17, 23,
39, 41, 55, 74.
C. Patients Without Severe Neurologic Involvement
1. Begin high-energy LEU-free feeds (120-150 kcal/kg for infants and young children,
80-100 kcal/kg for children, and 40-50 kcal/kg for adults) that supply adequate water
(Table 6-1, p 115).
a. Depending on clinical status and age of patient, feed orally or by nipple, nasogastric tube,
intravenous infusion, or combine these methods.
1) For nipple or nasogastric feeds:
i. Use I-Valex (Table 6-2, p 116), L-carnitine (100-300 mg/kg), and GLY
(150-300 mg/kg (7) (Appendix 26, p A-28).
2) For intravenous feeds via central line:
i. Use hypertonic D-glucose, LEU-free parenteral amino acid solution (Appendix 26,
p A-28), L-carnitine (100-300 mg/kg) (14, 54, 69), and GLY (150-300 mg/kg)
(6, 16, 17, 36, 41, 46, 47, 59, 60, 70, 71).
ii. Add Liposyn ® II (Appendix 26, p A-28) after 2 to 3 days, when response to
glucose is seen. For 3-hydroxy-3 methylglutaric aciduria, Liposyn II should be
restricted to between 20% and 25% of energy (11, 24).

3) For intravenous feeds via peripheral line:
i. Use isotonic D-glucose, LEU-free parenteral amino acid solution, L-carnitine
(100-300 mg/kg) (55, 70) and GLY (150-300 mg/kg). Add Liposyn II (Appendix 26,
p A-28) when response to glucose is seen. For 3-hydroxy-3-methylglutaric
aciduria, Liposyn II should be restricted to between 20% and 25% of energy (11,
24).
2. Introduce nutrition support with I-Valex orally or by nasogastric tube as soon as possible.
a. See Table 6-1, p 115, for Recommended LEU, Protein, Energy, and Fluid intakes.
b. See Table 6-2, p 116 , for composition of I-Valex.
3. Add LEU (Table 6-1, p 115) to I-Valex feeds when plasma LEU concentration drops to upper
limit of treatment range (185 µmol/L).
a. Use Similac ® With Iron Infant Formula to fill LEU prescription for very young infants
(Table 6-3, p 117); Similac and beikost or table foods (Table 6-3, p 117) to fill prescription
for older infants; and whole cow’s milk (Table 6-3, p 117) or table foods to fill LEU
prescription for children and adults.
b. For patients with HMG-CoA lyase deficiency, use ProViMin ® Protein-Vitamin-Mineral
Formula Component With Iron to supply LEU (Table 6-4, p 118).
c. Measure liquid infant formula and whole cow’s milk with disposable syringe. Weigh
powdered infant formula on scale that reads in grams.
D. Comatose Patients
1. For medical management during diagnosis and acute illness, see references 16, 39, 41, 55,
68-74.
2. Begin LEU-free nasogastric feeding of protein and energy (I-Valex) (Tables 6-1 and 6-2,
pp 115 and 116) 36 to 48 hours after beginning dialysis with amino acid-free dialysate.
3. Begin intravenous infusion of 10% D-glucose, L-carnitine (100-300 mg/kg), and GLY
(150-300 mg/kg) during nasogastric feeding. Add L-carnitine and GLY only if amounts
provided by I-Valex are inadequate.
a. GLY is not beneficial in HMG-CoA lyase deficiency.
b. Add Liposyn II (Appendix 26, p A-28) to intravenous infusion in 2 to 3 days when response
to glucose is seen, continuing until major neurologic signs subside.
c. For HMG-CoA lyase deficiency, Liposyn II should provide between 20% and 25% of
energy.
4. Add LEU (Table 6-1, p 115) to I-Valex nasogastric feeding when plasma LEU concentration
drops to upper limit of range (185 µmol/L).
a. Use Similac to fill LEU prescription for infants (Table 6-3, p 117) and whole cow’s milk to
fill LEU prescription for children and adults.
b. For patients with HMG-CoA lyase deficiency, use ProViMin to supply LEU (Table 6-4,
p 118) for infants and skim milk for children and adults.
c. Measure liquid infant formula and whole or skim cow’s milk with disposable syringe.
VI. Establish Goals of Long-Term Nutrition Support (18)

A. Plasma LEU and GLY Concentrations
1. Maintain 2- to 4-hour postprandial plasma LEU concentrations between 50 and 100 µmol/L
(0.66 to 1.31 mg/dL) when measured by quantitative methods or between 2 and 4 mg/dL when
measured by bacterial inhibition assay.
2. Maintain 2- to 4-hour postprandial plasma GLY concentrations between 200 and 400 µmol/L
(1.5-3.0 mg/dL) when measured by quantitative methods.
1. Maintain normal osseous mineralization (41). Osteopenia may occur despite treatment.
in adults.

4. Prevent catabolism (46, 69).
b. Avoid extended periods of fasting in patients with HMG-CoA lyase deficiency (68).
5. Maintain normal blood hemoglobin, leukocyte, and platelet concentrations (39).
6. Maintain normal plasma anion gap.
7. Maintain plasma concentration of free carnitine > 30 µmol/L.
8. Maintain organic acid concentrations in urine in normal range (4).
a. Concentrations of organic acids in urine may be increased somewhat above normal even
when blood organic acids are in normal range.
9. Prevent alopecia.
C. Mental Development and Neurologic Status
1. Prevent developmental delay and mental retardation (12, 18).

A. LEU (1)
1. Prescribe LEU intake that promotes goals of nutrition support (Table 6-1, p 115).
2. LEU requirements vary widely:
a. From patient to patient, depending on activity of enzyme involved.
b. In same patient, depending on
1) Age.
2) Growth rate.
4) State of health.
5) GLY and L-carnitine intakes.
3. Values for LEU listed in Table 6-1, p 115, are suggested for initiating therapy.
4. Frequent monitoring of plasma LEU concentration and urinary excretion of organic acids is
essential to assess each patient’s changing requirements.
a. Compare results of plasma and urine monitoring with LEU intake.
b. See Section X, Suggested Evaluation of Nutrition Support, p 110.
Warning: Inadequate LEU intake will result in weight loss or poor weight gain, skin rash
progressing to desquamation, hair loss, below normal plasma LEU
concentration, loss of appetite, irritability, apathy, and increased
concentrations of plasma isoleucine, methionine, serine, threonine, and
valine (66).
B. GLY
1. Prescribe 150-300 mg/kg (47).
C. Protein (2)
1. Prescribe amount greater than Recommended Dietary Allowances (RDAs) (Table 6-1, p 115).
2. Requirements may be greater than RDAs when L-amino acids supply majority of protein
b. Early and high peak of plasma amino acids after ingestion of meals where large part of
protein is supplied by L-amino acids (29, 30).
Warning: Inadequate protein intake will result in weight loss or poor weight gain, skin
rash, hair loss, low plasma protein concentration, and decreased tolerance of
LEU.
D. Energy
appropriate weight for height of adults (Table 6-1, p 115).

3. At diagnosis and during metabolic acidosis precipitated by infection or trauma, energy needs
may be 25% to 40% greater than values listed in Table 6-1, p 115.
4. Maintenance of adequate energy intake is essential for normal growth and prevention of
catabolism (47, 69).
Warning: Inadequate energy intake results in poor weight gain or weight loss and
depressed tolerance of LEU.
E. L-Carnitine
1. Prescribe amount that will maintain plasma free carnitine concentration > 30 µmol/L. Most
patients require between 100 and 300 mg/kg (17, 23).
F. Fluid
1. Prescribe amount that will supply water requirements (Table 6-1, p 115).
2. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to
children and adults for each kcal ingested (10).
G. Fat
1. Restrict fat to between 20% and 25% of energy in patients with HMG-CoA lyase
deficiency (11, 24).
H. Pantothenic Acid
1. Supplements of 15 to 150 mg/day in three divided doses may be beneficial in
3-methylglutaconic aciduria (50).

A. LEU
1. Calculate amount of infant formula with iron, beikost, whole or skim milk, or table foods
required to fill LEU prescription (Table 6-3, p 117).
a. Low-iron infant formula, whole cow's milk, skim milk, and evaporated milk should not be
used as LEU source for infants because of low iron content.
b. Use ProViMin (Table 6-4, p 118) to supply LEU for infants with HMG-CoA lyase
deficiency.
2. Measure liquid infant formula or whole or skim milk with disposable syringe. Weigh powdered
3. Add beikost or table foods to gradually replace LEU provided by infant formula after infant is
4. Parents or patients may select any food in prescribed Servings Lists for BCAA-Restricted
Diets (Protocol 5, pp 88-99) in specified amounts to fill diet plan.
B. Protein
1. Calculate amount of protein provided by infant formula with iron, beikost, whole or skim milk,
or table foods (Table 6-3, p 117) required to fill LEU prescription.
a. Supplemental GLY is not included in protein calculation.
2. Subtract amount determined above from protein prescription.
3. Provide remaining prescribed protein with I-Valex (Table 6-2, p 116).
a. I-Valex is for infants and toddlers and I-Valex-2 is for children, adolescents, and adults.
b. Weigh I-Valex powder on scale that reads in grams because of variability of household
c. See Table 6-2 (p 116, footnote 3) for approximate packed weight of I-Valex powder in
C. GLY (Appendix 26, p A-28) (7)

1. Supply GLY as pure solution if amount present in I-Valex does not provide amount
prescribed.
a. Add GLY powder to boiled, cooled water to yield 100 mg/mL (eg, 100 g GLY with enough
water to yield 1 liter).
b. Refrigerate in sterilized, closed container until used. Discard unused suspension after
1 week, if not frozen.
c. Shake well before using. Measure GLY solution into medical food mixture with disposable
syringe.
D. Energy
1. Calculate energy provided by I-Valex (Table 6-2, p 116) and infant formula with iron, beikost,
whole or skim milk, or table foods (Table 6-3, p 117) required to fill LEU and protein
prescriptions.
2. Subtract amount of energy supplied by these sources from energy prescription.
Energy Module With Iron, Vitamins & Minerals (Appendix 11, p A-10), except for patients with
HMG-CoA lyase deficiency; sugar (48 kcal/Tbsp); or Free Foods B (Table 6-3, p 117).
a. Do not use corn syrup or table sugar for infants because of osmolarity they yield.
b. Do not use honey for infants because it may contain botulinum toxin.
4. Nasogastric or gastrostomy feeds may be required to maintain energy intake.
E. L-Carnitine (Appendix 26, p A-28)
1. If L-carnitine in I-Valex is inadequate to fill prescription, supply as pure solution.
2. Measure L-carnitine solution into medical food mixture with disposable syringe if entire
contents of container are not used.
3. L-carnitine tablets may be used if patient is old enough to swallow them (Appendix 26,
p A-28).
1. Add sufficient boiled, cooled water to infant formula, GLY solution (if needed), L-carnitine (if
needed), I-Valex, and energy source (if needed) to yield prescribed volume.
2. Mix with sterilized blender at lowest speed for 3 to 4 seconds. Excess mixing may
destabilize emulsion. Medical foods may also be mixed in sterilized, tightly closed container
by shaking vigorously for 10 to 12 seconds.
3. Place in sterilized formula bottles. Cap and store in refrigerator until used. Discard unused
portion 24 hours after mixing because of nutrient loss.
before feeding.
can burn infant and steam can make bottles explode.
8. For children and adults, chill I-Valex medical food mixture to improve taste.
G. Diet Guide
each diet change.
2. Feed infants 6 to 8 times daily (32, 61).
3. Feed children and adults 4 to 6 times daily (32, 61).

Prescription, p 107.
a. See Table 6-2, p 116, for composition of I-Valex and Table 6-3, p 117, for nutrient
composition of beikost or table foods, infant formula, and whole or skim milk.
a. See Appendices 4 through 7, pp A-4 to A-7, for composition of infant formulas.
not available.

c. If I-Valex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
foods and laboratory test results indicate need (Appendix 11, p A-10, for composition of
supplements).
B. Osmolarity
of I-Valex mixture is in acceptable range.
b. Osmolarity per gram of I-Valex is listed in Appendix 19, p A-21.
2. If osmolarity is > 450 mosm/L for infants, > 750 mosm/L for children, > 1,000 mosm/L for
C. Renal Solute Load
renal solute load.
a. This step is important to prevent dehydration of infants who may have renal-
concentrating capacity as low as 600 mosm/L.
recalculate.

A. Plasma LEU Concentration
1. Initial.
a. Evaluate every 2 to 3 days by quantitative methods until plasma concentrations stabilize
and approximate dietary LEU requirement is known.
2. Ongoing.
a. Evaluate weekly until patient is 1 year old if bacterial inhibition assay for LEU is available
in state laboratory.
b. Evaluate at least monthly by quantitative methods if weekly evaluations by bacterial
inhibition assay are conducted.
3. Unacceptable LEU concentrations.
a. If plasma LEU concentration is not detected and patient has ingested full prescription:
1) Increase prescribed LEU by 25% and reevaluate plasma LEU concentration in 3 days.
2) If LEU concentration remains undetected, repeat above process until value is in
treatment range.
b. If plasma LEU concentration is < 50 µmol/L or < 0.66 mg/dL and patient is ingesting full
prescription:
1) Increase prescribed LEU by 5% to 10%, then evaluate plasma LEU concentration in
1 week.
2) If plasma LEU concentration remains low, repeat above process until value is in
treatment range.
c. If plasma LEU concentration is > 100 µmol/L or > 1.31 mg/dL and patient is not ill and is
ingesting full prescription for LEU, protein, and energy:
1) Decrease prescribed LEU by 5% to 10% and reevaluate plasma LEU concentration in
1 week.
2) If plasma LEU concentration remains high, repeat above process until value is in
treatment range.
B. Urinary Organic Acid Excretion
1. Isovaleric acidemia.
a. Assess urinary IVA, 3-OHIVA, and IVG weekly to monthly when patient is well and every
1 to 3 days when patient is ill.

2. 3-Methylcrotonylglycinuria.
a. Assess urinary 3-OHIVA and 3-methylcrotonylglycine weekly to monthly when patient is
well and daily or every 2 to 3 days when patient is ill.
3. 3-Methylglutaconic aciduria.
a. Assess urinary 3-OHIVA, 3-methylglutaconic acid, and 3-methylglutaric acid weekly to
monthly when patient is well and daily or every 2 to 3 days when patient is ill.
4. 3-Hydroxy-3-methylglutaric aciduria.
a. Assess urinary 3-OHIVA, 3-methylglutaconic acid, 3-methylglutaric acid and 3-hydroxy-3-
methylglutaric acid weekly to monthly when patient is well and every 1 to 3 days when
patient is ill.
C. Urine Ketoacids by Ketostix ®
1. Evaluate daily for acetoacetic and ß-hydroxybutyric acids when patient is ill.
2. Results for urine ketoacids should be negative at all times.
3. If results for urine ketoacids are positive:
a. Immediately obtain blood sample for evaluation of LEU concentration by bacterial
inhibition assay or quantitative methods.
b. Brief metabolic physician on patient’s illness.
D. Protein Status
concentration in 1 month. If LEU concentration is in treatment range, use I-Valex to
increase protein.
E. Carnitine Status
1. Evaluate plasma free carnitine concentration weekly until amount of L-carnitine required to
maintain concentration > 30 µmol/L is determined, then evaluate every 3 months.
a. If free carnitine concentration in plasma is < 30 µmol/L:
1) Increase prescribed L-carnitine by 5-10%, then evaluate free carnitine concentration
in 1 week.
2) If free carnitine concentration remains low, repeat above process until value is in
treatment range.
F. Iron Status
standards).

G. Growth Status
a. Measure monthly to 1 year, every 3 months to 4 years, and every 6 months until full
growth is achieved. Plot measurements on NCHS growth charts.
a. Increase prescribed protein and energy by 5% to 10% and remeasure after 1 month.
achieved.
H. Bone Mineralization
1. Assess bone age and mineralization and look for signs of osteoporosis via yearly radiographs
of lumbar vertebrae.
I. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of LEU, GLY, carnitine, protein, and energy (plus fat in HMG-CoA lyase
deficiency).
3. Evaluate mineral and vitamin intake after each diet change.
not available.
J. Clinical Summary

A. Example 1
Establish and fill prescription for 3-month-old infant weighing 4.5 kg who has isovaleric acidemia,
using Recommended Daily Nutrient Intakes from Table 6-1, p 115, and nutrient contents from
LEU 80 mg/kg x 4.5 kg = 360 mg/day
GLY 150 mg/kg x 4.5 kg = 675 mg
L-Carnitine 150 mg/kg x 4.5 kg = 675 mg
Medical Food Mixture Measure LEU GLY L-Carnitine Protein Energy
I-Valex-1 81 g 0 810 729 12.2 389
1
Similac With Iron RTF 250 mL 360 70 3 3.5 170
Total per day 360 880 732 15.7 559

Total per kg 80 196 162 3.5 124
is 100 mosm.
1
RTF = Ready To Feed

B. Example 2
Nutrient Intakes from Table 6-1, p 115, and nutrient contents from Tables 6-2 and 6-3, pp 116
and 117.
LEU 500 mg/day
GLY 1,300 mg
L-Carnitine 1,300 mg
Protein 30 g
Energy 1,300 kcal
Fluid 1,300 mL
Medical Food Mixture Measure LEU GLY L-Carnitine Protein Energy
I-Valex-1 140 g 0 1,400 1,260 21.0 672
Food List Servings

Breads/Cereals 5 175 0 0 2.5 150
Fats 1 10 0 0 0.1 70
Fruits 4 100 0 0 2.4 300
Vegetables 7 210 0 0 4.2 105
Total per day 495 1,400 1,260 30.2 1,297
C. Example 3
Establish and fill prescription for 3-year-old child weighing 17 kg who has
3-methylcrotonylglycinuria. Use the Recommended Daily Nutrient Intakes from Table 6-1, p 115,
and nutrient contents from Tables 6-2 and 6-3, pp 116 and 117.
LEU 600 mg/day
GLY 1,700 mg
L-Carnitine 1,275 mg
Protein 30 g
Energy 1,300 kcal
Fluid 1,300 mL
Medical Food Mixture Amount LEU GLY L-Carnitine Protein Energy
I-Valex-2 67 g 0 2,023 1,206 20.1 275
Food List Servings

Breads/Cereals 8 280 0 0 4.0 240
Fats 4 40 0 0 0.4 280
Fruits 6 150 0 0 3.6 450
Vegetables 4 120 0 0 2.4 60
Total per day 590 2,023 1,206 30.5 1,305

D. Example 4
Establish and fill prescription for 6-month-old child weighing 7 kg who has 3-hydroxy-3-
methylglutaric aciduria. Use Recommended Daily Nutrient Intakes from Table 6-1, p 115, average
nutrient contents from Tables 6-2 through 6-4, pp 116-118.
LEU 490 mg/day
L-Carnitine 700 mg
Protein 19.2 g
Energy 805 kcal
Fat 18 g
Fluid 910 mL
Medical Food Mixture Measure LEU L-Carnitine Fat Protein Energy
(mg) (mg) (g) (g) (kcal)
I-Valex-1 81 g 0 729 17.6 12.2 389
ProViMin 2.9 g 196 1 0.0 2.1 9
Sugar 8 g (2 tsp) 0 0 0.0 0.0 32
Add water to make 710 mL (24 fl oz). Offer additional water ad libitum daily.
Food List Servings

Breads/Cereals 3 105 0 0.0 1.5 90
Fruits 3 75 0 0.0 1.8 225
Vegetables 4 120 0 0.0 2.4 60
Total per day 496 730 17.6 20.0 805

A. Rationale
2. Well-nourished patients with disorders of leucine catabolism respond to infection and trauma
as do normal persons.
3. Febrile illness and trauma are life-threatening if not diagnosed and treated promptly.
4. See Section V, Nutrition Support During Acute Illness, p 105.
XIII. Contraindicated Medications

A. Benzoic acid (sodium benzoate) (55).
1. However, benzoic acid may be used for short periods if patient is hyperammonemic.
B. Salicylates (41, 55).

TABLE 6-1. Recommended Daily Nutrient Intakes (Average and Range) for Infants, Children and Adults
With Disorders of LEU Catabolism
Age Nutrient
1,2 3,4
LEU Protein Energy 3 Fluid 5
Infants
0 to < 3 mo 80 - 150 3.50 - 3.00 120 (145 - 95) 160-125
3 to < 6 mo 70 - 140 3.50 - 3.00 115 (145 - 95) 160-130
6 to < 9 mo 60 - 130 3.00 - 2.50 110 (135 - 80) 145-125
9 to < 12 mo 50 - 120 3.00 - 2.50 105 (135 - 80) 135-120
(mg/day) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 500 - 900 > 30.0 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 600 - 900 > 35.0 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 700 - 900 > 40.0 2,400 (1650 - 3300) 1,730 - 3,300
Women
11 to < 15 yr 700 - 900 > 50.0 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 620 - 820 > 55.0 2,100 (1200 - 3000) 1,200 - 3,000
> 19 yr 620 - 820 > 60.0 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 1,100 - 1500 > 55.0 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 1,100 - 1500 > 65.0 2,800 (2100 - 3900) 2,100 - 3,900
> 19 yr 1,000 - 1400 > 70.0 2,900 (2000 - 3300) 2,000 - 3,300
1
Modified from references 1 and 66. Initiate therapy with lowest value for age. Modify prescription based on
frequently obtained blood and/or plasma values and growth in infants and children and frequently obtained
plasma values and weight maintenance in adults.
2
3
During metabolic acidosis and/or infection following trauma, energy requirements may be 25-40% greater than those
listed. Initiate therapy with energy value outside parentheses.
4
Modified from reference 10. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL
fluid to children and adults for each kcal ingested.

TABLE 6-2. Nutrient Composition of I-VALEX ®-1 1, 3, and I-VALEX ®-2 2, 3
Nutrient I-Valex-1 I-Valex-2

Energy, kcal 480 32 410 13.7
Protein Equiv, g 15.00 1.000 30.00 1.000
Nitrogen, g 2.40 0.160 4.80 0.160
Amino Acids, g 16.01 1.067 32.02 1.067
Cystine, g 0.15 0.010 0.30 0.010
Glycine, g 1.00 0.067 3.02 0.101
Histidine, g 0.42 0.028 0.84 0.028
Isoleucine, g 0.43 0.029 0.86 0.029
Leucine, g trace 0.000 trace 0.000
Lysine, g 1.00 0.067 2.00 0.067
Methionine, g 0.30 0.020 0.60 0.020
Phenylalanine, g 0.88 0.059 1.76 0.059
Threonine, g 0.70 0.047 1.40 0.047
Tryptophan, g 0.17 0.011 0.34 0.011
Tyrosine, g 0.89 0.059 1.78 0.059
Valine, g 0.48 0.032 0.96 0.032
Carnitine, mg 900 60 1,800 60
Taurine, mg 40 2.67 50 1.67
Carbohydrate, g 53.0 3.53 35 1.17
Fat, g 21.7 1.45 13 0.43
4 5
Linoleic acid, g 2.00 0.133 1.50 0.050
6 7
0.36 0.024 0.17 0.006
Minerals
Calcium, mg 575 38 880 29
Chloride, mg/mEq 325/9.17 21.7/0.61 940/26.51 31.33/0.88
Chromium, µg 11 0.73 27 0.90
Copper, mg 1.10 0.073 1.00 0.033
Iodine, µg 65 4.33 100 3.33
Iron, mg 9.0 0.60 13 0.43
Magnesium, mg 50 3.33 225 7.50
Manganese, mg 0.50 0.033 0.80 0.027
Potassium, mg/mEq 675/17.26 45/1.15 1,370/35.04 45.7/1.17
Selenium, µg 20 1.33 35 1.17
Sodium, mg/mEq 190/8.26 12.7/0.55 880/38.28 29.3/1.28
Zinc, mg 8.0 0.53 13.0 0.43
Vitamins
A, µg RE 420 28 660 22
D, µg 7.50 0.50 7.50 0.25
E, mg α-TE 10.10 0.67 12.10 0.40
K, µg 50 3.33 60 2.00
Biotin, µg 65 4.33 100 3.33
B6, mg 0.75 0.050 1.30 0.043
B12, µg 4.90 0.327 5.00 0.167
Choline, mg 80 5.33 100 3.33
Folate, µg 230 15 430 14.33
Inositol, mg 40 2.67 70 2.33
Niacin equiv, mg 12.80 0.850 21.7 0.72
Riboflavin, mg 0.90 0.060 1.80 0.060
Thiamin, mg 1.90 0.127 3.25 0.108
1 2
3
Approximate packed weights of I-Valex in level, dry US standard household measures:
I-Valex-1 I-Valex-2
1 Tbsp = 7g 8g
1/4 cup = 26 g 32 g
1/3 cup = 35 g 41 g
1/2 cup = 53 g 61 g
1 cup = 105 g 117 g
4 5
6 7

TABLE 6-3. Serving Lists for LEU-Restricted Diets: Approximate LEU, Protein, Fat, and Energy Content per
Serving1
Food List Nutrient

LEU Fat Protein Energy
(mg) (g) (g) (kcal)
Breads/Cereals 35 0.00 0.50 30
Fats 10 8.00 0.10 70
Fruits 25 0.00 0.60 75
Vegetables 30 0.00 0.60 15
Free Foods A 5 varies 0.10 50
Free Foods B 0 varies 0 00 55
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 2 173 3.74 1.86 68
Isomil ® Soy Formula With Iron, Ready to Feed, 100 mL 2 135 3.70 1.66 68
Similac ® With Iron Infant Formula, Ready to Feed, 100 mL 2 144 3.65 1.40 68
Skim milk, 100 mL 3 346 0.19 3.53 36
3
Whole cow’s milk, 100 mL 332 3.46 3.39 63
1
From reference 20.
2
3

TABLE 6-4. Nutrient Composition of ProViMin ® and Skim Milk
1 2
Nutrient ProViMin Skim Milk
(per 100 g powder) (per 100 mL)
Energy, kcal 312 36
Protein Equiv, g 73.0 3.53
Amino Acids, g 79.59 3.58
Cystine, mg 410 33
Glycine, mg 1,380 75
Histidine, mg 1,950 95
Isoleucine, mg 3,400 213
Leucine, mg 6,750 346
Lysine, mg 5,760 280
Methionine, mg 2,200 89
Phenylalanine, mg 3,630 171
Threonine, mg 3,130 159
Tryptophan, mg 1,000 50
Tyrosine, mg 4,150 171
Valine, mg 4,250 236
Carnitine, mg 40 NA
Taurine, mg 110 NA
Carbohydrate, g 2.00 5.02
Fat, g 1.4 0.19
Linoleic acid, g 0 0.005
α-Linolenic acid, g 0 0.002
Minerals
Calcium, mg 2,400 127
Chloride, mg/mEq 2,300/65 104/2.93
Copper, mg 2.10 0.01
Iodine, µg 335 7
Iron, mg 40 0.04
Magnesium, mg 200 11
Phosphorus, mg 1,700 105
Potassium, mg/mEq 3,300/84 172/4.4
Selenium, µg 70 2.17
Sodium, mg/mEq 1,200/52 54/2.35
Zinc, mg 17 0.41
Vitamins
A, µg RE 2,020 63
D, µg 25 1.06
E, mg α-TE 45 0.04
K, µg 90 NA
Ascorbic acid, mg 200 1.01
Biotin, µg 100 2.00
B6, mg 1.35 0.04
B12, µg 5.6 0.39
Choline, mg 335 NA
Folate, µg 320 5.18
Inositol, mg 105 NA
Niacin equiv, mg 40.6 0.92
Thiamin, mg 2.24 0.04
1
Approximate weight in grams of level, dry, US standard household measures:
1 Tbsp = 2.9 g
1/4 cup = 11 g
2/3 cup = 30 g
1 cup = 44 g
2
From reference 52.
NA = Not available.

TABLE 6-5. Isovaleric Acidemia Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

1
Length/ Weight Head Free GLY IVA LEU Hgb Hct Ferritin Trans- Urine LEU GLY Carnitine Protein Energy
1 2 3
Height Circum Carnitine thyretin IVA OHIVA IVG
(mo/d/yr)
(yrs/mos) (cm) (kg) (cm) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (g/dL) (%) (ng/mL) (mg/dL) (mg) (mg) (mg) (g) (kcal)
Disorders of Leucine Catabolism 119
1
Isovaleric acid.
2
ß-hydroxyisovaleric acid.
3
Isovalerylglycine
REFERENCES
1985, 115-135.
Dis 2000;23 (Suppl 1):29A.
4. Arnold WC, Brewster M, Byrne WJ, Booth B: Fanconi syndrome in a patient with a variant of isovaleric acidemia.
Int J Pediatr Nephrol 1986;7:95-98.
5. Attia N, Sakati NAL, Ashwal A, et al: Isovaleric acidemia appearing as diabetic ketoacidosis. J Inher Metab Dis
1996;19:85-87
6. Bakker HD, Wanders RJA, Schutgens RBH, et al: 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency: Absence of
clinical symptoms due to a self-imposed dietary fat and protein restriction. J Inher Metab Dis 1993;16:1061-1062.
7. Bartlett K, Gompertz D: The specificity of glycine-N-acylase and acylglycine excretion in the organic acidaemias.
Biochem Med 1974;10:15-23.
8. Baumgartner R: Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency. In Fernandes J, et al (eds):
Inborn Metabolic Diseases: Diagnosis and Treatment. New York: Springer-Verlag, 1990, pp 321-322.
9. Beemer FA, Bartlett K, Duran M, et al: Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency in two
sibs. Eur J Pediatr 1982;138:351-354.
1996.
11. Berry HK, Suchy F, Hunt M, Norman E: Treatment of 3-hydroxy-3-methylglutaric aciduria in first cousins. In
Walser M, et al (eds): Metabolism and Clinical Implications of Branched Chain Amino and Ketoacids. New York:
Elsevier, 1981, pp 395-400.
12. Berry GT, Yudkoff M, Segal S: Isovaleric acidemia: Medical and neurodevelopmental effects of long-term therapy.
J Pediatr 1988;113:58-64.
13. Budd MA, Tanaka K, Holmes LB, et al: Isovaleric acidemia. Clinical features of a new genetic defect of leucine
metabolism. N Engl J Med 1967;277:321-327.
14. Chalmers RA, Stacey TE, Tracey BM, de Sousa C: L-carnitine insufficiency in disorders of organic acid
metabolism: Response to L-carnitine by patients with methylmalonic aciduria and 3-hydroxy-3-methylglutaric
aciduria. J Inher Metab Dis 1984;7 (Suppl 2):109-110.
15. Chitayat D, Chemke J, Gibson KM, et al: 3-Methylglutaconic aciduria: A marker for as yet unspecified disorders
and the relevance of prenatal diagnosis in a “new” type (type 4). J Inher Metab Dis 1992;15:204-212.
16. Cohn RM, Yudkoff M, Rothman R, Segal S: Isovaleric acidemia: Use of glycine therapy in neonates. N Engl J Med
1978;299:996-999.
17. de Sousa C, Chalmers RA, Stacey TE, et al: The response to L-carnitine and glycine therapy in isovaleric
acidemia. Eur J Pediatr 1986;144:451-456.
18. Duran M, Beemer FA, Tibosch AS, et al: Inherited 3-methylglutaconic aciduria in two brothers — another defect of
leucine metabolism. J Pediatr 1982;101:551-554.
19. Duran M, Schutgens RBH, Ketel A, et al: 3-Hydrox-3-methylglutaryl coenzyme A lyase deficiency: Postnatal
management following prenatal diagnosis by analysis of maternal urine. J Pediatr 1979;95:1004-1007.
22. Francois B, Bachmann C, Schutgens RBH: Glucose metabolism in a child with 3-hydroxy-3-methyl-glutaryl-
coenzyme A lyase deficiency. J Inher Metab Dis 1981;4:163-164.
23. Fries MH, Rinaldo P, Schmidt-Sommerfeld E, et al: Isovaleric acidemia: Response to a leucine load after three
weeks of supplementation with glycine, L-carnitine, and combined glycine-carnitine therapy. J Pediatr
1996;129:449-452.
24. Gibson KM, Breuer J, Nyhan WL: 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: Review of 18 reported
patients. Eur J Pediatr 1988;148:180-186.
25. Gibson KM, Lee CF, Wappner RS: 3-Methylglutaconyl-coenzyme-A hydratase deficiency: A new case. J Inher
Metab Dis 1992;15:363-366.
26. Gibson KM, Sherwood WG, Hoffmann GF, et al: Phenotypic heterogeneity in syndromes of 3-methylglutaconic
aciduria. J Pediatr 1991;118:885-890.
27. Gitzelmann R, Steinmann B, Niederwieser A, et al: Isolated (biotin-resistant) 3-methylcrotonyl-CoA carboxylase
deficiency presenting at age 20 months with sopor, hypoglycaemia, and ketoacidosis. J Inher Metab Dis
1987;10 (Suppl 2):290-292.
28. Greene CL, Cann HM, Robinson BH, et al: 3-Hydroxy-3-methylglutaric aciduria. J Neurogenet 1984;1:165-173.
31. Gunel M, Coskum T, Tokathi A, Ozalp I: 3-Hydroxy-3-methylglutaryl coenzyme A lyase deficiency. J Inher Metab
Dis 1993;16:1062-1063.
mixture on different amounts of single dose ingested: A case report. Eur J Pediatr 1994;153:501-503.
33. Hou JW, Wong TR: 3-Methylglutaconic aciduria presenting as Reye syndrome in a Chinese boy. J Inher Metab Dis
1995;18:645-646.
34. Huemer M, Muehl A, Wandl-Vergesslich K, et al: Stroke-like encephalopathy in an infant with 3-hydroxy-3-
methylglutaryl-coenzyme A lyase deficiency. Eur J Pediatr 1998;157:743-746.
35. Hyman SL, Porter CA, Page TJ, et al: Behavior management of feeding disturbances in urea cycle and organic
acid disorders J Pediatr 1987;111:558-562.
36. Ito T, Kidouchi K, Sugiyama N, et al: Liquid chromatographic-atmospheric pressure chemical ionization mass
spectrometric analysis of glycine conjugates and urinary isovalerylglycine in isovaleric acidemia. J Chromat
1995;B670:317-322.
37. Itoh T, Ito T, Ohba S, et al: Effect of carnitine administration on glycine metabolism in patients with isovaleric
acidemia: Significance of acetylcarnitine determination to estimate the proper carnitine dose. Tohoku J Exp Med
1996;179:101-109.
39. Kelleher JF, Yudkoff M, Hutchinson R, et al: The pancytopenia of isovaleric acidemia. Pediatrics
1980;65:1023-1027.
40. Ketel A, Ket JL, Schutgens RBH, et al: Clinical and biochemical observations on a child with a deficiency of
3-hydroxy-3-methylglutaryl coenzyme A lyase. J Inher Metab Dis 1980;3:89-90.
41. Krieger I, Tanaka K: Therapeutic effects of glycine in isovaleric acidemia. Pediatr Res 1976;10:25-29.
42. Lehnert W, Niederhoff H, Suormala T, Baumgartner ER: Isolated biotin-resistant 3-methylcrotonyl-CoA
carboxylase deficiency: Long-term outcome in a case with neonatal onset. Eur J Pediatr 1996;155:568-572.
43. Leupold D, Bojasch M, Jakobs C: 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency in an infant with macrocephaly
and mild metabolic acidosis. Eur J Pediatr 1982;183:73-76.
44. Lott IT, Erickson AM, Levy HL: Dietary treatment of an infant with isovaleric acidemia. Pediatrics 1972;49:616-618.
1982.
46. Millington DS, Roe CR, Maltby DA, Inoue F: Endogenous catabolism is the major source of toxic metabolites in
isovaleric acidemia. J Pediatr 1987;110:56-60.
47. Naglak M, Salvo R, Madsen K, et al: The treatment of isovaleric acidemia with glycine supplements. Pediatr Res
1988;24:9-13.
48. Narisawa K, Gibson KM, Sweetman L, et al: Deficiency of 3-methylglutaconyl- coenzyme A hydratase in two
siblings with 3-methylglutaconic aciduria. J Clin Invest 1986;77:1148-1152.
50. Ostmann-Smith I, Brown G, Johnson A, Land JM: Dilated cardiomyopathy due to type II X-linked
3-methylglutaconic aciduria: successful treatment with pantothenic acid. Br Heart J 1994;72:349-53.
51. Pearson MA, Aleck KA, Heidenreich RA: Benign clinical presentation of 3-methylcrotonylglycinuria. J Inher Metab
Dis 1995;18:640-641.
1955;56:231-251.
54. Riubier D, Parvy P, Bardet J, et al: Alloisoleucine in isovaleric acidemia. J Inher Metab Dis 1992;15:154-155.
55. Roe CR, Millington DS, Maltby DA: Identification of 3-methylglutaryl-carnitine. J Clin Invest 1984;77:1391-1394.
56. Roe CR, Millington DS, Maltby DA, et al: L-carnitine therapy in isovaleric acidemia. J Clin Invest
1984;74:2290-2295.
57. Rolland MD, Divry P, Zabot MT, et al: Isolated 3-methylcrotonyl-CoA carboxylase deficiency in a 16-month-old
child. J Inher Metab Dis 1991;14:838-839.
58. Rousson R, Guidbaud P: Long term outcome of organic acidurias: Survey of 105 French cases (1967-1983).
J Inher Metab Dis 1984;7 (Suppl 1):10-12.
59. Rutledge SL, Berry GT, Stanley CA, et al: Glycine and L-carnitine therapy in 3-methylcrotonyl-CoA carboxylase
deficiency. J Inher Metab Dis 1995;18:229-305.
60. Salamino F, DiLisa F, Burlina AB, et al: Involvement of erythrocyte calpain in glycine- and carnitine-treated
isovaleric acidemia. Pediatr Res 1994;36:182-186.

62. Shilkin R, Wilson G, Owles E: 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. Acta Paediatr Scand
1981;70:265-268.
Publisher, 1976.
1983;7:280-288.
Child 1961;102:157-162.
67. Stacey TE, de Sousa C, Tracey BM, et al: Dizygotic twins with 3-hydroxy- 3-methylglutaric aciduria: Unusual
presentation, family studies, and dietary management. Eur J Pediatr 1985;1444:177-181.
68. Sweetman L, Williams JC: Branched chain organic acidurias. In Scriver CR, et al (eds): The Metabolic and
Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing Division, 2001,
pp 2125-2164.
69. Thompson GN, Chalmers RA, Holliday D: The contribution of protein catabolism to metabolic decompensation in
3-hydroxy-3-methylglutaric aciduria. Eur J Pediatr 1990;149:346-350.
70. van Hove JLK, Kahler G, Millington DS, et al: Intravenous L-carnitine and acetyl-L-carnitine in medium-chain-acyl-
coenzyme A dehydrogenase deficiency and isovaleric acidemia. Pediatr Res 1994;35:96-101.
71. van Hove JLK, Rutledge SL, Nada MA, et al: 3-Hydroxyisovalerylcarnitine in 3-methylcrotonyl-CoA carboxylase
deficiency. J Inher Metab Dis 1995;18:592-601.
72. Wilson WG, Audenaert SM, Squillaro EJ: Hyperammonemia in a preterm infant with isovaleric acidemia. J Inher
Metab Dis 1984;7:71.
73. Winokur PA, Vashistha K, Seshamani R: Isovaleric acidemia: A case report. Pediatrics 1978;61:902-903.
74. Yudkoff M, Cohn RM, Puschak R, et al: Glycine therapy in isovaleric acidemia. J Pediatr 1978;92:813-817.

PROTOCOL 7 — Mitochondrial Acetoacetyl-CoA Thiolase Deficiency (ß-Ketothiolase
Deficiency)

KETONEX ®-1 and KETONEX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
Beta-ketothiolases catalyze the reversible cleavage of ß-ketoacyl-CoA with a-CoA to form an acyl-CoA
with two fewer carbons and acetyl-CoA. Mitochondrial acetoacetyl-CoA thiolase interconverts
α-methylacetoacetyl-CoA to propionyl-CoA plus acetyl-CoA in essential isoleucine (ILE) catabolism
and acetoacetyl-CoA to two acetyl-CoAs in fatty acid oxidation (Figure F) (46).
Figure F. Isoleucine metabolism in mitochondrial acetoacetyl-CoA thiolase deficiency

The clinical features of mitochondrial acetoacetyl-CoA thiolase deficiency range from frequent
severe catabolic crises in infants to asymptomatic adults (46). The most common features are failure
to thrive, intermittent severe metabolic acidosis, and ketosis (9, 10) with hematemesis (6), melena (6,
46), and coma (21, 34) following upper respiratory or gastrointestinal infections or increased protein
intake. The episodes usually begin between 1 and 2 years of age and may occur every few months.
One patient expired with congestive cardiomyopathy at 8 years of age (18). Several siblings of
probands who were presumably affected died during acute episodes. Acute episodes usually resolve
with intravenous glucose and no permanent damage may result, although two patients had
developmental retardation and another is mentally retarded. Most patients are treated with moderate
restriction of ILE intake, avoidance of fasting, and L-carnitine administration, which greatly reduce or
eliminate severe episodes. Several patients have reported severe headaches beginning at 6 to
7 years of age (17) and 2 patients had ataxia (17). The father of 1 patient was shown to have the
same severe deficiency of enzyme activity and never had symptoms (46). In one case, the initial
diagnosis was of salicylate toxicity because of similar symptoms and a positive test for salicylates
(35).

With prompt correction of severe metabolic acidosis and ketosis and treatment with moderate restriction
of essential ILE and L-carnitine administration (7), prognosis and subsequent growth and development
are excellent for patients with mitochondrial acetoacetyl-CoA thiolase deficiency.
124 ß-Ketothiolase Deficiency © 2001 Ross Products Division

A. The Defect
1. Results from deficiency of mitochondrial acetoacetyl-CoA thiolase (3, 10, 11, 20, 21, 26-28,
34, 35).
B. The Disorder
1. Diagnostic studies should be conducted in any infant or child with recurring episodes of severe
ketosis, metabolic acidosis (6), hyperglycinemia (20, 23), ± hematemesis (6), and
± melena (6).
2. Studies should be conducted during acute illness.
C. Laboratory Studies
1. Analysis of urinary organic acids.
a. Elevations of the following metabolites are diagnostic:
1) α-methyl-ß-hyroxybutyric acid (3, 10, 11, 14, 31).
2) α-methylacetoacetic acid (3, 10, 11, 14).
3) Butanone.
4) Tiglylglycine (3, 10, 11).
2. Assay of acetoacetyl-CoA thiolase in fibroblasts (6, 38) or leukocytes (3, 11, 14, 21, 28, 38).
D. Prenatal Diagnosis
1. Measure activity of mitochondrial acetoacetyl-CoA thiolase in cultured amniocytes or chorionic
villus cells (46).

1. Restrict dietary ILE to amount that maintains normal urinary excretion of organic acids.
B. Provide Conditionally Essential Nutrient
1. Administer L-carnitine to maintain normal plasma free carnitine concentration > 30 µmol/L.
V. Nutrition Support During Acute Illness or at Diagnosis

1. Initiate nutrition support immediately on confirmation of diagnosis and control of metabolic
acidosis and ketosis.
2. Evaluate plasma concentrations of ILE, leucine (LEU), and valine (VAL) daily initially to
prevent deficiency.
B. Patients Without Severe Neurologic Involvement
1. Begin high-energy feeds (120-150 kcal/kg for infants, 80-100 kcal/kg for children, and
40-50 kcal/kg for adults) that supply adequate water (Table 7-1, p 113).
a. Depending on age and clinical status, feed patient by nipple, nasogastric tube,
intravenous infusion, or combine these methods.
1) For nipple or nasogastric feeds, use Ketonex (Table 7-2, p 133).
2) For intravenous feeds via central line, use hypertonic D-glucose and Liposyn ® II
3) For intravenous feeds via peripheral line, use isotonic glucose and Liposyn II
2. Introduce nutrition support with Ketonex (Table 7-2, p 133) with added source of L-LEU and
L-VAL as rapidly as possible. See Table 7-1, p 133, for Recommended LEU, VAL, Protein,
Energy, and Fluid Intakes.
3. Add ILE (Table 7-1, p 133) to Ketonex feeds when plasma ILE concentration reaches lower
limit of normal (50 µmol/L).
a. Calculate amount of infant formula, beikost, whole cow's milk, or table foods (Table 7-3,
p 133) required to fill ILE prescription.
b. Measure into Ketonex medical food mixture with disposable syringe if liquid infant formula
or cow's milk is used. Weigh powder on scale that reads in grams.
© 2001 Ross Products Division ß-Ketothiolase Deficiency 125

C. Comatose Patients
1. See Reference 34 for medical management.
2. Begin ILE-free parenteral or nasogastric feeding of amino acids and energy within 36 to
48 hours of initiation of dialysis using nitrogen-free (amino acid-free) dialysate.
a. See Table 7-1, p 133, for Recommended LEU, VAL, Protein, and Energy Intakes.
b. See Table7-2, p 133, for Ketonex composition.
3. Begin intravenous infusion of Liposyn II (Appendix 26, p A-28) and 10% D-glucose during
nasogastric feeding, continuing until major neurologic signs subside.
4. When plasma ILE reaches lower limit of normal (50 µmol/L), add L-ILE to Ketonex feeds.

A. Plasma Amino Acid Concentrations (30)
1. Maintain 2- to 4-hour postprandial plasma BCAA concentrations in ranges noted below when
measured by quantitative methods (modified from reference 30), or near lower limit of normal
range for age established by laboratory used.
ILE 50 - 105 0.6 - 1.4
LEU 50 - 185 0.6 - 2.4
VAL 130 - 318 1.5 - 3.7
in adults.
3. Maintain normal nutrition status (8).
5. Avoid prolonged fasting.
6. Maintain urine free of organic acids and ketones.
7. Prevent osteopenia (18).

A. ILE
1. Prescribe ILE intake that promotes goals of nutrition support (1-3, 7, 10, 11, 18, 26, 27, 36).
2. ILE requirements vary widely:
a. From patient to patient, depending on activity of acetoacetyl-CoA thiolase (26, 28).
1) Age.
2) Growth rate.
4) State of health.
3. Lowest values for age for ILE listed in Table 7-1, p 133, are suggested for initiating therapy.
a. Plasma ILE concentration.
b. Urine concentrations of organic acids.
d. With ILE, LEU, and VAL in normal range, plasma amino acids must be measured
frequently to prevent deficiency.
Warning: ILE, LEU, and VAL deficiencies result in adverse effects:
• ILE deficiency: Weight loss or no weight gain; redness of buccal mucosa;
fissures at corners of mouth; tremors of extremities; decreased plasma
cholesterol and ILE concentrations; increased plasma lysine,

phenylalanine, serine, tyrosine, and VAL concentrations; and skin
desquamation if deficiency is prolonged (42).
• LEU deficiency: Loss of appetite, apathy, irritability; weight loss or poor
weight gain; decreased plasma LEU concentration; and increased plasma
ILE, methionine, serine, threonine, and VAL concentrations (44).
• VAL deficiency: Poor appetite, drowsiness; excess irritability and crying
in infants; weight loss or decrease in weight gain; and decreased plasma
albumin concentration (43).
B. Carnitine
1. Prescribe adequate carnitine to maintain plasma free carnitine concentrations in normal range
(> 30 µmol/L).
2. Between 150 and 300 mg L-carnitine/kg may be required (3).
C. Protein
1. Prescribe, initially, amount greater than Recommended Dietary Allowances (RDAs) (2, 13)
(Table 7-1, p 133).
concentrations, osteopenia, and hair loss.
D. Energy
3. At diagnosis and during metabolic acidosis resulting from infection, energy needs may be 25%
to 40% higher than values listed in Table 7-1, p 133.
in children, weight loss in adults, depressed tolerance of ILE, and increased
plasma ILE concentration.
E. Fluid
1. Prescribe amount that will supply water requirements (Table 7-1, p 133) (5). Under normal
adults for each kcal ingested (5).
F. Sodium Bicarbonate
1. Administer sodium bicarbonate hourly when Acetest is 3+.
2. Administer 1 g hourly until Acetest is negative.

A. ILE
1. Calculate amount of infant formula with iron, beikost, whole cow' milk, or table foods
(Table 7-2, p 133) required to fill ILE prescription.
a. Low-iron infant formula, whole cow's milk, or evaporated milk should not be used as ILE
source for infants because of low iron content.
2. Measure liquid infant formula with disposable syringe. Weigh powdered infant formula on
scale that reads in grams.
3. Add beikost or table foods to gradually displace ILE provided by infant formula after infant is

4. Parents or patients may select any foods in prescribed Servings Lists for BCAA-Restricted
Diets (Protocol 5, pp 88-99) in specified amounts to fill diet prescription.
B. LEU and VAL
1. Calculate approximate amounts of LEU and VAL provided by infant formula with iron, beikost,
whole cow's milk, or table foods (Table 7-2, p 133).
2. Subtract amount determined above from total LEU and VAL prescription.
3. Supply any remaining prescribed LEU and VAL as individual pure solutions. Add supplemental
LEU and VAL (Appendix 26, p A-28) only if plasma concentrations are below normal.
a. Mix weighed amounts of L-LEU and L-VAL powders with boiled, cooled water to make
volume of each that yields 10 mg/mL (eg, 1 g with enough water to yield 100 mL).
b. Refrigerate solutions in separate, sterilized, closed containers until used. Discard unused
suspensions after 1 week, if not frozen.
c. Measure solutions into medical food mixture with disposable syringes.
C. Protein
(Table 7-2, p 133) required to fill the ILE prescription.
2. Subtract amount determined above from protein prescription
3. Supply remaining prescribed protein with Ketonex (Table 7-2, p 133).
a. Ketonex-1 is for infants and toddlers and Ketonex-2 is for children, adolescents, and
adults.
b. Weigh Ketonex powder on scale that reads in grams because of variability of household
c. See Table 5-2 (p 86, footnote 3) for approximate packed weight of Ketonex powder in
D. Carnitine
1. Calculate amount of carnitine provided by Ketonex (Table 5-2, p 86) and infant formula with
iron (Appendices 4 through 7, pp A-4 to A-7).
2. Supply remaining carnitine prescribed with L-carnitine (Appendix 26, p A-28).
E. Energy
(Table 7-2, p 133) required to fill ILE prescription plus energy provided by Ketonex (Table 7-2,
p 133) required to fill protein prescription.
2. Subtract amount of energy supplied by these sources from energy prescription.
a. Do not use corn syrup or table sugar for infants because of osmolarity they yield.
1. Add sufficient boiled, cooled water to infant formula, Ketonex, L-carnitine, and carbohydrate (if
needed) to yield prescribed volume.
may destabilize emulsion. May also be mixed in tightly closed container by shaking
4. Do not use terminal sterilization because of Maillard reaction (Practical Aspects of Nutrition
Support, p viii).
before feeding.
8. For children and adults, chill Ketonex medical food mixture to improve taste.
G. Diet Guide
each diet change.
2. Feed young infants 6 to 8 times daily (15, 16, 19, 37).
3. Feed children and adults 4 to 6 times daily (15, 16, 19, 37).
4. Avoid prolonged fasting.

a. See Table 7-2, p 133, for composition of Ketonex, infant formulas, and whole cow's milk.
a. See Table 5-2, p 86, and Appendices 4 through 7, pp A-4 to A-7, for complete nutrient
composition of Ketonex and infant formulas.
not available.
c. If Ketonex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
foods and laboratory tests indicate need.
1) See Appendix 11, p A-10, for composition of supplements.
B. Osmolarity
b. Osmolarity per gram of Ketonex is listed in Appendix 19, p A-21.
2. If osmolarity is > 450 mosm /kg H2O for neonates, > 750 mosm/L for children, >
1,000 mosm/L for adults, or is greater than tolerated by patient, increase water content of
prescribed medical food mixture and recalculate its osmolarity (25, 41).
renal solute load.
recalculate.

A. Plasma BCAA Concentrations
1. Initial:
a. Evaluate daily by quantitative methods to make sure that concentrations stabilize in low
normal range.
2. Ongoing:
b. Evaluate twice monthly by quantitative methods until patient is 6 months old and monthly
thereafter.

3. Unacceptable amino acid concentrations.
a. If plasma ILE, LEU, or VAL concentration is not detected and patient has ingested full
prescription:
plasma concentrations in 3 days.
2) If plasma ILE, LEU, or VAL concentration continues undetected, repeat above process
b. If plasma ILE concentration is < 50 µmol/L, plasma LEU concentration is < 50 µmol/L, or
plasma VAL concentration is < 130 µmol/L, and the patient has ingested full prescription:
1) Increase prescribed amount of amino acid that is low by 5% to 10% and reevaluate
plasma concentration in 1 week.
2) If plasma ILE, LEU, or VAL concentration continues to be low, repeat above process
c. If plasma ILE concentration is > 105 µmol/L, plasma LEU concentration is > 185 µmol/L,
or plasma VAL concentration is > 318 µmol/L, and patient is not ill and has not ingested
more or less protein and energy than prescribed:
1) Decrease prescribed amount of elevated amino acid by 5% to 10% and reevaluate
plasma concentration in 1 week.
2) If plasma ILE, LEU, or VAL concentration continues high, repeat above process until
B. Urine Ketoacids by Ketostix ® (17)
1. Evaluate daily to 6 months of age and twice weekly thereafter.
2. If patient is ill, evaluate daily.
3. Urine should be free of ketoacids at all times (negative Ketostix).
4. If urine contains ketoacids (positive Ketostix):
a. Immediately obtain blood sample for evaluation of ILE concentration by quantitative
methods.
b. Brief metabolic physician immediately on patient's illness.
C. Plasma Carnitine Concentration
1. Analyze plasma free carnitine concentration monthly during first 6 months of life and every
3 months thereafter.
2. If plasma free carnitine concentration is < 30 µmol/L, increase L-carnitine administered by 5%
to 10% and reevaluate in 1 week.
3. If plasma free carnitine concentration remains low, repeat above process until value is in
normal range.
D. Protein Status
1. Evaluate plasma transthyretin every 3 months until patient is 1 year of age and every 6
months thereafter (Appendix 17, p A-18, for standards).
concentration in 1 month. If ILE concentration is in treatment range, use Ketonex to
increase protein.
normal range.
E. Iron Status

a. Hemoglobin and hematocrit concentrations should be evaluated every 3 months in infants
and every 6 months in toddlers (Appendix 17, p A-18, for standards).
F. Growth Status
a. Measure monthly to 1 year and every 3 months thereafter. Plot measurements on NCHS
growth charts.
a. Increase protein and energy prescriptions by 5% to 10% and remeasure in 1 month.
achieved.
G. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of BCAAs, protein, and energy before each blood test.
not available.
H. Clinical Summary

A. Example 1
Intakes from Table 7-1, p 133 and nutrient contents from Table 7-2, p 133.
ILE 100 mg/kg x 3.0 kg = 300 mg
LEU ≥ 180 mg/kg x 3.0 kg = > 540 mg
VAL ≥ 100 mg/kg x 3.0 kg = > 300 mg
Ketonex-1 32 g 0 0 0 4.8 154
Similac With Iron RTF 405 mL 304 583 336 5.7 275
Total per day 304 583 336 10.5 429

Total per kg 101 194 112 3.5 143
is ≤ 100 mosm.

B. Example 2
Nutrient Intakes from Table 7-1, p 133 and nutrient contents from Table 7-2, p 133.
ILE 750 mg/day
LEU > 1,000 mg
VAL > 750 mg
Protein 30 g
Energy 1,300 kcal
Fluid 1,300 mL
Ketonex-2 42 g 0 0 0 12.6 172
Whole cow's milk 144 mL 295 478 327 4.9 91
Food List Servings

Breads/Cereals 14 252 490 350 7.0 420
Fats 4 28 40 28 0.4 280
Fruits 4 68 100 88 2.4 300
Vegetables 5 110 150 120 3.0 75
Total per day 753 1,258 913 30.3 1,338
C. Example 3
Establish and fill prescription for 15-year-old boy weighing 60 kg using Recommended Daily
Nutrients Intakes from Table 7-1, p 133 and nutrient contents from Table 7-2, p 133.
ILE 1,300 mg/day
LEU < > 1,650 mg
VAL < > 1,300 mg
Protein 65 g
Energy 2,800 kcal
Fluid 2,800 mL
Ketonex-2 122 g 0 0 0 36.6 500
Whole cow's milk 314 mL 644 1,042 713 10.6 198
Add water to make 1,000 mL (34 fl oz). Offer additional fluid ad libitum daily.
Food List Servings

Breads/Cereals 20 360 700 500 10.0 600
Fats 12 84 120 84 1.2 840
Fruits 6 102 150 132 3.6 450
Vegetables 5 110 150 120 3.0 75
Free Foods B 3 0 0 0 0.0 165
Total per day 1,300 2,162 1,549 65.1 2,828

A. Rationale
1. Febrile illness and trauma are life-threatening if not diagnosed and treated promptly (47).
B. Management of Nutrition Support
1. See Section V, Nutrition Support During Acute Illness or at Diagnosis, p 124.

ß-Ketothiolase Deficiency
Age Nutrient
ILE1 LEU1 VAL1 Protein2 Energy2 Fluid3
(mg/kg) (mg/kg) (mg/kg) (g/kg) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 90 - 140 > 180 > 100 3.50 - 3.00 120 (145 - 95) 150 - 125
3 to < 6 mo 85 - 135 > 160 > 90 3.50 - 3.00 115 (145 - 95) 160 - 130
6 to < 9 mo 80 - 135 > 150 > 80 3.00 - 2.50 110 (135 - 80) 145 - 125
9 to < 12 mo 75 - 125 > 140 > 70 3.00 - 2.50 105 (135 - 80) 135 - 120
(mg/day) (mg/day) (mg/day) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 750 - 1,000 > 1,000 > 750 > 30 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 850 - 1,100 > 1,150 > 850 > 35 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 1,000 - 1,300 > 1,300 > 1,000 > 40 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 1,200 - 1,500 >1,900 > 1,800 > 50 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 1,000 - 1,300 > 1,300 > 1,000 > 55 2,100 (1200 - 3000) 1,200 - 3,000
> 19 yr 1,000 - 1,300 > 1,330 > 1,000 > 60 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 1,000 - 1,300 > 1,900 > 1,150 > 55 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 1,300 - 1,650 > 1,650 > 1,300 > 65 2,800 (2100 - 3900) 2,100 - 3,900
> 19 yr 1,300 - 1,650 > 1,650 > 1,300 > 70 2,900 (2000 - 3300) 2,000 - 3,300
1
From references 1, 12, and 24. Initiate prescription with lowest recommended intake for age. Modify prescription
based on frequently obtained plasma values and growth in infants and children and frequently obtained plasma
values and weight maintenance in adults.
2
3
children and adults for each kcal ingested. Fluid intake should be higher during illness to enhance urinary ketoacid
excretion.
1
TABLE 7-2. Serving Lists for ILE-Restricted Diets: Average Nutrient Content per Serving
Food List Nutrient

ILE LEU VAL Protein Energy
Fats 7 10 7 0.1 70
Fruits 17 25 22 0.6 75
Vegetables 22 30 24 0.6 15
2
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 108 173 140 1.86 68
2
Ketonex®-1 powder, 100 g 0 0 0 15.00 480
Ketonex®-2 powder, 100 g 0 0 0 30.00 410
2
Similac ® With Iron Infant Formula, Ready to Feed, 100 mL 75 144 83 1.40 68
3
1
Reference 12
2
3

TABLE 7-3. ß- Ketothiolase Deficiency Clinical Summary Sheet
134 ß-Ketothiolase Deficiency
Date of Birth: __________/__________/__________

Mo Day Year

1 1 1
Length/ Weight Head ILE LEU VAL Free Carn Hgb Hct Ferritin Transthyretin Ketostix ® ILE LEU VAL CARN Protein Energy
Height Circum or Acetest
(mo/d/yr) (yrs/mos) (cm) (kg) (cm) (µmol/L) (g/dL) (%) (ng/mL) (mg/dL) (mg) (mg) (mg) (mg) (g) (kcal)
1
Indicate if µmol/L or mg/dL.
REFERENCES
1985, 115-135.
3. Aramaki S, Lehotay D, Sweetman L, et al: Urinary excretion of 2-methylacetoacetate, 2-methyl-3-hydroxybutyrate
and tiglyglycine after isoleucine loading in the diagnosis of 2-methylacetyl-CoA thiolase deficiency. J Inher Metab
Dis 1991;14:63-74.
Dis 2000;23 (Suppl 1):A29.
1996.-
6. Bennett MJ, Littlewood JM, MacDonald A, et al: A case of ß-ketothiolase deficiency. J Inher Metab Dis 1983;6:157.
7. Brown GK, Hunt SM, Mitchell DK, Danks DM: Profound neurological illness, relieved by protein restriction, in a
baby with a transient disturbance in the metabolism of ingested isoleucine. Eur J Pediatr 1987;146:363-369.
9. Cromby CH, Manning NJ, Pollitt, et al: 6-Methyluracil excretion in 2-methylacetoacetyl-CoA thiolase deficiency and
in two children with an unexplained recurrent ketoacidaemia. J Inher Metab Dis 1994;17:81-84.
10. Daum RS, Lamm PH, Mamer OA, Scriver CR: A "new" disorder of isoleucine catabolism. Lancet
1971;2:1289-1290.
11. Daum RS, Scriver CR, Mamer OA, et al: An inherited disorder of isoleucine catabolism causing accumulation of
α-methylacetoacetate and α-methyl-ß-hydroxybutyrate, and intermittent metabolic acidosis. Pediatr Res
1973;7:149-160.
14. Gompertz D, Saudubray JM, Charpentier C, et al: A defect in L-isoleucine metabolism associated with α-methyl-ß-
hydroxybutyric acid and α-methylacetoacetic aciduria: Quantitative in vivo and in vitro studies. Clin Chim Acta
1974;57:269-281.
17. Halvorsen S, Stokke O, Jellum E: A variant form of 2-methyl-3-hydroxybutyric and 2-methylacetoacetic aciduria.
Acta Paediatr Scand 1979;68:123-128.
18. Henry CG, Strauss AW, Keating JP, Hillman RE: Congestive cardiomyopathy associated with ß-ketothiolase
deficiency. J Pediatr 1981;99:754-757.
20. Hillman RE, Keating JP: Beta-ketothiolase deficiency as a cause of the "ketotic hyperglycinemia syndrome."
Pediatrics 1974;53:221-225.
21. Hiyama K, Sakura N, Matsumoto T, Kuhara T: Deficient beta-ketothiolase activity in leukocytes from a patient with
2-methylacetoacetic aciduria. Clin Chim Acta 1986;155:189-194.
23. Keating JP, Fergin RD, Tenenbaum SM, Hillman RE: Hyperglycinemia with ketosis due to a defect in isoleucine
metabolism: A preliminary report. Pediatrics 1972;50:890-895.
1982.
26. Merinero B, Perez-Cerda C, Garcia MJ, et al: ß-ketothiolase deficiency: Two siblings with different clinical
conditions. J Inher Metab Dis 1987;10 (Suppl 2):276-278.
27. Middleton B, Bartlett K, Romanos A, et al: 3-Ketothiolase deficiency. Eur J Pediatr 1986;144:586-589.
28. Middleton B, Gray RGF, Bennett MJ: Two cases of ß-ketothiolase deficiency: A comparison. J Inher Metab Dis
1984;7 (Suppl 2):131-132.

30. Picone TA, Benson JD, Moro G, et al: Growth, serum biochemistries, and amino acids of term infants fed formulas
with amino acid and protein concentrations similar to human milk. J Pediatr Gastroenterol Nutr 1989;9:351-360.
31. Pollitt RJ: The occurrence of substituted 3-methyl-3-hydroxyglutaric acids in urine in propionic acidemia and in
ß-ketothiolase deficiency. Biomed Mass Spec 1983;10:253-257.
1955;56:231-251.
34. Riudor E, Ribes A, Perez-Cerda C, et al: Metabolic coma with ketoacidosis and hyperglycaemia in
2-methylacetoacetyl-CoA thiolase deficiency. J Inher Metab Dis 1995;18:748-749.
35. Robinson BH, Sherwood WG, Taylor J, et al: Acetoacetyl-CoA thiolase deficiency: A cause of severe ketoacidosis
in infancy simulating salicylism. J Pediatr 1979;95:228-233.
36. Sabetta G, Bachmann C, Giardini O, et al: ß-ketothiolase deficiency with favourable evolution. J Inher Metab Dis
1987;10:405-406.
38. Schutgens RBH, Middleton B, Blij JFvd, et al: ß-ketothiolase deficiency in a family confirmed by in vitro enzymatic
assay in fibroblasts. Eur J Pediatr 1982;139:39-42.
Publisher, 1976.
1983;7:280-288.
Clin Nutr 1964;15:313-321.
1959;97:186-191.
Child 1961;102:157-162.
1989;143:828-832.
46. Sweetman L, Williams JC: Branched-chain-organic acidurias. In Scriver CR, et al (eds): The Metabolic and
pp 2125-2164.
1977;30:1269-1280.

PROTOCOL 8 — Homocystinuria

HOMINEX ®-1 and HOMINEX ®-2 Amino Acid-Modified Medical Foods
I. Introduction (14, 27)
Intact protein contains from 0.3% to 5.0% of the essential amino acid methionine (MET) (33). Some
dietary MET is used by the body for tissue protein synthesis, but most is utilized through the
transsulfuration pathway (Figure G). The first step in the transsulfuration pathway is synthesis of
S-adenosylmethionine (SAM), a reaction catalyzed by methionine-S-adenosyltransferase (MAT).
Impaired MAT activity results in hypermethioninemia and variable clinical expression from sulfurous
breath odor to mental retardation. Biologically important compounds that obtain their methyl group
from SAM include creatine, choline and phosphatidylcholine, methylated DNA and RNA, and
epinephrine. S-adenosylhomocysteine is an intermediary product in the transsulfuration pathway and
is hydrolyzed to homocysteine (27).
Tissue protein catabolism Dietary protein
Glycine Serine Methionine†‡ Tissue protein synthesis
Tetrahydrofolate ATP
5,10-Methylene
5-Methyltetra-
tetrahydrofolate hydrofolate
homocysteine Methionine-S-adenosyltransferase
methyl- Dimethylglycine (MAT)
5,10-Methylene
tetrahydrofolate transferase
reductase CH3-B 12
Betaine-homocysteine
5-Methyltetrahydrofolate methyltransferase
Betaine
S-Adenosylmethionine
Choline
‡ ‡
Homocystine Homocysteine
Cystathionine ß-synthase (CBS), B 6

Serine †
Accumulates in MAT deficiency, if untreated.
‡
Accumulates in CBS deficiency, if untreated
(n) = several steps
Adenosylhomocysteine
= site of enzyme malfunction
Cystathionine
Cystathionase, B 6
Cystine Cysteine + α-Ketobutyrate → Propionyl CoA → Succinyl CoA

(n)
SO4 (n)
Taurine
Figure G. Methionine metabolism in homocystinuria

Four possible pathways are open to homocysteine. It can be remethylated to form MET through two
different enzymatic reactions. In one reaction, the methyl group is derived from betaine and is
catalyzed by betaine-homocysteine methyltransferase. The second reaction requires
5
N -methyltetrahydrofolate as a methyl donor and methylcobalamin (CH3-B12) as coenzyme (Figure G)
(47). The enzyme catalyzing this reaction is 5-methyltetrahydrofolate-homocysteine
methyltransferase. The third pathway open to homocysteine is spontaneous oxidation to homocystine
138 Homocystinuria © 2001 Ross Products Division
(Figure G). This reaction occurs only when homocysteine is present in tissue in abnormal amounts.
Homocystine is not
© 2001 Ross Products Division Homocystinuria 139

further metabolized. Most homocysteine is metabolized by cystathionine ß-synthase (CßS) to
cystathionine using serine as co-substrate and pyridoxal phosphate as coenzyme. Cystathionine is
then hydrolyzed to cysteine and α−ketobutyrate. The enzyme cystathionase, for which pyridoxal
phosphate is coenzyme, is required for this reaction (Figure G). A deficiency of cystathionase results
in cystathioninuria, which has no pathologic consequence. Alpha-ketobutyrate is converted to
propionyl-CoA, which is carboxylated to methylmalonyl-CoA and isomerized to succinyl-CoA, a Krebs-
cycle intermediate. L-Cysteine is catabolized to pyruvate, NH3, and H2S.
Defects in the function of CßS or 5-methyltetrahydrofolate-homocysteine methyltransferase result in
classical homocystinuria. Impaired activity of the latter enzyme may be caused by failure to
synthesize methylcobalamin from vitamin B12 or by a deficiency in 5, 10 methylenetetrahydrofolate
reductase, as well as by mutations in the apoenzyme. Several different defects impair the uptake,
transfer, and conversion of dietary vitamin B12 to methylcobalamin.
The most common form of homocystinuria is caused by a deficiency of CßS. Some forms are
responsive to vitamin B6 while others are not. Severely impaired enzyme function produces
accumulation of plasma homocyst(e)ine and MET and decreased cyst(e)ine in cells and physiologic
fluids. If this disorder is not treated early in life, skeletal changes, dislocated lenses, intravascular
throboses (8), osteoporosis (31), malar flushing, and, in some patients, mental retardation will occur.
In a large survey of patients with homocystinuria due to CßS deficiency, only 13% were vitamin B6
responsive (28). The mechanism involves stabilizing CßS to biological degradation. The more
residual enzyme activity present, the more dramatic the response to vitamin B6. Hypermethioninemia
may not be present in the newborn if the activity of CßS is greater than 15%.
Management of CH3-B12 deficiency or impaired methyl transfer with homocystinuria does not require
MET-restricted diets. Rather, pharmacologic amounts of vitamin B12 (47), folate, choline, or betaine
are added, depending on the primary defect.
Pharmacologic doses of pyridoxine should be tried in all patients with hypermethioninemia and
homocystinemia. In newborns and early childhood, 25 to 100 mg per day should be tried for a 4-week
interval before MET restriction. In older children and adults, oral pyridoxine (1 g daily) should be tried.
Weeks may be required for a biochemical response to occur. If the plasma MET and homocysteine
concentrations are reduced, the amount of pyridoxine should be gradually lowered until the minimum
dose required to maintain biochemical normality is reached. Doses of 25 to 750 mg day have been
required for some patients. Excess vitamin B6 for prolonged periods of time may cause peripheral
neuropathy (5, 36) or rhabdomyolysis (38); consequently, if it is not helpful, vitamin B6 should be
discontinued. Betaine supplements will assist in maintaining postprandial plasma homocysteine
concentrations in the near-normal range in individuals (42, 48).
Patients who do not respond completely to pyridoxine will require a MET-restricted diet supplemented
with L-cysteine. L-cysteine becomes an essential amino acid in homocystinuria (Figure G). If plasma
folate concentrations are below normal owing to excess consumption in remethylating homocysteine
to MET, folate should be added as a supplement.
Prenatal diagnosis may be provided by direct enzyme assay of amniotic fluid cells or by DNA analysis
if the mutations are known.

In a retrospective study of 629 patients with CßS deficiency, MET restriction initiated neonatally
prevented mental retardation, decreased the frequency of lens dislocation, and reduced the incidence
of seizures (28). Newborn screening and treatment of 25 cases in Ireland also supports the efficacy of
nutrition management (49). Pyridoxine treatment of vitamin B6-responsive patients decreased the rate
of thromboembolic events (28). Weight and height in a girl with homocystinuria treated from the 9th
day of life was at the 90th percentile (3). Hispanic male twins born at 38 weeks gestation with
homocystinuria grew well during the entire 1st year of life while on nutrition support. Protein intake of
these two subjects averaged 3.7 g/kg/day during the 1st 6 months of life and 2.6 g/kg/day during the
2nd 6-months of life. Energy intake during the 1st 6 months averaged 131 kcal/kg and 100 kcal/kg
during the 2nd 6 months (2).
Cysteine deficiency manifested as abnormally low plasma cysteine concentrations, elevated plasma
MET concentrations, and weight loss in homocystinuria has been reported (35). Up to
150 mg L-cysteine/kg/day may be required to maintain normal plasma cysteine concentrations.
Elevated plasma copper and ceruloplasmin concentrations were found in patients with homocystinuria
(13, 50). No relationship to plasma homocysteine could be found. The twins described

above had elevated serum copper concentrations of 151 and 144 µg/dL at about 3 months of age (2).
Low plasma selenium concentration and erythrocyte glutathione peroxidase activity were found in a
child with homocystinuria treated with a medical food free of selenium (45).
Vitamin A absorption tests were carried out in untreated patients with homocystinuria by measuring
the elevation in serum retinol concentration after administration of vitamin A alcohol. The explanation
proposed for the resulting subnormal serum retinol elevation was that retinol was oxidized by -SH
groups excreted into the gut (3). Of the 8 plasma retinol values obtained on the twins studied, 1 was
< 20 µg/dL and 5 were between 20 and 30 µg/dL. According to parental report, vitamin A intake was
always more than adequate (1.20-5.58 times RDA for age). Serum transthyretin concentrations were
all below 20 mg/dL (marginal) and 2 values obtained were below 15 mg/dL (deficient) (2).
Fasting serum folate concentrations in untreated patients with homocystinuria were abnormally low.
Two of these subjects were treated with 20 mg folate daily, which led to a decrease in urinary
homocystine excretion (11). Severe folate deficiency was found in an untreated infant with
homocystinuria who was receiving diluted boiled cow's milk for an episode of gastroenteritis (3).
Excessive utilization of 5-methyltetrahydrofolate in remethylation of homocysteine to form MET is
proposed as a reason for folate deficiency in untreated patients (14). The twins reported had adequate
hemoglobin concentrations after 4 months of age, and mean corpuscular volume was normal (2).
Most clinicians who treat individuals with homocystinuria believe that patients should be kept on diet
indefinitely. Termination of diet after growth is achieved may lead to thromboembolisms and ciliary
muscle laxity with lens dislocation. Where initiation or maintenance of nutrition support is not possible,
acetylsalicylic acid (1 g daily), betaine and dipyridamole (100 mg daily) increase platelet survival time
and decrease thrombotic events. Vitamin B6 in pharmacological doses should be tried and folate
should be given (14).

A. The Defect
1. Homocystinuria without methylmalonic aciduria may result from defect in any of at least
3 enzymes (14, 27).
a. Methylenetetrahydrofolate reductase.
b. 5-Methyltetrahydrofolate-homocysteine methyltransferase.
c. CßS.
1) Abnormalities in this enzyme may respond to pharmacologic doses of vitamin B6
(25-100 mg/day for 1-month trial in neonates).
2) Administer smallest amount of vitamin B6 daily that maintains normal concentrations
of plasma MET and homocyst(e)ine (5, 26, 38).
3) Patients who respond to vitamin B6 therapy usually do not require nutrition support.
1. MET concentration > 1 mg/dL by bacterial inhibition assay or positive urine nitroprusside-
cyanide test requires differential diagnosis.
C. Differential Diagnosis (14, 27).
1. Differential diagnosis will reveal false-positives and identify specific enzyme defects.
3. This protocol addresses nutrition support of patients with vitamin B6 non-responsive CßS
deficiency.

1. Restrict dietary MET to amount tolerated by patient to maintain treatment plasma MET
concentration (1, 14).
1. Supplement dietary cystine (CYS) as necessary to maintain normal plasma CYS
concentration (35)

V. Establish Goals of Long Term Nutrition Support (14)
A. Plasma MET Concentration
1. Maintain 2- to 4-hour postprandial plasma MET concentration between 18 and 45 µmol/L
when measured by quantitative methods or within range of normal for age in laboratory used
(14)
a. In practice, obtaining blood 2 to 4 hours postprandially is not always possible. Acceptable
local standards should be developed if plasma amino acids are evaluated at other times
(Practical Aspects of Nutrition Support, p viii).
2. Opinions vary as to best concentration of plasma MET and CYS to support normal growth and
development in infants and children.
a. In this protocol, concentrations as close to normal as possible are recommended.
B. Plasma CYS Concentration
1. Maintain 2- to 4-hour postprandial plasma CYS concentration between 25 and 50 µmol/L, or in
normal range for age as established by laboratory used.
C. Blood Homocystine Concentration
1. Maintain concentration of homocystine in blood at < 12 µmol/L.
D. Growth, Development, and Nutrition Status
1. Support normal growth rate in infants and children; maintain appropriate weight for height in
adults.
3. Maintain normal nutrition status (4, 10, 11).
E. Other Manifestations
1. Prevent dystonia (7, 21), thromboembolic disease (8, 12), gastrointestinal disease (20),
bleeding tendency (29), and pancreatitis (32).

A. MET
1. Prescribe MET intake that promotes goals of nutrition support (1, 14, 23).
2. MET requirements vary widely:
a. From patient to patient, depending on activity of CßS.
1) Age.
2) Growth rate.
4) State of health.
3. Lowest values for age listed in Table 8-1, p 148, are suggested for initiating therapy.
4. Frequent monitoring of plasma MET concentration is essential to assess patient's changing
requirements (Section IX, Suggested Evaluation of Nutrition Support, p 144).
Warning: MET deficiency results in adverse effects (43):
Decreased plasma MET concentration.
Increased concentrations of plasma phenylalanine, proline, serine, threonine,
and tyrosine.
Decreased plasma cholesterol concentration.
Failure to thrive in infants and children and weight loss in adults.
B. CYS
1. Prescribe CYS intake that maintains treatment plasma CYS concentration (35).
2. Lowest value for CYS for each age group listed in Table 8-1, p 148, is suggested to start
therapy.
3. Changing requirements of patient are determined by frequent monitoring of plasma CYS
concentration.
a. Prescribe CYS above amount supplied by Hominex and beikost or table foods only if
plasma CYS concentration is below normal.
Warning: CYS deficiency will result in adverse effects (35):
Elevated plasma MET and homocystine concentrations.
Decreased plasma CYS concentration.
Failure to thrive in infants and children and weight loss in adults.
C. Folate
1. Prescribe amount that maintains plasma or erythrocyte folate concentration in normal
range (11, 18) (Appendix 17, p A-18).
2. Daily supplement of 500 to 1000 µg may be required (11).
D. Protein
(Table 8-1, p 148).
Warning: Inadequate protein intake will result in failure to thrive in infants, poor growth
in children, weight loss in adults, low plasma transthyretin concentrations,
osteopenia, hair loss, and decreased MET tolerance.
E. Energy
2. Requirements vary and may be greater than normal when L-amino acids supply majority of
protein equivalent (34).
in children, and weight loss in children and adults. Weight loss will result in
elevated plasma MET concentration as result of protein catabolism. Poor
growth will result in lower than expected tolerance of MET.
F. Betaine (Appendix 26, p A-28 — Cystadane™)
1. Prescribe amount that will blunt plasma homocyst(e)ine response to meals (42, 48).
2. 3 g betaine 2 to 3 times daily with meals resulted in significant decline in plasma homocystine
concentration and increase in plasma MET concentrations (48).
G. Fluid

A. MET
1. Calculate amount of infant formula with iron, human milk, beikost, whole cow's milk, or table
foods (Table 8-2, p 148) required to fill MET prescription.
a. Low-iron infant formula, whole cow's milk, or evaporated milk should not be used as MET
2. Measure liquid infant formula, human milk, or whole cow's milk with disposable syringe.
3. Add beikost or table foods (Table 8-2, p 148) to gradually displace MET provided by infant
formula or human milk after infant is 3 to 4 months old or is developmentally ready.
4. Parents or patients may select any food in prescribed food lists (Table 8-3, pp 149-161) in
specified amounts to fill diet prescription.

B. Protein
1. Calculate amount of protein provided by infant formula with iron, human milk, beikost, whole
cow's milk, or table foods (Table 8-2, p 148) required to fill MET prescription.
3. Supply remaining prescribed protein with Hominex (Table 8-2, p 148).
a. Hominex-1 is for infants and toddlers and Hominex-2 is for children, adolescents, and
adults.
b. Weigh Hominex powder on scale that reads in grams because of variability of household
c. See Table 8-4 (p 162, footnote 3) for approximate packed weight of Hominex powder in
C. CYS
1. Calculate approximate amount of CYS provided by infant formula with iron, human milk,
beikost, whole cow's milk, or table foods (Table 8-2, p 148) required to fill MET prescription.
2. Calculate amount of CYS supplied by Hominex (Table 8-2, p 148) required to fill protein
prescription.
3. Added together, values calculated in C1 and C2 should fall within range of CYS intake
recommended in Table 8-1, p 148.
4. Add supplemental L-CYS (Appendix 26, p A-28) only if plasma CYS concentration is below
normal
a. Mix weighed amount of L-CYS with boiled, cooled water to yield 10 mg/100 mL
(eg, 1.0 mg L-CYS with enough water to yield 100 mL).
b. Refrigerate suspension in sterilized, closed container until used. Discard unused
suspension after 1 week, if not frozen.
c. Shake well before using. Measure L-CYS suspension into medical food mixture with
disposable syringe.
1) L-cystine is not very soluble in water (11 mg/100 mL).
D. Folate
1. Administer in 3 equal doses daily.
a. A prescription is required for folic acid when given in excess of 400 µg/day.
2. Crush folic acid tablet and mix prescribed dose with applesauce or other fruit purées.
E. Energy
1. Calculate energy provided by infant formula with iron, human milk, beikost, or table foods and
Hominex (Table 8-2, p 148) required to fill MET and protein prescriptions.
2. Subtract amount determined above from energy prescription.
F. Betaine (Appendix 26, p A-28)
1. Mix with medical food mixture to administer.
G. Fluid and Mixing Instructions
1. Add sufficient boiled, cooled water to infant formula or human milk, Hominex, carbohydrate (if
needed), and L-CYS suspension (if needed) to yield prescribed volume. Tap water may
replace boiled, cooled water when preparing Hominex for older infants, children, and adults.
may destabilize emulsion. May also be mixed in sterilized, tightly closed container by

8. For children and adults, chill Hominex medical food mixture to improve taste.
H. Diet Guide
each diet change.
2. Feed young infants 6 to 8 times daily (16, 17, 19, 37).
3. Feed older infants, children, and adults 4 to 6 times daily (16, 17, 19, 37).

a. See Table 8-2, p 148, for composition of infant formulas, human milk, whole cow's milk
and Hominex.
a. See Table 8-4, p 162, for composition of Hominex and Appendices 4 through 7, pp A-4 to
not available.
c. If Hominex mixture provides < 100% of RDIs for infants and < 75% for children and
supplements).
B. Osmolarity
b. Osmolarity per gram of Hominex is listed in Appendix 19, p A-21.
mixture and recalculate its osmolarity (24, 25, 41).
renal solute load.
recalculate.

A. Plasma MET, CYS, and Homocystine Concentrations
1. Initial:
approximate dietary MET and CYS requirements are known (14).
b. Unless plasma samples are immediately deproteinized after drawing, CYS will form
disulfide bridges with protein and be precipitated with protein, resulting in plasma CYS
concentration that appears below normal.
2. Ongoing:
b. Evaluate plasma MET, CYS, and homocystine concentrations by quantitative methods
weekly until 6 months of age and monthly when concentrations are in treatment range
(14).
3. Unacceptable MET concentrations:
a. If plasma MET concentration is not detected and patient has ingested full prescription:
1) Add 20 mg to prescribed MET and reevaluate plasma MET concentration in 7 days.
2) If plasma MET concentration continues undetected, repeat above process until value
b. If plasma MET concentration is > 45 µmol/L and patient has ingested full prescription:
1) Subtract 5% to 10% from prescribed MET and reevaluate plasma MET concentration
in 7 days.
2) If plasma MET concentration continues > 45 µmol/L, repeat above process until value
B. Protein Status
concentration in 1 month. If plasma MET, CYS, and homocysteine concentrations are in
treatment range, use Hominex to increase protein.
C. Iron Status
D. Erythrocyte Folate Status
1. Evaluate every 3 months in infants and twice yearly thereafter.
a. Maintain concentration in normal range of ≥ 200 ng/mL (18).
b. If erythrocyte folate concentration falls to < 200 ng/mL:
1) Supplement with 500 µg folate/day.
2) Evaluate erythrocyte folate concentration in 1 month.

E. Growth Status
achieved.
F. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of MET, CYS, protein, and energy before each blood test.
not available.
G. Clinical Summary
A. Example 1
Establish and fill prescription for 1-month-old infant weighing 4 kg using Recommended Daily
MET 15 mg/kg x 4 kg = 60 mg/day
CYS1 300 mg/kg x 4 kg = 1,200 mg
Folate = 500 µg
Protein 3.5 g/kg x 4 kg = 14 g
Energy 120 kcal/kg x 4 kg = 480 kcal
Fluid 150 mL/kg x 4 kg = 600 mL
Betaine 1g x 4 kg = 4g
1
Add only if plasma CYS concentration is below normal.
Medical Food Mixture Measure MET CYS Protein Energy
Hominex-1 78 g 0 351 11.7 374
Similac With Iron Ready to Feed 171 mL 60 32 2.4 116
1 2
L-Cystine 82 mL 0 820 0.0 0
Total per day 60 1,203 14.1 490

Total per kg 15 300 3.5 122
is 100 mosm.
1
Suspension is 10 mg/mL (1 g L-cystine with water added to make 100 mL).
2

B. Example 2
MET 130 mg/day
CYS1 1,300 mg
Folate 1 mg
Protein 30 g
Energy 1,300 kcal
Fluid 1,300 mL
Betaine 6g
1
Hominex-1 150 g 0 675 22.5 720
L-Cystine1 50 mL2 0 500 0.0 0
Food List Servings

Fats 3 6 0 0.3 150
Fruits 3 15 15 1.5 180
Total per day 131 1,294 32.1 1,310
1
2
C. Example 3
Nutrient Intakes from Table 8-1, p 148, and nutrient contents from Table 8-2, p 148.
MET 150 mg/day
CYS1 2,500 mg (2.5 g)
Folate 1 mg
Protein 40 g
Energy 2,400 kcal
Fluid 2,400 mL
Betaine 8g
1

Hominex-2 93 g 0 837 27.9 381
1 2
L-Cystine 152 mL 0 1,520 0.0 0
Sugar 144 g (3/4 cup) 0 0 0.0 576
Food List Servings

Fats 4 8 0 0.4 200
Fruits 7 35 35 3.5 420
Free Foods A 7 7 7 1.4 350
Free Foods B 4 0 0 0.0 220
Total per day 150 2,495 40.0 2,407
1
2

A. Rationale
protein (46).
2. Well-nourished patients with homocystinuria respond to infection and trauma as do normal
persons.
3. Extent of protein catabolism determines subsequent elevation in blood MET concentration.
Jell-O ®; Polycose powder or liquid (Appendix 9, p A-9) or Pro-Phree (Appendix 11,
p A-10); and caffeine-free soft drinks (not diet drinks).
b. Add 1/3 cup Polycose powder may be added to liquid Pedialyte to yield 8 fl oz.
c. Return patient to Hominex medical food mixture and pre-illness diet as rapidly as
possible.
1) Begin with 1/2 original strength Hominex medical food mixture.

Homocystinuria
Age Nutrient
MET1,2 CYS2 Protein3,4 Energy3,4 Fluid5
Infants
0 to < 3 mo 15 - 30 300 3.50 - 3.00 120 (145 - 95) 150 - 125
3 to < 6 mo 10 - 25 250 3.50 - 3.00 115 (145 - 95) 160 - 130
6 to < 9 mo 10 - 25 200 3.00 - 2.50 110 (135 - 80) 145 - 125
9 to < 12 mo 10 - 20 200 3.00 - 2.50 105 (135 - 80) 135 - 120
(mg/kg) (mg/kg) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 10 - 20 100 - 200 > 30.0 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 8 - 16 100 - 200 > 35.0 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 6 - 12 100 - 200 > 40.0 2,400 (1650 -3300) 1,650 - 3,300
Women
11 to < 15 yr 6 - 14 50 - 150 > 50.0 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 6 - 12 25 - 125 > 55.0 2,100 (1200 - 3000) 1,200 - 3,000
> 19 yr 4 - 10 25 - 100 > 60.0 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 6 - 14 50 - 150 > 55.0 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 6 - 16 25 - 125 > 65.0 2,800 (2100 - 3900) 2,100 - 3,900
> 19 yr 6 - 15 25 - 100 > 70.0 2,900 (2000 - 3300) 2,000 - 3,300
1
Initiate prescription with lowest value for patient's age. Modify prescription based on frequently obtained plasma values
and growth in infants and children and frequently obtained plasma values and weight maintenance in adults.
2
From references 1, 14, 23.
3
From reference 15.
4
Based on ideal body weight in kilograms.
5
TABLE 8-2. Serving Lists For MET-Restricted Diets: Average Nutrient Content Per Serving1
Food List Nutrient

MET CYS Protein Energy
Fats 2 0 0.1 50
Fruits 5 5 0.5 60
2
Alimentum ® Protein-Hydrolysate Formula With Iron, Ready to Feed, 100 mL 54 32 1.86 68
Hominex®-1, powder, 100 g 0 450 15.00 480
Hominex®-2, powder, 100 g 0 900 30.00 410
Human Milk, 100 mL 2 22 20 1.05 72
Isomil Soy Formula With Iron, Ready to Feed, 100 mL 2 42 18 1.66 68
2
Similac With Iron Infant Formula, Ready to Feed, 100 mL 35 19 1.40 68
3
Whole cow's milk , 100 mL 86 31 3.39 63
1
From reference 14.
2
3

TABLE 8-3. Serving Lists for MET-Restricted Diets: Gerber ® Baby Foods (Beikost)
Food Weight Approximate MET CYS Protein Energy

BREADS AND CEREALS
Baked Finger Snacks

Animal crackers, cinnamon graham 24 6 crackers 19 45 1.4 107
Apple cinnamon cookies 20 2 cookies 24 40 1.6 85
Arrowroot cookies 18 3-2/3 cookies 24 53 1.5 82
Banana cookies 16 2 cookies 21 39 1.1 69
Pretzels 12 4 pretzels 24 47 1.5 47
Strawberry fruit bars 16 1-3/4 bar 20 32 0.9 65
Cereals, Dry
Barley 9 2 Tbsp + 1 tsp 20 31 1.1 34
Mixed 9 2 Tbsp + 1 tsp 19 28 0.9 35
Oatmeal 7 1 Tbsp + 2 tsp 20 40 1.1 28
Oatmeal/banana 12 3 Tbsp 20 35 1.4 48
Oateal/mixed fruit 10 2 Tbsp + 2 tsp 20 38 1.1 42
Rice 8 2 Tbsp 19 19 0.7 30
Rice/apple 12 3 Tbsp 20 20 0.7 47
Rice/apple bits 11 2 Tbsp + 2-3/4 tsp 20 20 0.8 43
Rice/banana 10 2 Tbsp + 2 tsp 21 23 0.7 39
Rice/mixed fruit 8 2 Tbsp 19 19 0.6 32
Cereals, Jarred
1st Foods ®
Oatmeal 57 1/4 cup 20 33 1.0 31
2nd & 3rd Foods ®
Banana/oatmeal/peach 106 7 1/2 Tbsp 20 28 1.2 78
Mixed/apples/bananas 100 7 Tbsp 20 36 1.2 76
Mixed/applesauce/banana 100 7 Tbsp 20 36 1.0 86
Oatmeal/apples/cinnamon 90 6 Tbsp + 1 tsp 20 38 1.0 60
Oatmeal/applesauce/banana 91 6 Tbsp + 1 tsp 20 38 1.2 76
Rice/applesauce/banana 80 5 Tbsp + 1-1/2 tsp 20 21 0.6 73
Vegetables
1st Foods ®
Peas 48 3 Tbsp + 1-1/2 tsp 20 18 1.4 24
Potatoes 133 9 Tbsp + 1 tsp 20 17 1.3 63
Creamed spinach 26 2 Tbsp 20 12 0.8 12
Garden vegetables 58 1/4 cup 20 18 1.2 22
Mixed vegetables 90 6 Tbsp + 1 tsp 20 18 1.2 32
Peas 52 3 Tbsp + 1-1/2 tsp 20 20 1.6 25
Sweet potatoes, 2nd Foods 96 6 Tbsp + 2 tsp 20 20 1.0 60
Sweet potatoes, 3rd Foods 84 7 Tbsp + 1 tsp 20 16 0.8 50
FRUITS/JUICES
Banana/pineapple 42 3 Tbsp 5 6 0.4 32

Banana/strawberry 42 3 Tbsp 5 7 0.4 39
Fruit salad 83 5 Tbsp + 2 tsp 5 7 0.3 52
Mixed fruit juice 100 3.2 fl oz 4 6 0.2 48
Orange juice 100 3.2 fl oz 7 4 0.6 42

Orange/banana/pineapple juice 50 1 1/5 fl oz 5 4 0.1 32
Pear juice 100 3.2 fl oz 5 4 0.2 48
Tropical blend 100 3.2 fl oz 5 5 0.6 56
1st Foods ®
Applesauce 86 1/4 cup + 2 Tbsp 5 2 0.2 48
Bananas 26 1 Tbsp + 2 tsp 5 5 0.3 26
Peaches 62 4 Tbsp + 2 tsp 5 6 0.4 27
Pears 62 4 Tbsp + 1 tsp 5 4 0.2 35
Prunes 100 7 Tbsp 5 5 1.0 101
2nd & 3rd Foods ®
Apple/blueberry 125 1/2 cup + 2 tsp 5 6 0.3 62
Apricot/mixed fruit 83 5 Tbsp + 2 tsp 5 7 0.5 50
Bananas 26 1 Tbsp + 2 tsp 5 5 0.3 23
Bananas/apples/pears 36 2 Tbsp + 1-1/2 tsp 5 6 0.3 30
Peaches 62 1/4 cup + 1 tsp 5 6 0.4 40
Pears 62 1/4 cup + 1 tsp 5 5 0.4 61
Pear/pineapple 62 1/4 cup + 1 tsp 5 4 0.2 34
Plums/apples 100 7 Tbsp 5 6 0.4 70
Prunes/apples 83 5 Tbsp + 2 tsp 5 7 0.5 64
Fruit Desserts
Guava 125 8 Tbsp + 2 tsp 5 3 0.4 88
Mango 100 7 Tbsp 5 3 0.4 74
Papaya 125 8 Tbsp + 2 tsp 5 3 0.4 80
Peach cobbler dessert, 2nd Foods 50 3 Tbsp + 1-1/2 tsp 5 3 0.2 38
Peach cobbler dessert, 3rd Foods 56 1/4 cup 5 5 0.3 43
Fruit Dices, Graduates™
Peaches 83 ND 5 7 0.4 41
Apple/carrot 167 5-1/3 fl oz 5 3 0.3 72
Apple/sweet potato 100 3-1/4 fl oz 5 5 0.3 52
White grape juice 100 3.2 fl oz 5 5 0.3 65
Tender Harvest ™
Pear/wild blueberry 167 11 Tbsp + 2 tsp 5 8 0.7 102
Tropical fruit blend 62 4 Tbsp + 1 tsp 5 5 0.4 46
Apple/sweet potato 125 8 Tbsp + 2 tsp 5 4 0.4 79
Pears/winter squash 31 2 Tbsp + 1-1/2 tsp 5 3 0.3 16
VEGETABLES
1st Foods ®
Carrots 100 7 Tbsp 10 10 0.9 35
Green beans 33 2 Tbsp + 1 tsp 10 8 0.4 10
Squash 59 1/4 cup 10 10 0.5 20
2nd Foods ®
Carrots 100 7 Tbsp 10 10 0.8 30
Green beans 50 3 Tbsp + 1-1/2 tsp 10 20 0.6 15
Squash 53 3 Tbsp + 2 tsp 10 11 0.4 17
3rd Foods ®
Carrots 56 1/4 cup 10 6 0.4 16
Green beans/rice 42 3 Tbsp 10 10 0.5 18
Squash 100 7 Tbsp 10 11 0.8 33

Tender Harvest ™
Butternut squash/corn 32 2 Tbsp + 3/4 tsp 10 6 0.6 16
Garden carrots/brown rice 83 5 Tbsp + 2 tsp 10 7 0.7 35
Green beans/potatoes 19 1 Tbsp + 1 tsp 10 5 0.4 12
Spring garden vegetables 59 4 Tbsp + 1 tsp 10 9 0.9 21
Vegetable Dices, Graduates™
Carrots 77 ND 10 6 0.5 18
Mixed vegetables 31 ND 10 9 0.6 14
FREE FOODS A
Fruit Dices
Apples 50 ND 1 2 0.1 24
Pears 33 ND 1 1 0.1 18
Fruit Juices
Apple/cranberry juice 100 3.2 fl oz 1 1 0.1 44
Apple/cherry juice 124 4 fl oz 1 1 0.3 62
Apple/grape juice 124 4 fl oz 1 1 0.1 64
Apple/prune juice 124 4 fl oz 1 1 0.1 32
Banana strawberry juice medley 100 3.2 fl oz 1 1 0.1 58
ND = no data.

Level Level
1 tsp = 1/3rd Tbsp = 4.8 g
1 Tbsp = 1/16th cup = 14.3 g
1/4 cup = 4 Tbsp = 57.2 g
1/3 cup = 5-1/3rd Tbsp = 76.2 g
1/2 cup = 8 Tbsp = 114.3 g
2/3 cup = 10 2/3rd Tbsp = 152.5 g
3/4 cup = 12 Tbsp = 171.5 g
1 cup = 16 Tbsp = 228.6 g

1, 2
TABLE 8-3. Serving Lists for MET-Restricted Diets: Table Foods

BREADS AND CEREALS
Cereals, Cooked. Level measure after cooking

Corn Grits
instant
cheese flavor 47 1/3 packet 22 21 0.9 36
plain 46 1/3 packet 17 16 0.7 27
regular, quick (plain) 60 1/4 cup 20 19 0.9 36
Cream of Rice ® 81 1/3 cup 21 12 0.7 42
Cream of Wheat ®
instant 60 1/4 cup 20 25 1.1 38
Mix'n Eat
plain 38 1/4 packet 17 21 0.9 34
quick 80 1/3 cup 22 27 1.2 43
regular 84 1/3 cup 23 28 1.3 45
Farina ® 60 1/4 cup 20 19 0.8 36
Maltex ® 47 3 Tbsp 20 24 1.1 34
Malt-o-Meal ® 80 1/3 cup 22 26 1.2 41
Oats, regular, quick, and instant 44 3 Tbsp 19 28 1.1 27
Ralston ® 47 3 Tbsp 20 23 1.0 25
Wheatena ® 51 3 Tbsp + 1 tsp 19 23 1.0 28
Whole Wheat Hot Natural 60 1/4 cup 20 33 1.2 38

All Bran ® 11 2 Tbsp 22 30 1.5 26
Alpha-Bits ® 14 1/2 cup 20 26 1.1 56
Apple Jacks ® 21 3/4 cup 22 26 1.1 82
100% Bran 12 3 Tbsp 21 30 1.5 32
Bran Buds ® 11 2 Tbsp 21 29 1.5 27
Bran Chex ® 9 3 Tbsp 18 20 1.0 30
40% Bran Flakes (Post ®) 12 1/4 cup 21 27 1.3 38
Cap'n Crunch ® 18 1/2 cup 21 22 1.0 78
Cheerios ® 7 1/3 cup 18 27 1.1 28
Cinnamon Toast Crunch ® 38 1 cup 22 26 1.3 60
Cocoa Krispies ® 12 1/3 cup 19 11 0.6 46
Cocoa Puffs ® 28 1 cup 19 19 1.0 110
Cookie Crisp ® 19 1/2 cup + 2 Tbsp 19 21 0.9 74
Corn Bran ® 13 1/4 cup + 2 Tbsp 20 21 0.9 74
Corn Chex ® 11 1/4 cup + 2 Tbsp 18 17 0.8 42
Corn Flakes ® 11 1/2 cup 22 21 0.9 44
Crispy Rice ® 9 1/3 cup 18 10 0.6 37
Crispy Wheat'n Raisins ® 19 1/4 cup + 3 Tbsp 20 25 1.3 65
C.W. Post ®
plain 12 2 Tbsp 21 26 1.1 54
w/ raisins 13 2 Tbsp 21 26 1.1 56
Froot Loops ® 18 1/2 cup + 2 Tbsp 21 24 1.1 69
Frosted Mini-Wheats ® 11 1-1/2 pieces 19 21 1.1 38
Frosted Rice Krinkles 14 7 Tbsp 20 12 0.7 55
Frosted Rice Krispies ® 14 1/2 cup 20 11 0.6 55
Fruit Wheat Squares 17 3 Tbsp + 1 tsp 19 23 1.2 59
Fruity Pebbles™ 16 1/2 cup 19 11 0.6 66

Golden Grahams ® 15 1/4 cup + 2 Tbsp 18 17 0.8 56
Grape Nut Flakes ® 10 1/3 cup 18 21 1.1 36
Honey Nut Cheerios ® 9 1/4 cup 18 25 1.0 36
Honey Nut Corn Flakes ® 19 1/2 cup 22 21 1.2 75
Honeycomb ® 16 3/4 cup 20 22 0.9 63
King Vitaman ® 16 3/4 cup 18 18 0.8 64
Kix ® 9 1/2 cup 18 19 0.8 37
Life ® 5 2 Tbsp 19 21 1.0 21
Lucky Charms ® 14 1/4 cup + 3 Tbsp 21 32 1.3 54
Nature Valley Granola ®, Toasted Oat Mixture 14 2 Tbsp 24 36 1.4 63
Nutri-Grain ®
barley 10 1/4 cup 19 26 1.1 38
corn 10 1/4 cup 20 20 0.8 40
rye 13 1/3 cup 20 33 1.2 48
wheat 15 1/3 cup 22 25 1.3 53
Oat Flakes 6 2 Tbsp 21 28 1.1 22
Product 19 ® 10 1/3 cup 22 22 1.0 39
Quisp ® 20 2/3 cup 22 23 1.0 83
Raisin Bran (Post ®) 14 1/4 cup 18 23 1.3 44
Rice Chex ® 13 1/2 cup 20 11 0.7 50
Rice, Puffed 10 3/4 cup 20 11 0.7 42
Special K ® 4 2 Tbsp 19 12 0.7 14
Sugar Frosted Flakes ® 18 1/2 cup 22 20 0.9 66
Sugar Pops ® 16 1/2 cup + 1 Tbsp 19 18 0.8 61
Sugar Smacks ® 17 1/4 cup + 3 Tbsp 20 23 1.2 62
Team ® 14 1/3 cup 22 18 0.9 55
Toasties ® 11 1/2 cup 22 20 0.9 44
Total ® 11 1/3 cup 19 21 1.1 39
Trix ® 14 1/2 cup 17 18 0.8 54
Wheat Chex ® 12 1/4 cup 20 23 1.1 42
Wheat
puffed 8 2/3 cup 21 23 1.2 29
shredded 12 1/2 large biscuit 22 25 1.3 42
Wheaties ® 11 1/4 cup + 2 Tbsp 18 20 1.0 38
Grains
Corn
cooked (cream style) 53 3 Tbsp + 1 tsp 19 8 0.9 38
meal 13 1 Tbsp + 1 tsp 21 23 1.0 46
on the cob (medium ear) 32 1/2 ear 21 8 1.0 29
Rice, prepared
brown 33 3 Tbsp 18 17 0.8 39
fried 28 2 Tbsp 18 14 0.7 36
pilaf 25 1 Tbsp + 2 tsp 19 20 1.0 38
Spanish 51 3 Tbsp + 1 tsp 19 16 0.9 44
white 39 3 Tbsp 18 15 0.8 42
instant 40 1 Tbsp + 2 tsp 20 17 0.9 43
Pasta, cooked
Macaroni 24 3 Tbsp 22 26 1.2 36
Noodles 30 3 Tbsp 21 24 1.2 37
Ramen ® Noodles 20 2 Tbsp 18 22 1.1 45
Spaghetti 21 2 Tbsp + 1 tsp 19 23 1.1 32

Tubers
Potatoes, sweet
baked, in skin (mashed) 50 1/4 cup 21 7 0.9 52
boiled, no skin (mashed) 41 2 Tbsp 17 5 0.7 43
canned, drained 98 1/2 cup 16 5 0.6 53
Potatoes, white
baked
no skin 61 1/2 cup 19 15 1.2 46
w/ skin 61 1/2 cup 22 18 1.4 66
boiled
no skin 78 1/2 cup 23 19 1.5 68
w/ skin 68 1/4 cup + 3 Tbsp 21 16 1.3 59
French fries, frozen (baked) (1/2" x 1/2" x 2") 50 10 pieces 20 12 1.8 163
hash browns, frozen (cooked) 52 1/3 cup 18 10 1.6 112
Yams, baked or boiled (mashed) 102 3/4 cup 21 18 1.5 71
Miscellaneous
Chow mein noodles 11 3 Tbsp 19 22 1.1 56
Croutons 8 1 Tbsp + 1/2 tsp 19 23 1.2 41
Flour
all purpose 11 1 Tbsp + 1-1/2 tsp 20 24 1.1 39
cake 14 3 Tbsp + 1 tsp 19 23 1.1 53
whole wheat 10 1 Tbsp + 1 tsp 22 29 1.3 33
Succotash 28 2 Tbsp + 1 tsp 19 15 1.4 32
Snack Foods
Breadsticks 9 1-1/2 breadsticks 19 23 1.1 35
Cookies
chocolate chip 24 2 cookies 19 22 1.3 124
fig bar 40 2-1/2 cookies 20 31 1.6 143
gingersnap 21 3 cookies 20 24 1.2 88
oatmeal raisin 14 1 cookie 19 20 0.9 64
Oreo ® 27 2-1/2 cookies 19 24 1.4 133
sugar butter 20 1-1/2 cookies 21 25 1.2 83
Sugar Wafer (Nabisco ®) 28 5 wafers 18 22 1.1 133
vanilla wafer 20 5 wafers 19 23 1.1 92
Crackers
graham (2" x 2") 14 2 crackers 20 24 1.1 54
Melba toast 9 1-1/2 pieces 20 24 1.2 31
Ritz ® 17 5 crackers 19 23 1.2 83
Ritz Bits ®, cheese 11 15 crackers 20 19 1.0 52
Rykrisp ® 11 1-3/4 pieces 20 23 1.1 39
saltine 12 4 crackers 19 23 1.1 52
Triscuits ® 14 3 crackers 20 24 1.2 63
Waverly ® 14 2 crackers 17 21 1.1 69
Ding Dongs ® 48 1 piece 20 24 1.4 219
Doodads, original 12 3 Tbsp + 1 tsp 19 22 1.3 58
Doritos ® 18 10 chips 19 22 1.3 88
Fritos ® 18 9 chips 20 18 1.2 98
Ho Ho's ® 28 1 piece 21 22 1.1 119
Marshmallow Puff 38 2 pieces 20 22 1.3 162

Popcorn
buttered 9 1 cup 22 20 0.9 41
caramel 13 1/4 cup + 2 Tbsp 19 18 0.8 50
plain 6 1 cup 18 17 0.8 23
Potato chips, regular (2" diameter) 20 10 chips 20 16 1.3 105
Pringles ® potato crisps 22 12 chips 19 15 1.2 124
Sno Balls ® 43 1 piece 22 22 1.3 149
Social Tea Biscuits ® 21 4 biscuits 21 24 1.2 96
Twinkies ® 32 3/4 piece 18 19 1.0 115
FATS
Butter, stick 10 2 tsp 2 0 0.1 72

Gravy, mushroom, canned 10 2 tsp 2 3 0.1 5
Margarine
liquid 5 1 tsp 2 1 0.1 34
soft 10 2 tsp 2 0 0.1 68
stick or brick 10 2 tsp 2 0 0.1 68
Nondairy creamer w/ sodium caseinate
liquid 5 1 tsp 2 0 0.1 7
powder 2 1 tsp 3 0 0.1 11
Rich's ® Coffee Rich 49 1-3/4 fl oz 2 2 0.1 74
Olives
green 9 2 large 2 1 0.1 11
black 9 2 large 1 1 0.1 17
French 11 2 tsp 2 1 0.1 47
Italian 11 2 tsp 2 1 0.1 51
ranch 5 1 tsp 3 2 0.1 26
Russian 5 1 tsp 2 1 0.1 25
Thousand Island 11 2 tsp 2 2 0.1 41
Cool Whip ®
extra creamy 5 1 Tbsp 3 1 0.1 16
regular 4 1 Tbsp 1 0 0.1 11
Dessert topping w/ sodium caseinate
frozen 4 1 Tbsp 2 0 0.1 13
pressurized 8 2 Tbsp 2 0 0.1 22
powder, amount to prepare 1 1 Tbsp 2 0 0.1 8
Richwhip ®
pressurized 28 1 fl oz 2 2 0.1 78
prewhipped 12 3 Tbsp 2 2 0.2 37
Whipped cream, pressurized 3 1 Tbsp 2 1 0.1 8
FRUITS
Apricots
canned, heavy syrup 129 1/2 cup halves 4 3 0.7 107
diced 78 1/2 cup 5 3 1.1 37
dried
cooked, diced 83 1/3 cup 5 3 1.1 70
halves 35 10 6 4 1.3 83

Avocados, all varieties, mashed 14 1 Tbsp 5 3 0.3 23
Bananas, sliced 42 3 Tbsp 5 7 0.4 39
1
Blackberries
canned, heavy syrup 32 2 Tbsp 6 5 0.4 32
raw 48 1/3 cup 5 4 0.3 25
1
Blueberries
raw 45 1/3 cup 5 3 0.3 25
1
Boysenberries
frozen, unsweetened 33 1/4 cup 5 4 0.4 16
1
Cherries
sour, red, canned, heavy syrup 77 1/3 cup 5 3 0.6 70
sweet
frozen, sweetened 48 3 Tbsp 5 3 0.6 44
raw 48 1/3 cup 5 3 0.6 34
Dates 25 3 fruits 6 11 0.5 68
Figs
dried
cooked 65 1/2 + 2 Tbsp 7 14 0.8 70
uncooked 19 1 fruit 5 9 0.6 48
whole, medium 75 1-1/2 fruits 5 9 0.6 56
Gooseberries, canned, light syrup 47 3 Tbsp 5 3 0.3 34
Grapefruit
canned or raw, sections 230 1 cup 5 5 1.3 69
Grapes
adherent skin 30 3 Tbsp 7 3 0.2 21
Thompson, seedless, canned, heavy syrup 31 2 Tbsp 5 2 0.2 23
slipskin 23 1/4 cup 5 2 0.1 14
Guava
raw, diced 110 2/3 cup 6 3 0.9 56
sauce 238 1 cup 5 3 0.8 87
Kiwi fruit 19 1/4 piece 5 2 0.2 12
Mangoes, diced 110 2/3 cup 6 3 0.6 72
3
Melons , cubed
cantaloupe 40 1/4 cup 5 4 0.4 14
casaba 42 1/4 cup 5 5 0.4 11
honeydew 85 1/2 cup 5 5 0.4 30
3
Nectarines , sliced 26 3 Tbsp 6 2 0.2 13
Oranges, all varieties
juice
fresh 248 8 fl oz 7 12 1.7 111
canned 249 8 fl oz 7 10 1.5 104
sections 22 2 Tbsp 5 2 0.2 11

Papayas, diced 140 1 cup 3 1 0.9 54
Peaches
canned, heavy syrup, sliced 64 1/4 cup 7 2 0.3 48
frozen, sweetened, sliced 47 3 Tbsp 7 2 0.3 44
sliced 42 1/4 cup 7 2 0.3 18
spiced, canned, heavy syrup 60 1/4 cup 6 2 0.2 45
Pears
canned, heavy syrup, halves 255 1 cup 5 5 0.5 188
dried
cooked, diced 64 1/4 cup 7 6 0.6 81
uncooked halves 18 1 4 3 0.3 46
sliced 124 3/4 cup 6 5 0.5 73
Persimmons, Japanese, raw 126 3/4 fruit 6 16 0.7 88
Pineapple
canned, heavy syrup, chunks or crushed 64 1/4 cup 6 1 0.2 50
diced 39 1/4 cup 4 1 0.2 19
juice
canned 62 2 fl oz 6 1 0.2 35
Plantain, cooked, sliced 51 1/3 cup 5 6 0.4 60
Plums
purple, canned, heavy syrup 129 1/2 cup 4 3 0.5 115
sliced 82 1/2 cup 5 4 0.6 46
Prunes
dried
cooked 53 1/4 cup 5 3 0.6 57
uncooked 25 3 fruits 5 3 0.7 60
Raisins, seedless 5 1-1/2 tsp 5 2 0.1 14
1
Raspberries
raw 41 1/3 cup 5 4 0.4 20
1
Rhubarb , cooked, sweetened 120 1/2 cup 7 6 0.5 139
Tangerines
canned, light syrup 47 3 Tbsp 6 3 0.3 17
juice
canned 249 8 fl oz 5 10 1.2 125
fresh 247 8 fl oz 5 10 1.2 106
sections 37 3 Tbsp 5 3 0.2 16
Watermelon, diced 80 1/2 cup 5 2 0.5 25
VEGETABLES
Vegetables are raw unless otherwise noted. Weight of raw vegetables is only for parts that can be eaten. Drain canned, cooked, and frozen
fruits before measuring or weighing.
Asparagus, cooked 45 1/2 cup 11 14 1.2 11

Bamboo shoots, cooked 60 1/2 cup 10 8 0.9 7
Beans
snap, green, cooked 41 1/3 cup 10 7 0.8 14
sprouts, mung (seed attached to sprout) 26 1/4 cup 9 4 0.8 8
yellow wax, cooked 65 1/4 cup 9 7 0.7 13

Beets, cooked
greens, chopped 48 1/3 cup 10 11 1.2 13
root 85 1/2 cup 10 11 0.9 26
Broccoli, fresh or frozen, cooked 24 2 Tbsp + 1-1/2 tsp 9 5 0.7 7
Brussels sprouts, fresh or frozen, cooked 42 2 sprouts 10 7 1.1 16
Cabbage, shredded
Chinese (Pak-choi)
cooked, 112 2/3 cup 10 19 1.8 13
raw 116 1-2/3 cup 11 20 1.7 15
red
cooked 94 10 Tbsp 10 9 1.0 20
raw 70 1 cup 10 8 1.0 19
white
coleslaw 60 1/2 cup 11 9 0.8 41
cooked 112 3/4 cup 11 9 1.1 24
Carrots
cooked 137 3/4 cup + 2 Tbsp 10 12 1.5 61
raw, shredded 137 1-1/4 cups 10 11 1.4 59
Cauliflower
cooked 41 1/3 cup 11 9 0.8 10
raw 33 1/3 cup 9 8 0.7 8
Celery, diced
cooked 225 1-1/2 cups 9 7 1.1 34
raw 180 1-1/2 cups 9 7 1.2 29
Chives 36 3/4 cup 11 18 1.0 9
Collards, cooked, chopped 63 1/3 cup 9 7 0.7 9
Cucumbers, pared, sliced 208 2 cups 8 6 1.1 27
Eggplant, cubed
cooked 120 1-1/4 cups 11 5 1.0 34
raw 82 1 cup 10 5 0.9 21
Endive, shredded 75 1-1/2 cups 11 8 0.9 13
Kale, cooked 49 1/4 cup + 2 Tbsp 9 12 0.9 16
Kohlrabi, cooked, sliced 72 1/4 cup + 3 Tbsp 10 5 1.3 21
Leeks, diced
cooked 91 3/4 cup + 2 Tbsp 9 13 0.7 28
raw 52 1/2 cup 9 13 0.8 32
Lettuce, shredded
bibb 56 1 cup 9 8 0.7 7
iceberg 70 1-1/4 cups 10 10 0.7 9
leaf 56 1 cup 9 9 0.7 10
Romaine 49 3/4 cup + 2 Tbsp 10 9 0.8 8
Mushroom, Agaricus bisporus, sliced
cooked 26 1/3 cup 10 1 0.5 6
raw 22 1/3 cup 9 1 0.5 6
Mustard greens, chopped
cooked 46 1/3 cup 10 16 1.0 7
raw 42 3/4 cup 11 17 1.1 11
Okra, cooked 53 1/3 cup 11 10 1.0 17
Onions
cooked 158 3/4 cup 11 25 1.4 44
diced 106 2/3 cup 11 22 1.2 36
rings 13 1-1/4 rings 10 14 0.7 51
Parsnips, cooked 59 1/4 cup + 2 Tbsp 10 4 0.8 47
Peas, green
cooked 13 1 Tbsp + 1 tsp 11 4 0.7 11

pods (edible)
cooked 80 1/2 cup 10 30 2.6 34
raw 95 2/3 cup 11 31 2.7 40
w/ carrots, cooked 20 2 Tbsp 9 4 0.6 10
Pickles, cucumber
dill
relish 19 1 Tbsp + 1 tsp 10 1 0.1 4
whole 180 3 pickles 9 7 1.3 20
sweet
relish 251 1 cup 10 8 1.3 346
sliced 180 6 pickles 9 7 1.3 263
Pumpkin
cooked 81 1/3 cup 10 2 0.9 28
pie mix (no eggs) 89 1/3 cup 11 3 1.0 93
Radishes, red, sliced 145 1-1/4 cup 10 7 0.9 25
Rutabagas
raw, cubed 105 3/4 cup 11 12 1.3 38
Sauerkraut 118 1/2 cup 11 9 1.1 22
Shallots, chopped 40 1/4 cup 11 22 1.0 29
Spinach, chopped
cooked 19 1 Tbsp + 2 tsp 10 6 0.5 4
raw 18 1/3 cup 10 7 0.5 4
summer, all varieties
cooked 67 1/4 cup + 2 Tbsp 9 7 0.6 13
sliced 65 1/2 cup 11 8 0.8 13
winter
acorn, baked 68 1/3 cup 10 7 0.8 38
butternut, baked 103 1/2 cup 11 8 0.9 41
Hubbard, baked 58 1/2 cup 10 8 1.4 29
spaghetti, boiled 135 3/4 cup + 2 Tbsp 9 7 0.9 39
Tomatoes
catsup 16 1 Tbsp 11 3 0.3 16
juice 128 4 fl oz 10 15 1.2 33
paste 66 1/4 cup 12 15 2.5 55
purée 49 3 Tbsp 9 11 1.9 41
raw, diced 125 1/2 cup 11 13 2.1 51
sauce 122 1/2 cup 9 10 1.6 37
spaghetti sauce, no meat 124 1/2 cup 11 14 2.3 135
stewed, canned 135 3/4 cup 11 16 1.2 26
Turnips
greens, cooked
chopped 36 1/4 cup 9 5 0.4 7
w/ turnips 24 2 Tbsp + 1 tsp 10 5 0.5 4
root
cooked 117 3/4 cup 11 5 0.8 21
diced 98 3/4 cup 11 5 0.9 26
Vegetables, mixed, cooked 28 2 Tbsp + 1-1/2 tsp 10 7 0.8 17
Soups, Campbell's ®, Condensed. Weigh or measure before diluting and dilute with water only.
Asparagus, Cream of 31 2 Tbsp 10 8 0.6 22
Beef Broth 15 1 Tbsp 9 4 0.3 2
Celery, Cream of 39 2 Tbsp + 1-1/2 tsp 9 6 0.5 28
Chicken
Cream of 16 1 Tbsp 10 6 0.4 15
Gumbo 31 2 Tbsp 11 4 0.7 14

Noodle 15 1 Tbsp 9 6 0.5 9
Vegetable 20 1 Tbsp + 1 tsp 10 4 0.6 13
Minestrone 31 2 Tbsp 11 8 1.1 21
Mushroom, Cream of 31 2 Tbsp 10 6 0.5 32
Onion 38 2 Tbsp + 1-1/2 tsp 9 21 1.2 18
Potato, Cream of 39 2 Tbsp + 1-1/2 tsp 9 9 0.5 23
Scotch Broth 15 1 Tbsp 11 4 0.6 10
Tomato 63 1/4 cup 11 14 1.0 43
Tomato Bisque 39 2 Tbsp + 1-1/2 tsp 9 7 0.7 38
Vegetable, Chunky, Ready To Serve 90 1/4 cup + 2 Tbsp 10 10 1.3 46
Vegetable, Old Fashioned 46 3 Tbsp 9 9 0.8 24
Vegetarian Vegetable 46 3 Tbsp 9 9 0.8 27
FREE FOODS A
Desserts
Apple butter 20 1 Tbsp 1 1 0.1 37
Fruit ices 12 1 Tbsp 1 1 0.0 16
Fruit juice bars 14 1 bar 1 1 0.2 55
Fun Fruits 16 1 Tbsp 2 2 0.2 65
Gelatin dessert, prepared 11 1/4 cup 1 0 0.1 8
M&M ® plain candy 1 1 piece 1 1 0.1 4
Marshmallow, large 8 1 1 0 0.2 26
Mocha Mix, frozen vanilla 8 1 Tbsp 1 2 0.1 17
Fruits/Juices
Apples
canned w/ sugar 67 1/3 cup 1 1 0.1 45
dried, diced
cooked 64 1/4 cup 1 2 0.1 36
uncooked 11 2 Tbsp 1 1 0.1 26
whole 69 1/2 fruit 1 2 0.1 41
Applesauce w/ sugar 64 1/4 cup 1 1 0.1 48
Cranberry sauce w/ sugar 35 2 Tbsp 1 1 0.1 52
Lemon juice 31 1 fl oz 1 1 0.1 6
Lime juice 92 3 fl oz 1 2 0.2 19
Marmalade 13 2 tsp 1 1 0.1 33
Pie filling
apple 81 1/3 cup 1 2 0.1 89
cherry 26 1 Tbsp + 2 tsp 1 1 0.1 27
peach 17 1 Tbsp 1 1 0.1 18
strawberry 83 1/3 cup 1 3 0.4 90
Papaya nectar 94 3 fl oz 1 1 0.2 54
Pear nectar 94 3 fl oz 1 1 0.1 56
Tangerine juice w/ sugar 62 2 fl oz 1 3 0.3 31
Miscellaneous
Chocolate drink powder (Quik ®) 3 1 tsp 1 1 0.1 11
FREE FOODS B
These foods contain little or no MET or CYS. They may be used as desired if patient is not overweight and if they do not depress appetite for
prescribed foods.
Beverages

Carbonated beverages
cola 123 4 fl oz 0 0 0.0 50
cream soda 124 4 fl oz 0 0 0.0 63
Dr Pepper ® 123 4 fl oz 0 0 0.0 50
ginger ale 122 4 fl oz 0 0 0.0 41
grape soda 124 4 fl oz 0 0 0.0 53
lemon lime soda 123 4 fl oz 0 0 0.0 49
orange soda 124 4 fl oz 0 0 0.0 60
root beer 123 4 fl oz 0 0 0.0 50
Fruit Drink (Hi-C ®) 124 4 fl oz 0 0 0.0 58
Gatorade ® Thirst Quencher 121 4 fl oz 0 0 0.0 30
Kool-Aid ® sweetened w/ sugar 123 4 fl oz 0 0 0.0 49
Lemonade sweetemed w/ sugar 123 4 fl oz 0 0 0.1 49
Orange drink powder (Tang ®) 12 1 Tbsp 0 0 0.0 47
Strawberry Quik ® drink powder 8 1 Tbsp 0 0 0.0 33
Desserts/Sweets
Candies
candy corn 16 10 pieces 0 0 0.0 58
gumdrops 16 8 pieces 0 0 0.0 56
hard candy 15 3 pieces 0 0 0.0 58
jelly beans 14 5 pieces 0 0 0.0 51
Fruit bars, frozen
raspberry 74 1 bar 0 4 0.6 60
strawberry 74 1 bar 0 0 0.0 60
Jams/preserves 20 1 Tbsp 0 1 0.1 54
Jelly 20 1 Tbsp 0 0 0.0 54
Lemon pudding, canned (Hunt's ®) 121 1 can 0 0 0.0 151
Popsicle ®, twin 128 1 popsicle 0 0 0.0 95
Sugar
brown 14 1 Tbsp 0 0 0.0 52
table 12 1 Tbsp 0 0 0.0 48
Syrup
corn 20 1 Tbsp 0 0 0.0 58
maple 20 1 Tbsp 0 0 0.0 50
table 20 1 Tbsp 0 0 0.0 50
Miscellaneous
Oil
olive 13 1 Tbsp 0 0 0.0 119
vegetable 14 1 Tbsp 0 0 0.0 120
Richwhip ® liquid 14 1 Tbsp 0 0 0.0 40
Vinegar/oil salad dressing 16 1 Tbsp 0 0 0.0 70
1
MET calculated as 1.4% of protein and CYS as 1.2% of protein.
2
See Appendix 12, p A-11, for nutrient composition of very-low-protein foods.

TABLE 8-4. Nutrient Composition of HOMINEX ®-1 1,3 and HOMINEX ®-2 2,3
4
Nutrient Hominex-1 Hominex-2
Energy, kcal 480 32 410 13.7
Protein equiv, g 15.00 1.000 30.00 1.000
Nitrogen, g 2.40 0.160 4.80 0.160
Amino acids, g 17.67 1.178 35.34 1.178
Cystine, g 0.45 0.030 0.90 0.030
Histidine, g 0.42 0.028 0.84 0.028
Isoleucine, g 1.08 0.072 2.16 0.072
Leucine, g 1.68 0.112 3.36 0.112
Lysine, g 1.00 0.067 2.00 0.067
Methionine, g trace 0 trace 0
Phenylalanine, g 0.88 0.059 1.76 0.059
Threonine, g 0.70 0.047 1.40 0.047
Tryptophan, g 0.17 0.011 0.34 0.011
Tyrosine, g 0.89 0.059 1.78 0.059
Valine, g 1.22 0.081 2.44 0.081
Carnitine, mg 20 1.33 40 1.33
Taurine, mg 40 2.67 50 1.67
Carbohydrate, g 53.0 3.53 35 1.17
Fat, g 21.7 1.45 14 0.47
4 5
Linoleic acid, g 2.00 0.133 1.50 0.050
6 7
0.36 0.024 0.17 0.006
Minerals
Calcium, mg 575 38 880 29
Chloride, mg/mEq 435/12.27 29.0/0.82 1,160/32.72 38.7/1.09
Chromium, µg 11 0.73 27 0.90
Copper, mg 1.10 0.073 1.00 0.033
Iodine, µg 65 4.33 100 3.33
Iron, mg 9.0 0.60 13 0.43
Magnesium, mg 50 3.33 225 7.50
Manganese, mg 0.50 0.033 0.80 0.027
Potassium, mg/mEq 675/17.26 45./1.15 1,370/35.04 45.7/1.17
Selenium, µg 20 1.33 35 1.17
Sodium, mg/mEq 190/8.26 12.7/0.55 880/38.28 29.3/1.28
Zinc, mg 8.0 0.53 13 0.43
Vitamins
A, µg RE 420 28 660 22
D, µg 7.50 0.50 7.50 0.25
E, mg α-TE 10.10 0.67 12.10 0.40
K, µg 50 3.33 60 2.00
Biotin, µg 65 4.33 100 3.33
B6, mg 0.75 0.050 1.30 0.043
B12, µg 4.90 0.327 5.00 0.167
Choline, mg 80 5.33 100 3.33
Folate, µg 230 15 450 15
Inositol, mg 40 2.67 70 2.33
Niacin equiv, mg 12.80 0.850 21.7 0.72
Riboflavin, mg 0.90 0.060 1.80 0.060
Thiamin, mg 1.90 0.127 3.25 0.108
1 2
3
Approximate packed weight of Hominex in level, dry US standard household measures:
Hominex-1 Hominex-2
1 Tbsp = 7g 8g
1/4 cup = 26 g 32 g
1/3 cup = 35 g 41 g
1/2 cup = 53 g 61 g
1 cup = 105 g 117 g
4 5
6 7

TABLE 8-5. Homocystinuria Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

1 1 2
Length/ Weight Head MET CYS Homo- Hgb Hct Ferritin Transthyretin Folate MET CYS Protein Energy
1
Height Circum cystine
(mo/d/yr) (yrs/mo) (cm) (kg) (cm) (g/dL) (%) (ng/mL) (mg/dL) (ng/mL) (mg) (mg) (g) (kcal)
Homocystinuria 163
1
2
Indicate if serum or erythrocyte.
REFERENCES
1985, 115-135.
2. Acosta PB: Growth, tolerance, plasma amino acids, and plasma biochemistries of infants with cystathionine-ß-
synthase deficiency (B-6 nonresponsive) or phenylalanine hydroxylase deficiency. Columbus OH: Ross
Laboratories, 1992.
3. Acosta PB, Yannicelli S: Nutrition support of inherited disorders of amino acid metabolism. Part 2. Top Clin Nut
1995;10:48-72 (Review).
5. Albin RL, Albers JW, Greenberg HS, et al: Acute sensory neuropathy-neuronopathy from pyridoxine overdose.
Neurology 1987;37:1729-1732.
Dis 2000;23 (Suppl 1):29A.
7. Berardelli A, Thompson PD, Zaccaqnini M, et al: Two sisters with generalized dystonia associated with
homocystinuria. Mov Disord 1991;6:163-165.
8. Berg WVd, Verbrook FD, Bos PJM: Homocystinuria presenting as longstanding thromboembolic disease. Br J
Ophthalmol 1990;74:696-697.
9. Behrman RE, Kliegman RM, Arvin AA: Nelson Textbook of Pediatrics, ed 15. Philadelphia: WB Saunders Co,
1996.
11. Carey MC, Fennelly JJ, Fitzgerald O: Homocystinuria II. Subnormal serum folate levels, increased folate clearance
and effects of folic acid therapy. Am J Med 1968;45:26-31.
12. Celermayer DS, Sorensen, K, Ryalls M, et al: Impaired endothelial function occurs in the systemic arteries of
children with homozygous homocystinuria but not in their heterozygous parents. J Am Coll Cardiol
1993;22:854-858.
13. Dudman NPB, Wilcken DEL: Increased plasma copper in patients with homocystinuria due to
cystathionine-ß-synthase deficiency. Clin Chim Acta 1983;127:105-113.
18. Herbert VD, Das KC: Folic acid. In Shils ME, et al (eds): Modern Nutrition in Health and Disease, ed 9.
Philadelphia: Williams & Wilkins, 1999, pp 433-448.
20. Ilan Y, Eid A, Rivkind AI, et al: Gastrointestinal involvement in homocystinuria. J Gastroent Hepat 1993;8:60-62.
21. Kempster PA, Brenton DP, Gale AN, Stern GM: Dystonia in homocystinuria. J Neurol Neurosurg Psychiatry
1988;51:859-862.
1982.
1987;1:1-17.
26. Mpofu C, Whitehouse C, Fowler B, Wraith JE: No sensory neuropathy during pyridoxine treatment in
homocystinuria. Arch Dis Child 1991;66:1081-1082.
27. Mudd SH, Levy HL, Kraus J: Disorders of transsulfuration. In Scriver CR, et al (eds): The Metabolic and Molecular
Bases of Inherited Metabolic Disease, ed 8. New York: McGraw-Hill Medical Publishing Division, 2001,
pp 2007-2056.
28. Mudd SH, Skovby F, Levy H, et al: The natural history of homocystinuria due to cystathionine-ß-synthase
deficiency. Am J Hum Genet 1985;37:1-31.

29. Munnich A, Saudubray JM, Dautzenberg MD, et al: Diet-responsive proconvertin (factor VII) deficiency in
homocystinuria. J Pediatr 1983;102:730-734.
acidsand peptides in growing rats. J Pediatr Gastroenterol Nutr 1990;10:490-496.
31. Parrot F, Redonnet-Verhet I, Lacombe D, Gin H: Osteoporosis in late-diagnosed adult homocystinuric patients.
32. Patil RV, Kulthe SG, John Boby KF, et al: Chronic pancreatitis in homocystinuria. Indian Pediatr 1995;32:469-470.
1955;56:231-251.
35. Sansaricq C, Garg S, Norton PM, et al: Cystine deficiency during dietotherapy of homocystinemia. Acta Paediatr
Scand 1975;64:215-218.
36. Schaumburg H, Kaplan J, Windebank A, et al: Sensory neuropathy from pyridoxine abuse. N Engl J Med
1983;309:445-448.
38. Shoji Y, Takahashi T, Sato W, et al: Acute life-threatening event with rhabdomyolysis after starting on high-dose
pyridoxine therapy in an infant with homocystinuria. J Inher Metab Dis 1998;21:439-440.
39. Smith CA, Nelson NM: The Physiology of the Newborn Infant, ed 4. Springfield, Ill: Charles C Thomas Publisher,
1976.
1983;7:280-288.
42. Smolin LA, Benevenga NJ, Berlow S: The use of betaine for the treatment of homocystinuria. J Pediatr
1981;99:467-472.
Clin Nutr 1964;15:322-330.
1989;143:828-832.
45. Spooner RJ, Fell GS, Halls DJ, et al: Selenium depletion and its correction in a child with homocystinuria. Clin Nutr
1986;5:29-32.
1977;30:1269-1280.
47. Weir DG, Scott JM: Vitamin B12 "Cobalamin". In Shils ME, et al (eds): Modern Nutrition in Health and Disease,
ed 9. Philadelphia: Williams & Wilkins, 1999, pp 447-458.
48. Wilcken DEL, Wilcken B, Dudman NPB, et al: Homocystinuria — The effects of betaine in the treatment of patients
not responsive to pyridoxine. N Engl J Med 1983;309:448-453.
49. Yap S, Naughten E: Homocystinuria due to cystathionine ß-synthase deficiency in Ireland: 25 years’ experience of
a newborn screened and treated population with reference to clinical outcome and biochemical control. J Inher
Metab Dis 1998;21:738-747.
50. Yoshida Y, Nakano A, Hamada R, et al: Patients with homocystinuria: High metal concentrations in hair, blood
and urine. Acta Neurol Scand 1992;86:490-495.

PROTOCOL 9 — Glutaric Aciduria Type I or 2-Ketoadipic Aciduria

GLUTAREX ®-1 and GLUTAREX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
A. Glutaric Aciduria
Glutaric aciduria type I (GA-I) is an autosomal recessive disorder caused by a defect in activity of
glutaryl-CoA dehydrogenase (GDH) (Figure H), a mitochondrial flavin-dependent enzyme required
for catabolism of essential lysine (LYS) and tryptophan (TRP) (24, 32). A defect in GDH results in
accumulation of glutaric acid, 3-hydroxy (OH)-glutaric and glutaconic acids in physiologic fluids.
Pharmacologic doses of oral riboflavin (100-200 mg/day), a coenzyme for the GDH complex, are
given to increase half-life of any residual enzyme.
GA-I is heterogeneous in its clinical and biochemical presentations (24, 26, 31). Patients
with GA-I appear normal at birth and develop normally until a viral-like illness results in
overwhelming clinical crisis and neurologic deterioration. Symptoms often include macrocephaly,
myoclonic seizures, ataxia, choreoathetosis, episodic vomiting, intermittent metabolic acidosis or
a Reye-like syndrome (5, 24, 29, 30). Neuro-imaging shows characteristic frontotemporal atrophy
and delayed myelination (2, 5, 7). Plasma glutaric acid concentrations during acute crises vary
and may even be normal (5, 29). Abnormal urinary organic acids and acylcarnitine concentration
is diagnostic in most cases (29, 31, 42). Nearly 100 mutations have been identified in the gene
encoding GDH. No clear correlation has been found between genotype and clinical phenotype
(31).
The exact cause of the pathophysiology of GA-I is not known, but may be due to toxic
effects of glutaric acid, quinolinic acid, or 3-OH-glutaric acid (24, 28, 67) or an abnormality in
γ−aminobutyric acid metabolism (24). Incidence of GA-I is not known, but may be as high as one
in 30,000 live births (35) with an increased prevalence in an old-order Amish community (43).
Figure H. Lysine and tryptophan metabolism in 2-ketoadipic aciduria and glutaric aciduria type I
B. 2-Ketoadipic Aciduria
2-Ketoadipic aciduria (KAA) results from defect in activity of 2-ketoadipic acid dehydrogenase
(KAD), which is required for metabolism of essential LYS and TRP. Defect in KAD results in
168 Glutaric Aciduria Type I or 2-Ketoadipic Aciduria © 2001 Ross Products Division
accumulation of plasma LYS and TRP and 2-aminoadipic, 2-ketoadipic, and 2-OH-adipic acids in
biologic fluids. Symptoms include hypotonia, intermittent metabolic acidosis, and motor and
© 2001 Ross Products Division Glutaric Aciduria Type I or 2-Ketoadipic Aciduria 169
developmental delay (50). One patient has been described with psychomotor retardation and
seizures with abnormal electroencephalograms (15). Actual incidence of KAA is not known, and
few patients have been reported.
No clear correlation has been found between the metabolic defect and clinical symptoms
in patients with KAA (24, 50). Large phenotypic heterogeneity in this disorder and findings of
asymptomatic patients suggest that KAA may be a benign defect (45). However, one patient
showed clinical improvement after diet intervention (24).

Early identification and appropriate medical and nutrition management of patients with GA-I during
acute crises affect outcome. Researchers have reported near-normal development in most patients
treated prior to initial neurologic crises (5, 31, 42, 68). Patients who are diagnosed after acute
encephalopathy suffer permanent loss in motor skills, but preserve cognitive functions. In
neurologically impaired patients, treatment results in limited or no clinical improvement, but may
prevent further neurologic deterioration. Treatment should be directed towards normalization of
plasma glutaric acid, and maintaining low normal LYS and TRP concentrations.

A. The Defects
1. GA-I results from defect in GDH.
2. KAA results from defect in KAD.
B. Screening
1. Neonatal screening for the presence of elevated plasma glutarylcarnitine concentrations using
tandem mass spectrometry can be used to identify patients with GA-I.
C. Clinical Evaluation
1. Glutaric aciduria type I.
a. Diagnostic studies should be conducted in any child who has following signs within first
18 months of life (24, 29):
1) Macrocephaly (5, 30).
2) Abnormal CT scan or magnetic resonance imaging (MRI) (5, 7, 24).
3) Abnormal movement disorder including spasticity and choreoathetosis.
4) Ketosis, vomiting, hepatomegaly, coma, and convulsions.
5) Metabolic acidosis.
6) Hypoglycemia (14).
7) Renal cysts.
2. 2-Ketoadipic aciduria.
a. Diagnostic studies should be conducted in any child who has following signs within first
2 years of life (24).
1) Hypotonia.
2) Motor and developmental delay (49, 50).
3) Psychomotor retardation and seizures (15).
4) Metabolic acidosis.

A. Correct Primary Imbalance in Metabolic Relationships (16)
1. Restrict dietary LYS and TRP to amounts tolerated by patient to maintain treatment plasma
concentrations.
1. Administer trial of pharmacologic oral riboflavin if any GDH activity is present (29).
V. Nutrition Support During Acute Illness

B. Medical Care
1. Implement standard medical management.
2. Intravenous L-carnitine (100 to 300 mg/kg), glucose infusion, and bicarbonate therapy have
been suggested to treat acute crises (5, 29).
C. Patients With Acute Metabolic Acidosis and Neurologic Depression
1. Begin oral or nasogastric feeds free of LYS and TRP with sufficient protein and energy to
promote anabolism.
a. Provide recommended protein (Table 9-1, p 176) with Glutarex (Table 9-2, p 177).
b. Provide remaining prescribed energy with Pro-Phree ® Protein-Free Energy Module With
Iron, Vitamins & Minerals (Appendix 11, p A-10) or Polycose® Glucose Polymers
(3.8 kcal/g) (Appendix 9, p A-9).
c. When plasma concentrations of LYS and TRP approach lower limit of normal and urine
contains no glutaric, 3-OH-glutaric, glutaconic, 2-ketoadipic, 2-hydroxyadipic, or
2-aminoadipic acids, begin adding LYS and TRP using Similac ® With Iron Infant
Formula, beikost, or table foods (Table 9-3, p 178).
Note: Some patients do not excrete glutaric acid during acute crises (5, 24, 29).
2. L-carnitine therapy is essential during acute illness. Administration should be considered if
insufficient Glutarex is provided to supply prescribed oral carnitine.
a. Recommended L-carnitine intake is between 100 and 300 mg/kg (Appendix 26, p A-28).
4. See references 5 and 42 for more information on treatment during acute intermittent illness.

A. Plasma LYS and TRP Concentrations
1. Maintain 2- to 4-hour postprandial plasma LYS and TRP concentrations in low-normal ranges
given below, or on low side of normal for age in laboratory used.
a. LYS: 45-90 µmol/L (38, 41).
b. TRP: 15-65 µmol/L (3).
c. In practice, obtaining blood 2 to 4 hours postprandially is not always possible. Acceptable
(Practical Aspects of Nutrition Support, p viii).
B. Plasma Glutaric Acid Concentration
1. Maintain plasma concentration of glutaric acid < 250 ng/mL.
2. See Table 9-4, p 178, for laboratory that quantifies plasma glutaric acid.
C. Urine Metabolites
1. Maintain normal excretion of glutaric, 3-HO-glutaric, glutaconic, 2-ketoadipic, or
2-hydroxyadipic acids. Organic acids may not be present in urine even during acute illness (9,
10, 24, 29).
D. Growth, Development, and Nutrition Status
in adults.
a. Avoid prolonged fasting.
4. Maintain adequate hydration.
5. Prevent catabolism and neurologic deterioration.
E. Plasma Free Carnitine Concentration
1. Maintain normal plasma free carnitine concentration (≥ 30 µmol/L).

A. LYS and TRP
1. Prescribe LYS and TRP intakes that promote goals of long-term nutrition support (Table 9-1,
p 176).
2. LYS and TRP requirements.
a. Are not well-established because of limited clinical experience with these disorders.
b. Vary based on genotype and enzyme activity, which ranges from 0% to 10% of normal
(24, 32) in GA-I.
c. Vary in same patient, depending on:
1) Age.
2) Growth rate.
4) State of health.
3. Lowest values for age for LYS and TRP (Table 9-1, p 176) are suggested for initiating long-
term nutrition support.
4. Changing requirements of patients are determined by frequent monitoring of plasma LYS,
TRP, and glutaric acid concentrations and growth in infants and children, and plasma LYS,
TRP, and glutaric acid concentrations and weight in adults.
a. See Section X, Suggested Evaluation of Nutrition Support, p 172.
Warning: LYS and TRP deficiencies result in the following adverse effects:
LYS (60): Impaired weight gain and excessive urinary nitrogen excretion.
TRP: Impaired weight gain; increased plasma urea nitrogen; increased
plasma α-amino nitrogen; decreased plasma cholesterol concentration
(59), irritability, sleeplessness, and anorexia (5).
B. Protein
(Table 9-1, p 176).
c. Rapid catabolism of amino acids (27, 34, 57).
concentrations, osteopenia, hair loss, and decreased LYS and TRP tolerance.
C. Energy
3. Choreoathetosis, seizures, and intermittent febrile illness (5, 24, 31) may significantly increase
energy needs.
Warning: Inadequate energy intake may precipitate metabolic and neurologic crises;
failure to thrive in infants and weight loss in children and adults and
decreased LYS and TRP tolerance.
D. Fluid
2. Requirements may be higher than recommended secondary to accompanying fever,
excessive perspiration, or presence of choreoathetosis or seizures (24, 29).
E. Oral L-Carnitine (29, 54, 62)
1. Prescribe amount that maintains normal plasma free carnitine concentrations.
2. The usual dose is 100 mg/kg/day during long-term care (29, 62).
a. Excessive carnitine may cause gastrointestinal distress and fishy odor.
F. Riboflavin (GA-I only)
1. A small percentage of patients may respond to pharmacologic doses of riboflavin (10).
2. Prescribe a trial of 100 mg oral riboflavin daily (5).
G. Preformed Niacin
1. Restriction of TRP intake may require administration of 100% of RDA for age for niacin
equivalents (Appendices 13 and 14, pp A-14 and A-15), since restricted TRP may be
inadequate for de novo niacin synthesis.

A. LYS
(Table 9-3, p 178) required to fill LYS prescription.
a. Low-iron infant formula, whole cow's milk, or evaporated milk should not be used as LYS
2. Measure liquid infant formula and whole cow's milk with disposable syringe or graduated
cylinder. Weigh powdered infant formula on scale that reads in grams.
3. Add beikost or table foods to gradually displace LYS provided by infant formula when infant is
3 to 4 months of age or is developmentally ready. This may not be possible with a
neurologically impaired patient.
specified amounts to fill diet plan.
B. TRP
1. Calculate approximate amount of TRP provided by infant formula with iron, beikost, whole
cow's milk, or table foods (Table 9-3, p 178) required to fill LYS prescription.
2. Subtract amount determined above from TRP prescription.
a. TRP provided by infant formula, beikost, whole cow's milk, or table foods will be close to
amount prescribed.
C. Protein
table foods (Table 9-3 p 178) required to fill LYS and TRP prescriptions.
3. Supply any remaining prescribed protein with Glutarex (Table 9-2, p 177).
a. Glutarex-1 is for infants and toddlers and Glutarex-2 is for children, adolescents, and
adults.
b. Weigh Glutarex powder on scale that reads in grams because of variability of household
c. See Table 9-2 (p 177, footnote 3) for approximate packed weight of Glutarex powder in
D. Energy
1. Calculate energy provided by Glutarex (Table 9-2, p 177) and infant formula with iron, beikost,
whole cow's milk, or table foods (Table 9-3, p 178) required to fill LYS and protein
prescriptions.
2. Subtract amount of energy supplied by these sources from total energy prescription.
3. Provide remaining prescribed energy with Polycose ® Glucose Polymers powder (23
kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9); Pro-Phree ® Protein-Free
E. L-Carnitine (Appendix 26, p A-28)
1. If L-carnitine in prescribed Glutarex is insufficient to maintain normal plasma concentration of
free carnitine, add oral L-carnitine to medical food mixture.
2. L-carnitine may also be added to beikost or table foods and fruit juices.
3. If not mixed with medical food mixture, administer TID or QID with meals.
4. L-carnitine tablets may be used if patient is old enough to swallow them.
F. Riboflavin (Appendix 26, p A-28)

1. Supplement with 100 mg oral riboflavin, administer 15-25 mg with each feed (73).
2. Do not give intravenously because of low solubility.
G. Fluid and Mixing Instructions

1. Add sufficient boiled, cooled water to infant formula, Glutarex, carbohydrate (if needed), and
L-carnitine (if needed) to yield prescribed volume. Tap water may replace boiled, cooled water
when preparing Glutarex for older infants, children, and adults.
stored medical food mixture prior to each feeding.
8. For children and adults, chill Glutarex medical food mixture to improve taste.
G. Diet Guide
each diet change.
3. Feed older infants, children and adults 4 to 6 times daily (27, 53).

a. See Table 9-2, p 177, for composition of Glutarex and Table 9-3, p 178, for nutrient
composition of infant formulas and whole cow's milk.
2. Check diet to determine if it supplies Recommended Dietary Intakes (RDIs) (22) for minerals
and vitamins (Appendices 13 and 14, pp A-14 and A-15).
a. See Table 9-2, p 177, for composition of Glutarex and Appendices 4 through 7, pp A-4 to
A-7, for complete nutrient composition of infant formulas and Appendix 8, p A-8, for
composition of whole cow's milk.
not available.
c. If Glutarex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
supplement diet with needed minerals and vitamins, if laboratory tests indicate need
(Appendix 11, p A-10, for composition of supplements).
B. Osmolarity
b. Osmolarity per gram of Glutarex is listed in Appendix 19, p A-21.
2. If osmolarity is > 450 mosm/L for infants (37), > 750 mosm/kg H2O for children, >
1,000 mosm/L for adults (58), or greater than that tolerated by patient, increase water content
of prescribed medical food mixture and recalculate its osmolarity.
renal solute load.
recalculate.
D. Drug and Nutrient Interactions
1. Monitor all possible drug and nutrient interactions.
2. Anticonvulsant therapy with Depakene ® (valproic acid) may result in gastrointestinal distress,
secondary carnitine deficiency (55), and hyperglycinemia (62).

A. Plasma LYS and TRP Concentrations
1. Initial.
a. Evaluate daily by quantitative methods until plasma concentrations stabilize and
approximate dietary LYS and TRP requirements are known.
2. Ongoing.
b. Evaluate plasma concentrations of LYS and TRP by quantitative methods twice monthly
until the patient is 12 months of age and monthly thereafter.
3. Unacceptable Plasma LYS or TRP Concentration.
a. If LYS or TRP is not detected and patient has ingested full prescription:
1) Increase prescribed amount of LYS or TRP by 25% and reevaluate in 3 days.
2) If either plasma LYS or TRP concentration continues undetected, repeat above
b. If plasma LYS concentration is < 45 µmol/L or TRP is < 15 µmol/L and patient has
ingested full prescription:
1) Increase prescribed amount of LYS or TRP by 5% to 10% and reevaluate plasma
concentration in 1 week.
2) If plasma LYS or TRP concentration remains low, repeat above process until value is
in treatment range.
c. If plasma LYS concentration is > 90 µmol/L or TRP concentration is > 65 µmol/L and
patient is not ill and has not ingested more LYS or TRP or significantly less protein and
energy than prescribed:
1) Decrease prescribed amount of LYS or TRP by 5% to 10% and reevaluate plasma
concentration in 1 week.
2) If plasma LYS or TRP concentration continues elevated, repeat above process until
Warning: Not all laboratories quantitate plasma TRP concentrations. It is essential that
plasma TRP concentrations be assessed to prevent deficiency.
4. If plasma albumin concentration is below normal (Appendix 17, p A-18, free plasma TRP may
be greater than normal (13, 39).
5. If equipment for determining plasma TRP concentration or other plasma amino acid
concentrations is unavailable, see Table 9-4, p 178, for provider of this service.
6. Anticonvulsants such as valproic acid may cause elevated plasma glycine concentration (62).
7. Low plasma concentrations of branched-chain amino acids (BCAAs) indicate inadequate
protein intake.
a. If plasma BCAA concentrations are below normal, increase prescribed Glutarex by 5% to
10% and reevaluate plasma concentrations in 1 week.
B. Plasma Glutaric Acid Concentration
1. At presentation, measure daily until concentration is stabilized in treatment range.
2. Ongoing, measure twice monthly until patient is 12 months of age and monthly thereafter.
3. If equipment for determining plasma glutaric acid concentration is unavailable, see Table 9-4,
p 178, for provider of this service.
C. Urine Organic Acids
1. Initially, measure at presentation; then reevaluate 1 week after nutrition support is begun.
a. Urine organic acid levels are initially useful for diagnosis but do not reflect adequacy of
nutrition support as accurately as plasma concentrations of LYS, TRP, and glutaric acid.
D. Protein Status
1. Evaluate plasma albumin and transthyretin concentrations every 3 months until patient is
1 year of age and 6 months thereafter (Appendix 17, p A-18, for standards).
2. If plasma albumin or transthyretin concentration is below standard:
a. Increase prescribed protein by 5% to 10% and reevaluate plasma albumin or transthyretin
concentration in 1 month. If plasma LYS and TRP concentrations are in treatment range,
use Glutarex to increase protein.
b. Plasma albumin concentration may be in the normal range when plasma transthyretin
shows a clear deficiency (4).
c. If plasma albumin or transthyretin concentration continues below standard, repeat above
process until value is in normal range.
Warning: Hypoalbuminemia (< 3.5 g/dL) may increase effects of some skeletal muscle
relaxants and anticonvulsants (23).
E. Iron Status
1. Plasma ferritin concentration (8).
a. Evaluate hemoglobin and hematocrit concentrations at diagnosis and at 6, 9, and
12 months of age and every 6 months thereafter (Appendix 17, p A-18, for standards).
F. Plasma Free Carnitine Concentration
1. Plasma free carnitine should be evaluated as necessary to maintain normal concentration
(≥ 30 µmol/L).
G. Riboflavin
1. Effectiveness of riboflavin supplementation may be assessed by quantitating urinary glutaric
acid concentrations on same dietary intake of LYS and TRP pre- and post-riboflavin
supplementation (5, 29).
H. Growth Status
b. If length/height or weight remains low, repeat above until usual growth channel is
achieved.
c. Neurologically compromised patients may have difficulty maintaining weight gain equal to
height or linear gain and require frequent monitoring to prevent failure to thrive. Nutrition
intervention may include prescribing an energy intake greater than RDA for age and use
of gastrostomy tube.
I. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of LYS, TRP, protein, and energy before each blood test.
not available.
J. Clinical Summary
XI. Special Concerns

A. Hydration
1. Request parents or caretakers to monitor hydration status at home if neurologic impairment
results in dysarthria or dysphagia.
a. Teach family members clinical signs of impending dehydration (17), including dry mouth,
decreased urine output, lack of tears, sunken eyes, lethargy, poor skin elasticity, and
depressed fontanel in young infants.
b. Use Ketostix ® to monitor hydration status. Normal random urine specific gravity ranges
between 1.002 and 1.006 in infants (65).
B. Dysphagia
1. Severely neurologically impaired patients require nasogastric or gastrostomy tube feedings.
C. Constipation
1. Chronic constipation may be present in nonambulatory patients. Use appropriate methods to
prevent constipation:
a. Increase fluid intake.
b. Increase either fiber-containing foods such as raw fruits, vegetables, dried fruits, and
cooked vegetables or commercially available soluble fiber products.
c. Recommend prune juice (may be mixed with 7-Up ®).
d. Avoid long-term use of laxatives or mineral oil.
XII. Sample Prescriptions

A. Example 1
Establish and fill prescription for 4-month-old girl weighing 6.0 kg (50th percentile) using
Recommended Daily Nutrient Intakes from Table 9-1, p 176, and nutrient contents from
LYS 70 mg/kg x 6.0 kg = 420 mg/day
TRP 14 mg/kg x 6.0 kg = 84 mg
L-Carnitine 145 mg x 6.0 kg = 870 mg
Riboflavin (GA-I) = 100 mg
Medical Food Mixture Measure LYS TRP L-Carnitine Protein Energy
Glutarex-1 97 g 0 0 873 14.6 466
Similac With Iron Ready to Feed 372 mL 420 82 0 5.2 253
Total per day 420 82 873 19.8 719

Total per kg 70 14 145 3.3 126
is ≤ 187 mosm.
B. Example 2
Establish and fill prescription for 7-year-old girl weighing 20 kg using Recommended Daily
Nutrient Intakes from Table 9-1, p 176, and nutrient contents from Tables 9-2 and 9-3, pp 177and
178.
LYS 35 mg/kg x 20 kg = 700 mg/day
TRP 10 mg/kg x 20 kg = 200 mg
L-Carnitine 100 mg/kg x 20 kg = 2,000 mg
Protein 40 g
Energy 2,400 kcal
Fluid 2,400 mL
Riboflavin (GA-I) 100 mg
Medical Food Mixture Measure LYS TRP L-Carnitine Protein Energy
Glutarex-2 70 g 0 0 1,260 21.0 287
L-Carnitine 7.4 mL 0 0 740 0.0 0
Sugar 54 g (4.5 Tbsp) 0 0 0 0.0 216
Add water to make 840 mL (28 fl oz). Offer additional water ad libitum.
Food List Servings

Breads/Cereals 12 360 120 0 10.8 480
Fats 12 72 24 0 1.2 720
Fruits 6 120 30 0 3.6 270
Vegetables 6 120 30 0 3.0 90
Free Foods A 5 25 5 0 0.5 275
Free Foods B 1 0 0 0 0.0 60
Total per day 697 209 2,000 40.1 2,398
1
Add only if plasma free carnitine is below normal.
XIII. Nutrition Support During Febrile Illness or Following Trauma

A. Rationale
2. Well-nourished patients respond to infection and trauma as do normal persons.
B. See Section V, Nutrition Support During Acute Illness, p 167.
Glutaric Aciduria Type I or 2-Ketoadipic Aciduria
Age Nutrient
1,2 2,3
LYS TRP Protein4 Energy4 Fluid5
Infants
0 to < 3 mo 80 - 100 10 - 20 3.50 - 3.00 120 (145 - 95) 150 - 125
3 to < 6 mo 70 - 90 10 - 15 3.50 - 3.00 115 (145 - 95) 160 - 130
6 to < 9 mo 60 - 80 10 - 12 3.00 - 2.50 110 (135 - 80) 145 - 125
9 to < 12 mo 50 - 70 10 - 12 3.00 - 2.50 105 (135 - 80) 135 - 120
(mg/kg) (mg/kg) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 55 - 65 8 - 12 ≥ 30.0 1,300 ( 900 - 1800) 1,300 ( 900 - 1800)
4 to < 7 yr 45 - 55 7 - 11 ≥ 35.0 1,700 (1300 - 2300) 1,700 (1300 - 2300)
7 to < 11 yr 35 - 45 4 - 10 ≥ 40.0 2,400 (1650 - 3300) 2,400 (1650 - 3300)
Women
11 to < 15 yr 30 - 40 4-6 ≥ 50.0 2,200 (1500 - 3000) 2,200 (1500 - 3000)
15 to < 19 yr 20 - 30 3-5 ≥ 55.0 2,100 (1200 - 3000) 2,100 (1200 - 3000)
≥ 19 yr 10 - 20 3-4 ≥ 60.0 2,100 (1400 - 2500) 2,100 (1400 - 2500)
Men
11 to < 15 yr 30 - 40 4-6 ≥ 60.0 2,700 (2000 - 3700) 2,700 (2000 - 3700)
15 to < 19 yr 35 - 45 6-8 ≥ 65.0 2,800 (2100 - 3900) 2,800 (2100 - 3900)
> 19 yr 35 - 45 3-5 ≥ 65.0 2,900 (2000 - 3300) 2,900 (2000 - 3300)
1
Modified from references 1, 11, 12, 18, 21, 36, 44, 51, 60, 66, 68, 70.
2
Initiate therapy with lowest value for age range. Modify prescription based on frequently obtained blood and/or
plasma values and growth in infants and children and frequently obtained plasma values and weight
maintenance in adults.
3
Modified from references 19, 20, 21, 52, 59, 69.
4
5
TABLE 9-2. Nutrient Composition of GLUTAREX ®-1 1, 3 and GLUTAREX ®-2 2, 3
Nutrient Glutarex-1 Glutarex-2

Energy, kcal 480 32 410 13.7
Protein equiv, g 15.00 1.000 30.00 1.000
Nitrogen, g 2.40 0.160 4.80 0.160
Amino acids 15.49 1.032 30.98 1.032
Cystine, g 0.15 0.010 0.30 0.010
Histidine, g 0.42 0.028 0.84 0.028
Isoleucine, g 1.08 0.072 2.16 0.072
Leucine, g 1.68 0.112 3.36 0.112
Lysine, g trace 0 trace 0
Methionine, g 0.30 0.020 0.60 0.020
Phenylalanine, g 0.88 0.059 1.76 0.059
Threonine, g 0.70 0.047 1.40 0.047
Tryptophan, g trace 0 trace 0
Tyrosine, g 0.89 0.059 1.78 0.059
Valine, g 1.22 0.081 2.44 0.081
L-Carnitine, mg 900 60 1800 60
Taurine, mg 40 2.66 50 1.67
Carbohydrate, g 53.0 3.53 35 1.17
Fat, g 21.7 1.45 13 0.43
4 5
Linoleic acid, g 2.00 1.333 1.50 0.050
6 7
0.36 0.024 0.17 0.006
Minerals
Calcium, mg 575 38 880 29
Chloride, mg/mEq 325/9.17 21/0.61 940/26.51 31.33/0.88
Copper, mg 1.1 0.073 1.00 0.033
Chromium, µg 11 0.73 27 0.90
Iodine, µg 65 4.3 100 3.33
Iron, mg 9.0 0.6 13 0.43
Magnesium, mg 50 3.33 225 7.50
Manganese, mg 0.50 0.033 0.80 0.027
Potassium, mg/mEq 675/17.26 45/1.15 1,370/35.04 45.7/1.17
Selenium, µg 20 1.3 35 1.17
Sodium, mg/mEq 190/8.26 12.7/0.55 880/38.28 29.3/1.28
Zinc, mg 8.0 0.53 13 0.43
Vitamins
A, µg RE 420 28 660 22
D, µg 7.50 0.50 7.50 0.25
E, mg α-TE 10.10 0.67 12.10 0.40
K, µg 50 3.33 60 2.00
Biotin, µg 65 4.33 100 3.33
B6, mg 0.75 0.050 1.30 0.043
B12, µg 4.90 0.327 5.00 0.167
Choline, mg 80 5.3 100 3.33
Folate, µg 230 15 430 14.33
Inositol, mg 40 2.67 70 2.33
Niacin, mg 10.0 0.667 16.0 0.53
Riboflavin, mg 0.90 0.06 1.80 0.060
Thiamin, mg 1.90 0.127 3.25 0.108
1 2
3
Approximate packed weight of Glutarex-1 and Glutarex-2 in level, dry US standard household measures:
Glutarex-1 Glutarex-2
1 Tbsp = 7g 8g
1/4 cup = 26 g 32 g
1/3 cup = 30 g 41 g
1/2 cup = 53 g 61 g
1 cup = 105 g 117 g
4 5
6 7
1
TABLE 9-3. Serving Lists for LYS- and TRP-Restricted Diets: Average Nutrient Content per Serving
Food List Nutrient

LYS TRP Protein Energy
Fats 6 2 0.1 60
Fruits 20 5 0.6 45
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 163 25 1.86 68
1
1
1
2
TABLE 9-4. Suppliers of Products and Services for Nutrition Support of Glutaric Aciduria Type I and
2-Ketoadipic Aciduria
Product/Service Provider
Oral riboflavin and thiamine Nature's Bounty, Inc.
90 Orville Drive
Bohemia, NY 117816
(800) 645-5412
(516) 567-9500
Plasma amino acids and urine organic acids1 NeoGen

Abele Business Park
90 Emerson Lane
Suite 1403
(Ask for instructions on how to treat, store, and ship Bridgeville, PA 15017
sample.) (412) 220-2300; FAX (412) 220-0784
Plasma glutaric acid1 Stephen I. Goodman, MD

Biochemical Genetics Laboratory
Dept of Pediatrics
University of Colorado Health Sciences Center
Box C-233
(Ask for instructions on how to treat, store, and ship 4200 E 9th Ave
sample.) Denver, CO 80262
(303) 315-7301
1
The local University School of Medicine medical genetics or metabolic laboratories may also be able to
quantify these analytes.
TABLE 9-5. Serving Lists for LYS- and TRP-Restricted Diets: Gerber ® Baby Foods (Beikost)
Food Weight Approximate LYS TRP Protein Energy

BREADS AND CEREALS
Baked Finger Snacks

Animal crackers, cinnamon graham 34 8-1/2 cookies 30 27 2.0 152
Apple cinnamon cookies 20 2 cookies 30 15 1.6 85
Arrowroot cookies 24 5 cookies 30 27 1.9 109
Banana cookies 20 2-1/2 cookies 29 17 1.4 86
Strawberry fruit bars 18 2 bars 27 16 1.0 73
Cereals, Dry
Barley 7 1-3/4 Tbsp 29 11 0.9 27
Mixed 11 3 Tbsp 29 10 1.1 42
Oatmeal 5 1 Tbsp + 1 tsp 29 9 0.8 20
Oatmeal/banana 7 1-3/4 Tbsp 29 9 0.8 28
Oateal/mixed fruit 8 2 Tbsp 30 9 0.9 33
Rice 10 2 Tbsp + 2 tsp 32 12 0.8 38
Rice/apple 13 3 Tbsp + 1-1/2 tsp 30 12 0.8 51
Rice/apple bits 14 3-3/4 Tbsp 31 12 1.0 55
Rice/banana 12 3 Tbsp 29 12 0.8 46
Rice/mixed fruit 8 2 Tbsp 30 9 0.9 33
Cereals, Jarred
1st Foods ®
Oatmeal 50 3 Tbsp + 1-1/2 tsp 30 11 0.9 28
2nd & 3rd Foods ®
Mixed/applesauce/banana 77 5 Tbsp + 1 tsp 30 8 0.8 66
Oatmeal/applesauce/banana 70 4-3/4 Tbsp 30 8 0.9 58
Rice/applesauce 130 9 Tbsp 30 9 1.0 118
Tender Harvest
Banana/oatmeal/peach 60 4 Tbsp 30 3 0.7 44
Butternut squash/corn 61 4-1/4 Tbsp 30 10 1.2 31
Garden carrots/brown rice 143 10 Tbsp 30 13 1.3 26
Green beans/potatoes 22 1 Tbsp + 1-1/2 tsp 30 7 0.5 14
Spring garden vegetables 47 3-1/4 Tbsp 30 7 0.7 16
Vegetables
1st Foods ®
Peas 15 1 Tbsp 30 5 0.5 7
Potatoes 60 2 Tbsp 30 11 0.6 28
Sweet potatoes 100 7 Tbsp 30 16 1.1 65
2nd Foods ®
Creamed spinach 18 1 Tbsp + 1/4 tsp 30 7 0.6 8
Garden vegetables 23 1 Tbsp + 1 tsp 29 6 0.5 9
Mixed vegetables 42 3 Tbsp 30 5 0.5 15
Peas 14 1 Tbsp 29 5 0.4 7
3rd Foods ®
Green beans/rice 67 4 Tbsp + 1-1/2 tsp 30 11 0.8 28
FRUITS/JUICES
1st Foods ®
Bananas 45 3 Tbsp 20 2 0.5 45
Peaches 83 5-3/4 Tbsp 20 5 0.6 36
Pears 133 9 Tbsp + 1 tsp 20 8 1.3 134
Prunes 133 9 Tbsp + 1 tsp 20 8 1.3 134
2nd Foods ®
Apricot/mixed fruit 107 7 Tbsp + 1 tsp 20 2 0.6 63
Bananas/apples/pears 56 4 Tbsp 20 2 0.5 46
Peaches 83 5-3/4 Tbsp 20 5 0.6 53
Peach cobbler dessert 125 8-3/4 Tbsp 20 10 0.6 95
3rd Foods ®
Hawaiian delight dessert 26 1 Tbsp + 2 tsp 20 3 0.3 23
Fruit Juices
Mixed juice 100 3.2 fl oz 20 3 0.3 48
Orange juice 218 7 fl oz 21 5 1.6 100
Orange/banana/pineapple juice 10 3-1/3 fl oz 21 2 0.5 58
Apple/sweet potato 154 5 fl oz 20 5 0.5 80
Tender Harvest
Pear/wild blueberry 154 10 3/4 Tbsp 20 3 0.6 94
Pears/winter squash 53 3-3/4 Tbsp 20 5 0.6 27
Tropical fruit blend 77 5 Tbsp + 1 tsp 20 2 0.5 57
VEGETABLES
1st Foods ®
Carrots 105 7 Tbsp + 1 tsp 20 6 0.9 37
Green beans 30 2 Tbsp 20 7 0.4 9
Squash 49 3 Tbsp + 1-1/2 tsp 20 6 0.4 17
2nd Foods ®
Carrots 105 7 Tbsp + 1 tsp 20 6 0.8 32
Green beans 38 2-3/4 Tbsp 20 10 0.5 11
Squash 59 4 Tbsp 20 9 0.5 19
3rd Foods ®
Carrots 83 5-3/4 Tbsp 20 7 0.7 24
Squash 80 5-1/2 Tbsp 20 7 0.6 26
Vegetable Dices, Graduates™

Carrots 56 ND 20 4 0.3 13
FREE FOODS A
Dessert, Tropical Fruit

Fruit medley 56 4 Tbsp 5 2 0.1 36
Guava 56 4 Tbsp 5 2 0.1 36
Mango 36 2 Tbsp + 1-1/2 tsp 5 1 0.1 25
Papaya 45 3 Tbsp 5 1 0.1 33
Finger Foods, Graduates

Apples 100 ND 5 5 0.1 48
Peaches 38 ND 5 1 0.2 19
Pears 56 ND 5 5 0.2 30
Fruits
1st Foods ®
Applesauce 43 3 Tbsp 5 1 0.1 23
Pears 33 2 Tbsp + 1 tsp 5 2 0.1 19
Prunes 33 2 Tbsp + 1 tsp 5 2 0.3 33
2nd & 3rd Foods ®
Apple/blueberry 50 3 Tbsp + 1-1/2 tsp 5 1 0.1 25
Bananas 33 2 Tbsp + 1 tsp 5 2 0.2 26
Pears 33 2 Tbsp + 1 tsp 5 2 0.1 18
Pear/pineapple 33 2 Tbsp + 1 tsp 5 1 0.1 18
Plums 100 7 Tbsp 5 3 0.3 74
Prunes 50 3 Tbsp + 1-1/2 tsp 5 4 0.4 38
Tender Harvest
Fruit Juices
Apple/carrot juice 71 2-1/4 fl oz 5 1 0.1 31
Apple/cherry juice 100 3.2 fl oz 5 1 0.1 48
Apple/cranberry juice 100 3.2 fl oz 5 1 0.1 44
Apple/grape juice 100 3.2 fl oz 5 1 0.1 48
Apple juice 100 3.2 fl oz 5 1 0.1 46
Pear juice 100 3.2 fl oz 5 1 0.1 47
Tender Harvest
ND = No data. Prepared from 1998 and 1999 data from Gerber Products, Co., Fremont, MI, 49413.

Level Level Weight
1 tsp = 1/3rd Tbsp = 4.8 g
1 Tbsp = 1/16th cup = 14.3 g
1/4 cup = 4 Tbsp = 57.2 g
1/3 cup = 5-1/3rd Tbsp = 76.2 g
1/2 cup = 8 Tbsp = 114.3 g
2/3 cup = 10 2/3rd Tbsp = 152.5 g
3/4 cup = 12 Tbsp = 171.5 g
1 cup = 16 Tbsp = 228.6 g
1
TABLE 9-5. Serving Lists for LYS- and TRP-Restricted Diets: Table Foods

BREADS AND CEREALS

Cream of Rice 81 1/3 cup 30 11 0.7 42
Cream of Wheat
instant 61 1/4 cup 29 15 1.1 39
Mix'n Eat
plain 70 1/2 packet 35 19 1.4 50
quick 80 1/3 cup 31 17 0.9 43
regular 83 1/3 cup 32 18 1.3 44
Farina ® 87 6 Tbsp 29 18 0.7 44
Oats, regular, quick, and instant 29 2 Tbsp 31 10 0.8 18
Wheatena ® 61 1/4 cup 29 18 1.2 34

All Bran ® 5 1 Tbsp 30 12 0.8 13
Alpha-Bits ® 9 1/3 cup 26 9 0.7 37
Apple Jacks ® 19 2/3 cup 27 11 1.0 72
Bran Buds ® 5 1 Tbsp 29 11 0.7 14
Bran Chex ® 9 3 Tbsp 28 10 1.0 30
40% Bran Flakes ®(Post) 9 3 Tbsp 33 17 1.0 29
Cap'n Crunch ® 24 2/3 cup 33 11 1.2 103
Cheerios ® 5 3 Tbsp + 1 tsp 29 10 0.7 18
Cinnamon Toast Crunch ® 38 1 cup 27 15 1.3 160
Cocoa Krispies ® 13 1/4 cup + 2 Tbsp 30 10 0.7 52
Cocoa Puffs ® 38 1-2/3 cup 32 10 1.3 146
Cookie Crisp ® 20 2/3 cup 30 11 1.0 79
Corn Bran ® 18 1/2 cup 32 10 1.2 62
Corn Chex ® 21 3/4 cup 30 9 1.5 83
Corn Flakes ® 17 3/4 cup 27 8 1.4 66
Crispy Wheat'n Raisins ® 16 1/4 cup + 2 Tbsp 30 18 1.1 56
Froot Loops ® 19 2/3 cup 30 11 1.1 73
Frosted Mini-Wheats ® 9 1-1/3 pieces 30 19 1.0 34
Frosted Rice Krinkles 16 1/2 cup 33 12 0.8 62
Fruit Wheat Squares 20 1/4 cup 29 16 1.4 71
Fruity Pebbles ® 16 1/2 cup 28 10 0.6 66
Golden Grahams ® 20 1/2 cup 32 12 1.1 75
Grape Nut Flakes ® 8 1/4 cup 27 16 0.9 29
Honey Nut Cheerios ® 6 2 Tbsp + 1 tsp 30 16 0.7 22
Honeycomb ® 22 1 cup 33 11 1.3 86
King Vitaman ® 21 1 cup 29 9 1.1 85
Kix ® 12 2/3 cup 29 9 1.1 49
Life ® 3 1 Tbsp 29 7 0.5 10
Lucky Charms ® 8 1/4 cup 30 10 0.7 31
Nutri-Grain ®
corn 21 1/2 cup 33 10 1.7 80
rye 8 3 Tbsp + 1 tsp 30 8 0.7 30
wheat 14 1/4 cup + 1 Tbsp 33 20 1.2 4
Quisp ® 23 3/4 cup 30 10 1.1 93
Raisin Bran ®(Post) 11 3 Tbsp 29 15 1.0 33
Rice Chex ® 13 1/2 cup 29 10 0.7 50
Rice, puffed 10 3/4 cup 28 10 0.7 42
Special K ® 4 2 Tbsp + 1 tsp 30 11 0.8 16
Sugar Frosted Flakes ® 31 3/4 cup + 2 Tbsp 30 10 1.5 117
Sugar Smacks ® 17 7 Tbsp 32 18 1.2 62
Team ® 13 1/4 cup + 1 Tbsp 32 12 0.8 51
Total ® 10 1/4 cup + 1 Tbsp 32 20 1.0 36
Trix ® 21 3/4 cup 27 8 1.1 81
Wheat
puffed 8 2/3 cup 32 18 1.1 28
shredded 9 1/3 oz 31 29 1.0 32
Wheat Chex ® 12 1/4 cup 32 18 1.1 42
Wheaties ® 10 1/3 cup 28 17 0.9 34
Grains
Corn, cooked
cream style 40 2-1/2 Tbsp 30 5 0.7 29
whole kernel 20 2 Tbsp 29 5 0.7 22
Rice, cooked
brown 33 3 Tbsp 31 12 0.8 39
fried 28 2 Tbsp 33 8 0.7 32
pilaf 29 2 Tbsp 31 14 1.2 44
Spanish 45 3 Tbsp 30 9 0.8 39
white
instant 36 3 Tbsp + 1 tsp 29 9 0.8 39
regular 39 3 Tbsp 28 8 0.8 42
Pasta, cooked
Macaroni 24 3 Tbsp 27 15 1.2 36
Noodles, egg 20 2 Tbsp 28 9 0.8 25
Ramen ® noodles 29 3 Tbsp 33 18 1.6 65
Spaghetti 27 3 Tbsp 31 17 1.4 41
Tubers
Potatoes, sweet
baked
no skin, mashed 41 2 Tbsp 33 8 0.7 43
w/ skin, mashed 38 3 Tbsp 32 8 0.6 39
canned, packed in syrup 61 1/4 cup + 1 Tbsp 27 7 0.5 84
Potatoes, white
baked, no skin 23 3 Tbsp 27 7 0.4 21
boiled
no skin 29 3 Tbsp 30 8 0.5 25
w/ skin 29 3 Tbsp 33 9 0.5 26
canned 34 3 Tbsp 29 8 0.5 20
French fries (1/2" x 1/2" x 2"),
fresh 15 3 pieces 32 8 0.6 47
frozen, baked 15 3 pieces 28 7 0.5 49
microwaved, w/ skin 26 2 Tbsp + 2 tsp 33 9 0.5 26
hash browns, frozen, cooked 20 2 Tbsp 33 8 0.6 43
Yams, baked or boiled 51 1/4 cup + 2 Tbsp 30 6 0.8 59
Miscellaneous
Chocolate sauce (Hershey's ®) 38 2 Tbsp 31 10 0.7 82
Chow Mein noodles 11 3 Tbsp 26 13 1.1 56
Ice cream cone, wafer type 4 1 (cone only) 10 5 0.4 17
Jell-O ®, prepared w/ sugar 45 3 Tbsp 30 0 0.7 26
Snack Foods
Breadsticks 12 2 pieces 32 18 1.4 46
Cookies
chocolate chip 12 1 cookie 18 7 0.6 62
fig bar 32 2 cookies 30 16 1.2 115
gingersnap 25 3-1/2 cookies 30 16 1.3 103
Oreo ® 22 2 cookies 26 12 1.1 107
sandwich 28 2-1/2 cookies 29 16 1.3 136
Sno Balls ® 32 3/4 cookie 30 11 1.0 112
Social Tea Biscuits ® 21 4 cookies 30 14 1.2 96
Sugar Wafers ® (Nabisco) 33 6 cookies 27 15 1.3 160
vanilla wafer 24 6 cookies 29 16 1.3 111
Crackers
graham (2" x 2") 18 2-1/2 crackers 31 17 1.4 67
Melba toast 12 2 pieces 33 18 1.6 41
Ritz ® 20 6 crackers 29 16 1.4 99
Ritz Bits ®, cheese 9 13 crackers 28 11 0.9 45
Rykrisp ® 6 1 triple cracker 26 7 0.6 23
saltines 15 5 crackers 30 17 1.4 65
Triscuits ® 16 3-1/2 crackers 29 16 1.4 73
Waverly ® 21 3 crackers 33 18 1.6 104
Doodads ®, original 12 3 Tbsp + 1 tsp 29 13 1.3 58
Doritos ® 18 10 chips 28 19 1.3 88
Fritos ® 22 11 chips 30 18 1.5 120
Popcorn
buttered 16 1-3/4 cups 33 9 1.6 72
caramel 23 2/3 cup 28 8 1.4 88
plain 12 2 cups 30 9 1.5 46
Pringles ® potato crisps 8 4 chips 31 8 0.5 42
Tortilla (6" diameter)
corn 21 1 tortilla 27 6 1.0 30
flour 15 1/2 tortilla 26 14 1.2 48
FATS
Butter
stick 9 2 tsp 6 1 0.1 68
whipped 9 1 Tbsp 6 1 0.1 68
Gravy
mushroom, canned 20 1 Tbsp + 1 tsp 6 3 0.3 10
onion mix, dry 3 2 Tbsp 6 3 0.3 10
Margarine
imitation 14 1 Tbsp 6 1 0.1 50
soft 9 2 tsp 6 1 0.1 68
stick or brick 9 2 tsp 6 1 0.1 67
liquid 10 2 tsp 7 2 0.1 174
Polyrich ® 29 2 Tbsp 5 1 0.1 44
powder 2 1 tsp 8 1 0.1 11
Rich's ® Coffee Rich 29 2 Tbsp 5 1 0.1 44
Olives
black 10 2 olives 6 1 0.1 18
green 10 2 olives 7 2 0.1 12
Catalina 51 3 Tbsp 6 2 0.2 217
French 16 1 Tbsp 6 1 0.1 67
Italian 15 1 Tbsp 7 2 0.1 69
Miracle Whip ® 14 1 Tbsp 4 1 0.1 70
Thousand Island 10 2 tsp 6 1 0.1 39
Tartar sauce 7 1-1/2 tsp 7 2 0.1 37
Cool Whip ®,
extra creamy 3 2 tsp 6 1 0.1 10
regular 5 1 Tbsp + 1 tsp 6 1 0.1 15
Dessert topping w/ sodium caseinate, pressurized 9 2 Tbsp 7 1 0.1 23
Whipped cream, pressurized 2 2 tsp 6 1 0.1 6
FRUITS
Apples
butter 80 1/4 cup 19 3 0.3 148
canned, sweetened, sliced 204 1 cup 22 4 0.4 137
dried 23 1/3 cup 16 3 0.3 69
sauce, canned, sweetened 168 1 cup 19 3 0.3 128
whole, medium 138 1 fruit 17 3 0.3 81
Apricots
dried
cooked, mashed 21 1 Tbsp + 1 tsp 19 5 0.3 18
halves 7 2 18 5 0.3 17
nectar, canned 79 2-1/2 fl oz 20 6 0.3 44
whole 18 1/2 fruit 17 3 0.2 8
Avocadoes, all varieties, mashed 20 1 Tbsp + 1-1/4 tsp 19 4 0.4 33
Banana, sliced 42 3 Tbsp 20 5 0.4 39
Blackberries
canned, heavy syrup 37 2 Tbsp + 1 tsp 20 6 0.5 34
raw 72 1/2 cup 21 6 0.5 38
Blueberries
frozen, sweetened 287 1-1/4 cups 20 6 1.1 233
raw 163 1 cup + 2 Tbsp 20 5 1.1 91
Cherries, canned, heavy syrup
sour, red 117 1/2 cup 19 9 0.9 106
sweet 72 1/2 cup 20 9 0.9 52
Coconut, shredded
dried 7 1 Tbsp + 1 tsp 21 5 0.5 47
dried, sweetened w/ sugar 15 3 Tbsp 21 6 0.6 69
Currants, black 84 3/4 cup 21 5 1.2 53
Dates 33 4 fruits 20 17 0.7 91
Elderberries, raw 76 1/2 cup 19 10 0.5 55
Figs
dried
cooked, mashed 33 2 Tbsp 17 4 0.4 36
uncooked, chopped 17 1 Tbsp + 1 tsp 20 4 0.5 42
whole, large 64 1 fruit 19 4 0.5 47
Grapefruit
canned in juice 124 1/2 cup 22 2 0.9 46
juice, canned, unsweetened 278 9 fl oz 19 6 1.4 106
sections
red and pink 115 1/2 cup 18 2 0.7 37
white 118 1/2 fruit 19 2 0.7 38
Grapes
European, green 120 3/4 cup 18 4 0.8 85
Thompson, seedless, canned, heavy syrup 169 2/3 cup 19 3 0.8 123
Guavas 90 1 fruit 21 6 0.7 46
Kiwi fruit 57 3/4 fruit 19 15 0.6 35
Lemons 33 1/2 fruit 18 3 0.4 9
Mangoes, sliced 54 1/3 cup 22 4 0.3 35
Melons, cubed
cantaloupe 53 1/3 cup 19 3 0.5 18
casaba 56 1/3 cup 21 4 0.5 15
honeydew 112 2/3 fruit 21 3 0.5 39
Nectarines 67 1/2 fruit 21 2 0.6 33
Oranges
juice
fresh 248 8 fl oz 22 5 1.7 111
canned 249 8 fl oz 20 5 1.5 104
sections 45 1/4 cup 21 4 0.4 21
Papayas
cubed 70 1/2 cup 18 6 0.4 27
Peaches
canned, heavy syrup, sliced 128 1/2 cup 19 1 0.6 95
dried, halves 13 1 15 0 0.5 31
sliced 85 1/2 cup 20 2 0.6 37
Pears
canned, heavy syrup 255 1 cup 18 18 0.5 189
dried
cooked 64 1/4 cup 20 17 0.6 81
halves 35 2 23 17 0.7 91
sliced 124 3/4 cup 17 11 0.5 73
Persimmons, Japanese 55 1/3 fruit 18 6 0.3 39
Pineapple
diced 77 1/2 cup 19 4 0.3 38
juice bar, frozen 74 1 bar 19 4 0.3 70
canned, heavy syrup, tidbits or crushed 128 1/2 cup 21 7 0.5 100
Plantains, cooked, sliced 51 1/3 cup 18 5 0.4 59
Plums
purple, canned, heavy syrup 258 1 cup 21 21 0.9 230
sliced 109 2/3 cup 19 2 0.9 60
Prunes
dried
cooked 70 1/3 cup 18 2 0.8 75
uncooked 34 4 pieces 20 2 0.9 80
Raisins
golden 27 3 Tbsp 20 4 0.9 82
regular, seedless 27 3 Tbsp 19 4 0.9 82
Raspberries
frozen, red, sweetened 63 1/4 cup 18 5 0.4 65
raw 61 1/2 cup 23 6 0.6 30
Rhubarb, cooked, sweetened 119 1/2 cup 18 6 0.6 139
Strawberries
frozen, sweetened, sliced 84 1/3 cup 19 5 0.4 81
sliced 74 1/2 cup 19 5 0.5 22
Tangerines
whole 63 3/4 fruit 20 4 0.4 28
Watermelon, cubed 30 3 Tbsp 19 2 0.2 10
VEGETABLES
Asparagus
fresh or frozen, cooked 15 1 spear 19 4 0.4 6
raw 15 1 spear 19 4 0.4 4
Bamboo shoots, canned, sliced 22 3 Tbsp 18 4 0.3 3
Beans
snap green
canned 34 1/4 cup 19 4 0.4 7
fresh, cooked 23 3 Tbsp 21 5 0.4 8
sprouts, mung (seed attached to sprout)
cooked 16 2 Tbsp 20 4 0.3 3
raw 13 2 Tbsp 22 5 0.4 4
yellow wax, canned 33 2 Tbsp 18 4 0.4 7
Beets
greens, cooked, chopped 27 3 Tbsp 20 11 0.7 7
red, sliced
fresh, canned, cooked 53 1/4 cup + 1 Tbsp 20 7 0.6 16
pickled 75 1/3 cup 22 7 0.6 50
cooked 13 1 Tbsp + 1 tsp 19 4 0.4 4
raw 13 1 Tbsp + 1 tsp 20 4 0.4 4
Brussels sprouts, fresh or frozen, cooked 16 1 Tbsp + 2 tsp 19 5 0.4 6
Cabbage, shredded
Chinese (Pak-choi)
cooked 21 2 Tbsp 20 3 0.3 3
raw 23 1/3 cup 21 4 0.3 3
red
cooked 37 1/4 cup 19 4 0.4 8
raw 35 1/2 cup 20 4 0.4 8
Carrots
canned, sliced 73 1/2 cup 18 5 0.5 17
cooked 49 1/4 cup + 1 Tbsp 21 6 0.5 22
sliced 55 1/2 cup 22 6 0.6 24
Cauliflower
diced, cooked
fresh 20 2 Tbsp + 2 tsp 20 5 0.4 5
frozen 13 1 Tbsp + 2 tsp 13 3 0.2 3
raw 19 3 Tbsp 20 5 0.4 5
Celery, diced
cooked 99 2/3 cup 20 7 0.5 15
raw 79 2/3 cup 21 7 0.5 13
Chard, Swiss, cooked 22 2 Tbsp 23 4 0.4 4
fresh 36 3 Tbsp 19 5 0.4 5
frozen 14 1 Tbsp + 1 tsp 20 5 0.4 5
Eggplant, cubed
cooked 48 1/2 cup 19 4 0.4 13
raw 41 1/2 cup 21 4 0.5 11
Endive, shredded 33 2/3 cup 21 2 0.4 6
Horseradish 7 2-1/2 Tbsp 20 5 0.3 4
Kale, cooked
fresh 16 2 Tbsp 19 4 0.3 5
frozen 11 1 Tbsp + 1 tsp 19 4 0.3 3
Kohlrabi, sliced
cooked 31 3 Tbsp 18 3 0.6 9
raw 35 1/4 cup 20 4 0.6 10
Leeks, diced
cooked 52 1/2 cup 22 3 0.4 16
raw 26 1/4 cup 20 3 0.4 16
Lettuce, shredded
iceberg 28 1/2 cup 21 2 0.3 4
Romaine 18 1/3 cup 19 2 0.3 3
Mushrooms
Agaricus bisporus, sliced
cooked or canned 9 2 Tbsp 19 4 0.2 2
raw 9 2 Tbsp 19 4 0.2 2
Shitake
cooked, pieces 48 1/3 cup 22 1 0.7 27
dried 5 1-1/2 mushrooms 18 2 0.5 17
cooked 19 2 Tbsp + 1/2 tsp 20 5 0.4 3
raw 18 1/4 cup + 1 Tbsp 22 5 0.5 5
Okra, cooked, sliced 27 2 Tbsp + 2 tsp 20 4 0.5 8
Onions
cooked 53 1/4 cup 23 7 0.5 15
flakes 5 1 Tbsp 21 6 0.5 16
raw, diced 40 1/4 cup 22 7 0.5 14
rings, canned 23 1 cup 10 5 0.4 82
Parsnips, cooked 39 1/4 cup 20 5 0.5 32
Peas, green, cooked, canned, frozen 10 1 Tbsp 18 2 0.3 5
Peppers
green, sweet, diced
cooked 68 1/2 cup 19 5 0.4 12
raw 50 1/2 cup 19 6 0.4 13
jalapeño, canned, cooked 51 1/4 cup + 2 Tbsp 18 5 0.4 12
Pickle, cucumber
dill
relish 14 1 Tbsp 4 1 0.1 3
whole, small 60 1 pickle 17 3 0.4 7
sweet
relish 16 1 Tbsp 3 1 0.1 22
sliced 60 2 slices 17 3 0.4 88
Pumpkin
canned 31 2 Tbsp 18 4 0.3 10
cooked 34 3 Tbsp 20 5 0.4 35
Radishes, red, sliced 58 1/2 cup 20 2 0.3 10
Rutabaga
raw, cubed 46 1/3 cup 18 6 0.6 17
Sauerkraut 44 3 Tbsp 19 4 0.4 8
Shallots, chopped 17 1 Tbsp + 2 tsp 21 5 0.4 12
Spinach, chopped
raw 11 3 Tbsp 19 4 0.3 2
fresh or frozen, cooked 37 3 Tbsp + 1 tsp 19 3 0.3 7
sliced 33 1/4 cup 21 4 0.4 7
winter
acorn, baked, cubed 51 1/4 cup 21 5 0.6 29
butternut, baked, cubed 68 1/3 cup 22 9 0.6 27
Hubbard, baked, cubed 38 1/3 cup 21 8 0.9 19
spaghetti, boiled 101 2/3 cup 22 9 0.7 29
Taro, cooked
leaves 15 1 Tbsp + 2 tsp 20 4 0.4 4
root, sliced 75 1/2 cup 17 6 0.4 107
Tomato
catsup 26 1 Tbsp + 1 tsp 21 5 0.5 27
fresh, canned, cooked 45 3 Tbsp 19 4 0.5 11
juice 92 3 fl oz 20 5 0.7 16
paste 19 1 Tbsp + 1/2 tsp 21 5 0.7 16
purée 39 2-1/2 Tbsp 19 4 0.7 16
sauce
marinara 45 3 tbsp 20 5 0.7 31
w/ onions, green peppers, and celery 46 3 Tbsp 17 4 0.6 14
stewed, canned 64 1/4 cup 22 5 0.6 17
whole, chopped 59 1/3 cup 20 4 0.5 11
Turnips
greens, cooked, chopped 27 3 Tbsp 20 5 0.3 5
root, diced
cooked 78 1/2 cup 22 5 0.6 14
raw 60 1/2 cup 21 5 0.5 17
Vegetable cocktail juice (V8 ®) 39 2-1/2 Tbsp 19 4 0.7 16
Asparagus, Cream of 21 1 Tbsp + 1 tsp 19 5 0.4 14
Celery, Cream of 31 2 Tbsp 19 5 0.4 23
Mushroom, Cream of 24 1-1/2 Tbsp 20 5 0.4 24
Onion 15 1 Tbsp 22 7 0.5 7
Potato, Cream of 31 2 Tbsp 21 6 0.4 19
Tomato 47 3 Tbsp 19 8 0.8 32
Tomato Bisque 31 2 Tbsp 22 6 0.6 30
Vegetable, Chunky, Ready To Serve 25 1 Tbsp + 2 tsp 20 3 0.4 13
Vegetable, Old Fashioned 26 1 Tbsp + 2 tsp 21 3 0.5 14
Vegetarian Vegetable 26 1 Tbsp + 2 tsp 21 3 0.4 15
FREE FOODS A
Beverages
Chocolate drink powder (Quik ®) 3 1 tsp 4 1 0.1 11
Grape juice, canned 63 2 fl oz 6 10 0.4 38
Lemon juice 92 3 fl oz 5 1 0.4 19
Orange juice
canned 62 2 fl oz 5 1 0.4 26
Orange-grapefruit juice, canned 62 2 fl oz 5 1 0.4 27
Papaya nectar 93 3 fl oz 7 2 0.2 53
Pear nectar 125 4 fl oz 5 3 0.1 75
Tangerine juice, frozen, diluted 90 3 fl oz 6 1 0.4 42
Apples, dried, cooked 42 3 Tbsp 6 1 0.1 24
Apple pie filling 61 1/4 cup 4 1 0.1 68
Blueberries, raw 36 1/4 cup 4 1 0.2 52
Cranberry sauce sweetened w/ sugar 132 1/2 cup 6 1 0.3 209
Fruit ices 24 2 Tbsp 5 1 0.1 3
Grapes, slipskin 48 20 grapes 6 2 0.3 30
Guava sauce 59 1/4 cup 5 2 0.2 21
Jams and preserves 20 1 Tbsp 5 1 0.1 54
Marmalade 19 1 Tbsp 5 1 0.1 50
Loquats 20 2 fruits 6 1 0.1 10
Miscellaneous
Licorice 5 1/2 piece 4 2 0.2 17
M&M ® Candy, plain 1 1 piece 3 1 0.1 4
Raisins, chocolate covered 1 1 raisin 4 1 0.1 6
Sorbet
peach 24 2 Tbsp 5 0 0.1 30
pineapple 15 1 Tbsp 4 1 0.1 14
strawberry 30 2 Tbsp 5 1 0.1 29
Tapioca, dry 31 3 Tbsp 6 3 0.2 109
Vegetables
Chives 3 1 Tbsp 4 1 0.1 1
Cucumbers, pared, sliced 26 1/4 cup 6 1 0.1 4
Radishes, white icicle, sliced 21 1/4 cup 6 0 0.1 4
FREE FOODS B
These foods contain little or no LYS or TRP. They may be used as desired if patient is not overweight and if they do not depress appetite for
prescribed foods.
Beverages
Carbonated drinks
cola 123 4 fl oz 0 0 0.0 50
cream soda 124 4 fl oz 0 0 0.0 63
Dr Pepper ® 31 1 fl oz 0 0 0.0 13
ginger ale 122 4 fl oz 0 0 0.0 41
grape soda 124 4 fl oz 0 0 0.0 53
lemon-lime soda 123 4 fl oz 0 0 0.0 49
orange soda 124 4 fl oz 0 0 0.0 60
root beer 123 4 fl oz 0 0 0.0 50
Fruit drink (Hi-C ®) 124 4 fl oz 0 0 0.0 58
Fruit juice drink 124 4 fl oz 2 0 0.1 62
Gatorade ® Thirst Quencher 121 4 fl oz 0 0 0.0 30
Kool-Aid ®, prepared w/ sugar 123 4 fl oz 0 0 0.0 49
Lemonade 123 4 fl oz 1 0 0.1 49
Lime juice 31 1 fl oz 1 0 0.1 6
Orange drink powder (Tang ®) 12 1 Tbsp 0 0 0.0 47
Strawberry drink powder (Quik ®) 8 1 Tbsp 0 0 0.0 33
Desserts/Sweeteners
Candies
candy corn 8 5 pieces 1 0 0.0 29
gumdrops 20 4 pieces 0 0 0.0 28
hard candy 10 2 pieces 0 0 0.0 39
jelly beans 28 10 pieces 0 0 0.0 103
Jellies 20 1 Tbsp 0 0 0.0 54
Lemon pudding, canned (Hunt's ®) 121 1 container 0 0 0.0 151
Popsicle ®, twin 128 1/2 popsicle 0 0 0.0 95
Miscellaneous
Butterscotch chips 1 1 piece 2 0 0.0 3
Fun fruits 26 1 piece 2 1 0.1 100
Honey 21 1 Tbsp 2 1 0.1 64
Lard 13 1 Tbsp 0 0 0.0 115
Oil
olive 13 1 Tbsp 0 0 0.0 119
vegetable 14 1 Tbsp 0 0 0.0 120
Richwhip ® liquid 14 1 Tbsp 0 0 0.0 40
Sugar
brown 14 1 Tbsp 0 0 0.0 52
table 12 1 Tbsp 0 0 0.0 48
Syrup
maple 20 1 Tbsp 0 0 0.0 50
table 20 1 Tbsp 0 0 0.0 50
Tallow, beef 13 1 Tbsp 0 0 0.0 115
1
For composition of very-low-protein foods, see Appendix 12, p A-11.
192 Glutaric Aciduria Type I or 2-Ketoadipic Aciduria
TABLE 9-6. Glutaric Aciduria Type I or 2-Ketoadipic Aciduria Clinical Summary Sheet
Date of Birth: __________/__________/__________ Date of Diagnosis: ___________/__________/__________

Medications: Supplements:

Length/ Weight Head Free Glutaric LYS TRP Hgb Hct Ferritin Albumin/ Urinary LYS TRP Protein Energy
Height Circum Carnitine Acid Transthyretin Organic
(mo/d/yr) (cm) (kg) (cm) (µmol/L) (ng/mL) (µmol/L) (µmol/L) (g/dL) (%) (ng/mL) (g/dL / mg/dL) Acids (mg) (mg) (g) (kcal)
REFERENCES
1. Abernathy RP, Speirs M, Engel RW, Moore ME: Effects of several levels of dietary protein and amino acids on
nitrogen balance of preadolescent girls. Am J Clin Nutr 1968;19:407-414.
2. Amir N, Elpeleg ON, Shalev RS, Christensen E: Glutaric aciduria type I. Enzymatic and neuroradiologic
investigations of two kindreds. J Pediatr 1989;114:983-989.
3. Applegarth DA, Edelstein AD, Wong LTK, Morrison BJ: Observed range of assay values for plasma and
cerebrospinal fluid amino acid levels in infants and children aged 3 months to 10 years. Clin Biochem
1979;5:173-178.
Dis 2000;23 Suppl 1:29A.
5. Baric I, Zchocke J, Christensen E, et al: Diagnosis and management of glutaric aciduria type I. J Inher Metab Dis
1998;21:326-340.
1996.
7. Bergman I, Finegold D, Gartner JC: Acute profound dystonia in infants with glutaric acidemia. Pediatrics
1989;83:228-234.
8. Bohles H, Ullrich K, Endres W, et al: Inadequate iron availability as a possible cause of low serum carnitine
concentrations in patients with phenylketonuria. Eur J Pediatr 1991;150:425-428.
9. Brandt NJ, Brandt S, Christensen E, et al: Glutaric aciduria in progressive choreoathetosis. Clin Genet 1978;13:77-
80.
10. Brandt NJ, Gregersen N, Christensen E, et al: Treatment of glutaryl-CoA dehydrogenase deficiency (glutaric
aciduria). J Pediatr 1979;94:669-673.
11. Clark HE, Kenney MA, Goodwin AF, et al: Effect of certain factors on nitrogen retention and lysine requirements of
adult human subjects. IV. Total nitrogen intake. J Nutr 1963;81:223-229.
12. Clark HE, Mertz ET, Kwong EH, et al: Amino acid requirements of men and women. I. Lysine. J Nutr
1957;62:71-82.
13. Curzon G, Kantamaneni BD, Winch J, et al: Plasma and brain tryptophan changes in experimental acute hepatic
failure. J Neurochem 1973;21:137-145.
14. Dunger DB, Snodgrass GJAI: Glutaric aciduria type I presenting with hypoglycaemia. J Inher Metab Dis
1984;7:122-124.
15. Duran M, Beemer FA, Wadman SK, et al: A patient with α-ketoadipic and α-aminoadipic aciduria. J Inher Metab
Dis 1984;7:61.
17. Finberg L: Assessing the clinical clues to dehydration. Contemp Pediatr 1990;7:45-57.
18. Fisher H, Brush MK, Griminger P: Reassessment of amino acid requirements of young women on low nitrogen
diets. I. Lysine and tryptophan. Am J Clin Nutr 1969;22:1190-1196.
19. Fisher H, Brush MK, Shapiro R, et al: Amino acid balance in the adult: High-nitrogen low-tryptophan diets. J Nutr
1963;81:230-234.
20. Fomon SJ, May CD: Metabolic studies of normal full-term infants fed pasteurized human milk. Pediatrics
1958;22:101-114.
21. Fomon SJ, Thomas LN, Filer LJ Jr, et al: Requirements for protein and essential amino acids in early infancy. Acta
Paediatr Scand 1973;62:33-45.
23. Garabédian-Ruffalo S, Ruffalo RL: Drug and nutrient interactions. Am Fam Phys 1986;33:165-174.
24. Goodman SI, Frerman FE: Organic acidemias due to defects in lysine oxidation: 2-ketoadipic acidemia and
glutaric acidemia. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of Inherited Disease, ed 8. New
York: McGraw-Hill Medical Publishing Division, 2001, pp 2195-2204.
26. Haworth JC, Booth PA, Chudley AE: Phenotype variability in glutaric aciduria type I. Report of fourteen cases in
five Canadian Indian kindreds. J Pediatr 1991;118:52-58.
mixture and different amounts of single dose ingested. A case report. Eur J Pediatr 1994;153:502-503.
28. Heyes MD: Hypothesis: A role for quinolinic acid in the neuropathy of glutaric aciduria type I. Can J Neurol Sci
1987;14:441-443.
29. Hoffman GF: Disorders of lysine catabolism and related cerbral organic acid disorders. In Fernandes J, et al (eds):
Inborn Metabolic Diseases: Diagnosis and Treatment, ed 3. New York: Springer-Verlag, 2000, pp 241-253.
30. Hoffman GF, Tretz FK, Barth PG, et al: Macrocephaly: An important indication for organic acid analysis. J Inher
Metab Dis 1991;14:329-332.
31. Hoffman GF, Zschocke J: Glutaric aciduria type I: From clinical, biochemical, and molecular diversity to
successful therapy. J Inher Metab Dis 1999;22:381-391.
32. Hyman DB, Tanaka K: Specific glutaryl-CoA dehydrogenase activity is deficient in cultured fibroblasts from glutaric
aciduria patients. J Clin Invest 1984;73:778-784.
33. Jones EM, Baumann CA, Reynolds MS: Nitrogen balances of women maintained on various levels of lysine. J Nutr
1956;60:549-562.
35. Kylerrman M, Steen G: Glutaric aciduria. A "common" metabolic disorder. Arch Fri Pediatr 1980;37:279-81.
1982.
38. MacLean WC, Placko RP, Graham GG: Fasting plasma free amino acids of infants and children consuming cow
milk proteins. Johns Hopkins Med J 1978;142:147-151.
39. Madras BK, Cohen EL, Messing R, et al: Relevance of free tryptophan in serum to tissue tryptophan concentration.
Metabolism 1974;23:1107-1116.
1987;1:1-17.
41. Meites S (ed): Pediatric Clinical Chemistry, ed 3. Washington, DC: AAAC Press, 1989.
42. Monavari AA, Naughten ER: Prevention of cerebral palsy in glutaric aciduria type I by dietary management. Arch
Dis Child 2000;82:67-70.
43. Morton DH, Bennett MJ, Seargeant LE, et al: Glutaric aciduria type I: A common cause of episodic encephalopathy
and spastic paralysis in the Amish of Lancaster County, Pennsylvania. Am J Med Genetics 1991;41:89-95.
44. Ohkohchi N, Andoh J, Ohi R, Mori S: Defined formula diets alter characteristics of the intestinal transport of amino
45. Peng H, Shinka t, Inoue Y, et al: Asymptomatic alpha-ketoadipic aciduria detected during a pilot study of neonatal
urine screenings. Acta Paediatr 1999;88:911-914.
46. Pineda O, Torun B, Viteri FE, Arroyave G: Protein quality in relation to estimates of essential amino acid
requirements. In Bodwell CE, et al (eds): Protein Quality in Humans: Assessment and in Vitro Estimation.
Westport, Conn: Avi Publishing Co Inc, 1981.
DC: US Dept of Agriculture, Agricultural Research Services, 1976.
1955;56:231-251.
49. Przyrembel H: Defects of lysine degradation. In Fernandes J, et al (eds): Inborn Metabolic Diseases: Diagnosis and
Treatment. New York: Springer-Verlag, 1990, pp 301-310.
50. Przyrembel H, Bachmann D, Lombeck I, et al: Alpha-ketoadipic aciduria, a new inborn error of lysine metabolism:
Biochemical studies. Clin Chim Acta 1975;58:257-269.
51. Rose WC: The amino acid requirements of adult man. Nutr Abstr Rev 1957;27:631-647.
52. Rose WC, Lambert GF, Coon MJ: The amino acid requirements of man. VII. General procedures: The tryptophan
requirement. J Biol Chem 1954;211:817-827.
54. Seccombe DW, James L, Booth F: L-carnitine treatment in glutaric aciduria type I. Neurology 1986;36:264-267.
55. Shapira Y, Gutman A: Muscle carnitine deficiency in patients using valproic acid. J Pediatr 1991;118:646-649.
Publisher, 1976.
1983;7:280-288.
59. Snyderman SE, Boyer A, Phansalkar SV, et al: Essential amino acid requirements of infants: Tryptophan. Am J
Dis Child 1961;102:163-167.
60. Snyderman SE, Norton PM, Fowler DI, Holt LE: The essential amino acid requirements of infants: Lysine. Am J
Dis Child 1959;97:175-185.
1989;143:828-832.
62. Stumpf DA, Parker WD, Angelini C: Carnitine deficiency, organic acidemias and Reye's syndrome. Neurology
1985;35:1041-1045.
63. Sturman JA, Applegarth DA: Automated amino acid analysis. In Boulton AA, et al (eds): Neuromethods: Amino
Acids, vol 3. Totowa, NJ: Humana Press, 1985.
64. Superti-Fuerga A, Hoffman GF: Glutaric aciduria type I (glutaryl-GA-dehydrogenase deficiency): Advances and
unanswered questions. Eur J Pediatr 1997;156:821-828.
65. Tietz NW (ed): Textbook of Clinical Chemistry. Philadelphia: WB Saunders Co, 1986.
66. Torun B, Pineda O, Vitera FE, Arroyave G: Use of amino acid composition data to predict protein nutritive value
for children with specific reference to new estimates of their essential amino acid requirements. In Bodwell CE, et
al (eds): Protein Quality in Humans. Assessment and in Vitro Estimation. Westport, Conn: Avi Publishing Co Inc,
1981.
67. Ullrich K, Flott-Rahmel B, Schluff P, et al : Glutaric aciduria type I: Pathomechanisms of neurodegeneration.
68. Yannicelli S, Rohr F, Warman ML: Nutrition support for glutaric acidemia type I. J Amer Diet Assoc
1994;94:183-191.
69. Young VR, Hussein MA, Murray E, Scrimshaw NS: Plasma tryptophan response curve and its relation to
tryptophan requirements of young adult men. J Nutr 1971;101:45-60.
70. Young VR, Tontisirin K, Ozalp I, et al: Plasma amino acid response curve and amino acid requirements in young
men: Valine and lysine. J Nutr 1972;102:1159-1170.
71. Zempleni J, Galloway JR, McCormick, DB: Pharmacokinetics of orally and intravenously administered riboflavin in
healthy humans. Am J Clin Nutr 1996;63:54-66.
PROTOCOL 10 — Glutaric Acidemia Type II (Multiple Acyl-CoA Dehydrogenase
Deficiency)

PROVIMIN ® Protein-Vitamin-Mineral Formula Component With Iron
I. Introduction (13, 44)
Glutaric acidemia type II (GA-II), or multiple acyl-CoA dehydrogenase deficiency, is an inherited
disorder characterized by hypoketotic or nonketotic hypoglycemia and metabolic acidosis,
pathologically by fatty degeneration of liver parenchymal cells, renal tubular epithelium, and
myocardium, and biochemically by the accumulation of metabolites of compounds oxidized by
enzymes that transfer electrons to electron transfer flavoprotein (ETF). In most cases the disorder is
due to the deficiency of either ETF or electron transfer flavoprotein ubiquinone oxidoreductase (ETF-
QO) (Figure I), but in some cases the disorder may be due to an as yet undefined abnormality in flavin
metabolism or transport. Complete deficiency of ETF-QO is often associated with congenital
anomalies, the most frequent and characteristic being cysts, and dysplasia of the kidneys. All forms of
the disease are transmitted as autosomal recessive traits. Most patients with severe disease do not
survive the first few weeks of life (37). While different degrees of enzyme deficiency have been shown
to cause all three clinical forms of the condition, ETF-QO deficiency appears to be more common in
patients with congenital anomalies (43).
Although there are no accurate figures of incidence, GA-II is probably one of the more common inborn
errors.
Very-long chain acyl-CoA
Medium-chain acyl-coA
Fat
(n) Long-chain acyl-CoA
Short-chain acyl-CoA
Isovaleryl-CoA Leucine
Isoleucine, valine 2-Methylbutyrl-CoA (n)
(n) Glutaryl-CoA Lysine, tryptophan
Dimethylglycine (n)
Sarcosine
Electron Transfer Flavoprotein (ETF)
ETF-Ubiquinone Oxidoreductase
H+ + NADH 1/2 O2 + 2 H+
Cytochrome C
Complex I Q Complex III Complex IV
NAD+ H2O
Complex II
(n) = Several steps
Succinate Fumarate = Enzyme defect
+
Figure I. Metabolism in GA II. NAD , NADH = nicotinamide adenine dinucleotide, oxidized and
reduced forms. Q = ubiquinone (coenzyme Q). Complexes I - IV of the respiratory chain
(Modified from reference 9).
II. Outcome of Nutrition Support (13)

Patients who present within a few days of birth usually die within the first few months of life (16,17).
Diets low in fat and protein with supplements of carnitine and riboflavin have not been successful.
Nutrition support with riboflavin, carnitine, and diets low in protein and fat has been more successful
for patients with milder or later-onset disease than for patients with early onset disease. Treatment
with oral riboflavin (100 to 300 mg/day) has been effective in a few patients, including a woman whose
organic aciduria and sarcosinuria developed only during pregnancy and intercurrent infections. With
riboflavin administration during pregnancy, she delivered two normal offspring (23).
© 2001 Ross Products Division Glutaric Acidemia Type II 199

A. The Defect (13)
1. GA II may result from one of several defects:
a. ETF-QO.
b. ETF:
1) the α-subunit.
2) the ß-subunit (49).
3) Excess lability of ETF (49).
B. Differential Diagnosis (13, 15, 28, 46, 50)
1. Neonatal onset with congenital anomalies.
a. Clinical manifestations (16, 17) include ± prematurity; presentation within first 24 to
48 hours of life; anomalies of external genitalia, including hypospadias and chordee; facial
dysmorphism (high forehead, low-set ears, hypertelorism, hypoplastic midface) (5, 8),
hepatomegaly; hypotonia; muscular defects of abdominal wall; "sweaty-feet" odor (8);
± palpably enlarged kidneys; and rocker bottom feet.
b. Most of these infants die within 1st week of life; renal cysts may be observed on
autopsy (5).
2. Neonatal onset without congenital anomalies.
a. Clinical manifestations that ± develop within 1st few days of life; hepatomegaly,
hypotonia, "sweaty feet" odor, and tachypnea.
b. Patients who have survived beyond 1st week of life, because of prompt diagnosis and
treatment, have died within a few months, usually with severe cardiomyopathy resulting
from lipid storage (9, 11, 14).
c. A few infants, hypoglycemic in newborn period, have later developed symptoms typical of
Reye's syndrome.
3. Mild or later onset (ethylmalonic-adipic aciduria).
a. Clinical manifestations include onset any time during 1st few years of life; proximal
myopathy; vomiting; and hepatomegaly.
4. Laboratory evaluation (8, 11, 13, 15, 20, 28)
a. Routine results include hyperammonemia (< 300 µmol/L); hypoglycemia without ketonuria
or ketonemia; metabolic acidosis, often with increased anion gap; elevated serum
transaminases; ± prolonged prothrombin and partial thromboplastin times; and elevated
plasma lactic acid concentration.
b. Urine organic acid values may be abnormal for various combinations of following: adipic,
dodecanedioic, ethylmalonic, glutaric, 2-hydroxyglutaric, 3-hydroxyisovaleric,
5-hydroxyhexanoic, isobutyric, isovaleric, 2-methylbutyric, sebacic, and suberic.
Isobutrylglycine, isovalerylglycine, and 2-methylbutyrylglycine may also be present (3, 4,
13, 15, 20, 43)
c. Serum sarcosine may be elevated.
d. Pancytopenia (25).
5. Prenatal diagnosis is available (6, 24, 26, 39, 49).
IV. Rationale for Nutrition Support (13)

A. Correct Primary Imbalance in Metabolic Relationships (31, 34, 35).
1. Restrict dietary intake of fat to 20% to 25% of energy (9, 31).
2. Restrict dietary intake of intact protein to decrease excess essential isoleucine (ILE), leucine
(LEU), lysine (LYS), tryptophan (TRP), and valine (VAL).
3. Some, but not all, investigators supplement with glycine (GLY) to enhance loss of acyl
compounds (38, 45).
4. Provide adequate energy for normal growth, maintenance, and prevention of catabolism.
B. Supply "Conditionally Essential" Nutrients
1. Supplement L-carnitine to maintain free plasma carnitine in normal range (9, 10, 11, 22, 30,
34, 35, 40, 45, 46, 49).
2. Possible deleterious effects of L-carnitine supplementation were reported by Green et al in
1991 (18).
200 Glutaric Acidemia Type II © 2001 Ross Products Division

C. Stabilize Altered Enzyme Protein
1. Supplement with oral riboflavin (7, 19, 21, 23, 34, 35, 45, 49).

A. Blood Glucose and Plasma Carnitine
1. Maintain normal blood glucose concentrations.
2. Maintain normal plasma free carnitine concentration ≥ 30 µmol/L (40, 48).

in adults.
C. Avoid Lipid Storage in Liver and Muscles (33)
D. Avoid Hyperammonemia and Metabolic Acidosis
E. Prevent Presence of Organic Acids in Urine
F. Prevent Catabolism

A. Energy (13)
2. Requirements vary widely.
Warning: Inadequate energy intake will result in growth failure (27).
B. Fat
1. Prescribe amount of total fat that promotes goals of nutrition support.
a. Supply 20% to 25% of total daily energy as fat.
b. Prescribe 3% of total energy as linoleic acid and 1.0% as α-linolenic acid (12).
Warning: Essential fatty acid deficiency may occur if intakes of linoleic acid and
α−linolenic acid are inadequate.
C. Protein
1. Prescribe amount that promotes normal growth without exceeding tolerance for ILE, LEU,
LYS, TRP, and VAL (Table 10-1, p 203).
Warning: Inadequate protein will result in growth failure.
D. Carbohydrate
1. Prescribe remaining energy as carbohydrate.
E. Fluid
F. L-Carnitine
1. Prescribe amount that maintains normal plasma free carnitine concentrations ≥ 30 µmol/L.
a. Amounts of 50 to 300 mg/kg have been suggested.
G. GLY
1. Prescribe 100 to 150 mg/kg/day (43).

H. Riboflavin
1. Prescribe 100 to 300 mg/day oral riboflavin, depending on age. Prescribe 100 mg/day for
infant, 200 mg/day for child, and 300 mg/day for adult.
I. Fasting
1. Prevent infants from fasting > 4 hours, children > 6 hours, and adults > 8 hours.

A. Fat
1. Calculate grams of fat required to provide 20% to 25% of energy prescription (Table 10-1,
p 203).
2. Determine amount of soy or canola oil (Appendix 10, p A-9) required to supply fat, linoleic
acid and α-linolenic acids.
B. Protein
1. Calculate grams of protein required (Table 10-1, p 203).
2. Calculate amount of ProViMin Protein-Vitamin-Mineral Formula Component With Iron,
beikost, or table foods (Tables 10-2 and 10-3, pp 203-204) required to fill the protein
prescription.
a. Use ProViMin until 2nd birthday due to iron it supplies. After 2nd birthday, use skim milk
(Table 10-3, p 204).
b. Weigh ProViMin powder on scale that reads in grams because of variability of household
measuring equipment (Practical Approaches to Nutrition Support, p vii) and changes in
c. See Table 6-4 (p 118, footnote 3) for approximate packed weight of ProViMin powder in
C. Energy
1. Calculate energy (kcal) provided by fat (Appendix 10, p A-9), beikost, or table foods
(Tables 10-2 and 10-3, pp 203-204) and add to that supplied by ProViMin, skim milk, or other
protein containing foods (Tables 10-2 and 10-3, pp 203-204).
2. Subtract amount of energy supplied by these sources from total energy requirement.
3. Supply any remaining prescribed energy with Polycose ® Glucose Polymers powder
(23 kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9), sugar (48 kcal/Tbsp),
beikost, or table foods containing little or no fat (Tables 10-2 and 10-3, pp 203-204).
4. Add baby foods after infant is 3 to 4 months old to provide variety in taste, color, and texture
(Table 10-2, p 203) if developmentally ready.
D. L-Carnitine (Appendix 28, p A-29)

1. Add liquid L-carnitine to ProViMin medical food mixture.
2. L-carnitine tablets may be used if patient is capable of swallowing them.
E. GLY (Appendix 28, p A-29)
1. Add GLY powder to ProViMin medical food mixture.

1. Boil bottles, nipples, rings and mixing utensils for 5 minutes and cool. Boil more water for
5 minutes and cool to room temperature.
2. Measure or weigh specified amounts of boiled, cooled water, ProViMin, fat, and carbohydrate
into clean containers.
3. Pour 1/2 of specified amount of boiled, cooled water into clean blender. Running blender at
slow speed, gradually add ProViMin and blend mixture for at least 15 seconds.
4. Slowly pour specified amount of fat into blender and continue blending for no longer than 1 to
3 seconds.
5. Dissolve powdered carbohydrate in some of remaining water and pour into ProViMin and fat
mixture, mix well, add water to yield prescribed volume,

6 Refrigerate in sterilized, closed containers until used. Discard unused portion 24 hours after
mixing because of nutrient loss. Shake well before feeding.
7. Do not use microwave oven to warm formula. Unevenly heated formula can burn infants and
steam can make bottles explode.
8. Discard formula remaining in bottle or cup after feeding.
9. Notify parents or caretakers when they may discontinue aseptic technique in making formula.
G. Riboflavin (Appendix 26, p A-28).
1. Should be administered orally with medical food mixture or meal.
2. Add finely crushed tablets to ProViMin medical food mixture.
3. Administer only 25 to 30 mg per time with food since more will not be absorbed (51).
H. Diet Guide
1. Provide parents, caretakers, or patient with completed Diet Guide (Table 10-4, p 205) with
each diet change.
Warning: Never permit infant to fast > 4 hours, child > 6 hours, or adult > 8 hours; less
time if patient is febrile, has diarrhea, or is vomiting.

a. See Table 10-2, p 203, for nutrient composition of ProViMin and skim milk.
b. See Appendix 9, p A-9, for composition of Polycose.
2. Check diet to determine if it supplies Recommended Daily Intakes (RDIs) for minerals and
not available.
b. If ProViMin mixture provides < 100% of RDIs for age, supplement diet with needed
minerals and vitamins if not provided by beikost or table foods and laboratory tests
indicate need (Appendix 11, p A-10, for composition of supplements).
B. Osmolarity
b. Osmolarity per gram of ProViMin powder is 2 mosm.
2. If osmolarity is > 450 mosm/L for neonate (30), > 750 mosm/L for children, > 1,000 mosm/L
for adults, or greater than tolerated by patient, increase water content of prescribed medical
food mixture and recalculate its osmolarity.
renal solute load.
recalculate.

A. Blood Glucose Concentration
1. Measure during febrile episodes. If below normal, increase carbohydrate intake either by oral
feeds or intravenous solutions.

B. Plasma L-Carnitine Concentration
1. Measure plasma free carnitine concentration monthly until patient is 6 months of age and
every 3 to 6 months thereafter.
2. If free carnitine concentration is < 30 µmol/L:
a. Increase prescribed L-carnitine by 5% and reevaluate plasma concentration in 1 month.
b. If concentration continues below normal, repeat above process until value is in normal
range.
C. Protein Status
1. Evaluate plasma transthyretin concentration every 3 months until patient is 1 year old and
twice yearly thereafter (Appendix 17, p A-18, for standards).
2. If plasma transthyretin concentration is below normal for age:
a. Increase prescribed amount of protein by 5% to 10% and reevaluate transthyretin
concentration in 1 month.
normal range.
D. Urine Organic Acids
1. Evaluate monthly in infancy and every 2 to 3 months in children and adults.
2. If present and patient is not ill, decrease fat in diet by 3% to 5% and protein by 1% to 2%.
3. If fat is decreased to < 15% of energy, supplying adequate linoleic and α-linolenic acids may
become difficult.
E. Iron Status
b. If plasma ferritin concentration is below normal for age:
2) Evaluate plasma ferritin concentration monthly.
F. Growth Status
a. Measure monthly to 1 year, every 3 months to 4 years, and twice yearly thereafter. Plot
infants and children will fall above or below these percentiles. Maintain appropriate weight
for height in adults.
2. If infant's or child's length/height or weight falls below usual growth channel:
achieved.
G. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of fat, linoleic and α-linolenic acids, protein, energy, minerals, and vitamins
after each diet change.
not available.
H. Clinical Summary
A. Example
Establish and fill prescription for newborn weighing 3.5 kg using Recommended Daily Nutrient Intakes
from Table 10-1, p 203, and nutrient contents from Tables 10-2 and 10-3, pp 203 and 204, and
Appendix 10, p A-9.
Fat 420 kcal x 0.20 = 84 kcal ÷ 9 kcal = 9.3 g
Protein 3.5 kg x 2.0 g/kg = 7.0 g
Carbohydrate 420 kcal - 112 kcal = 308 kcal ÷ 4 kcal = 77 g
Medical Food Mixture Measure Fat Protein Energy
(g) (g) (kcal)
ProViMin 9.6 g 0.13 7.00 30
Soy Oil 10.0 mL 9.00 0.00 80
Polycose powder 82 g 0.00 0.00 312
Total per day 9.13 7.0 422

Percentage of energy as fat 20%
load is < 65 mosm.
Linoleic acid is 4.60 g or 9.8% of energy; α-linolenic acid is 0.70 g or 1.49% of energy.

A. Rationale
1. In normal persons, febrile illness and trauma are accompanied by catabolism of body fat and
protein (47).
2. Well-nourished patients with GA-II respond to infection and trauma as do normal persons.
2. Depress catabolism
Jell-O ®; Polycose powder or liquid (Appendix 9, p A-9) added to fruit juices or Pedialyte if
tolerated; and caffeine-free soft drinks (not diet drinks).
b. Add 1/3 cup Polycose powder to Pedialyte liquid to yield 8 fl oz.
c. Return patient to ProViMin medical food mixture as rapidly as possible.
1) Begin with 1/2 original strength ProViMin medical food mixture.
d. Feed Polycose solution (5 to 7 g carbohydrate/kg) or carbohydrate-containing foods every
2 to 3 hours.
1) If unable to feed every 2 to 3 hours, administer solution of raw cornstarch (2 to 3 g/kg)
to children older than 9 months.
e. Administer 10% glucose solution intravenously if oral intake cannot be maintained.
3. Prevent low blood glucose concentrations.
4. Prevent accumulation of toxic fatty acids.
a. Add liquid L-carnitine to Pedialyte.
Warning: Intravenous administration of lipids is contraindicated.

TABLE 10-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With Glutaric
Acidemia Type II
Age Nutrient
1
Protein Fat Energy1 Fluid2
(g/kg) (% of energy) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 2.0 - 1.7 20 - 25 120 (145 - 95) 150 - 125
3 to < 6 mo 1.7 - 1.4 20 - 25 115 (145 - 95) 160 - 130
6 to < 9 mo 1.4 - 1.1 20 - 25 110 (135 - 80) 145 - 125
9 to < 12 mo 1.4 - 1.1 20 - 25 105 (135 - 80) 135 - 120
(g/day) (% of energy) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 15 - 23 20 - 25 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 20 - 30 20 - 25 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 25 - 34 20 - 25 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 30 - 40 20 - 25 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 40 - 45 20 - 25 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr 45 - 50 20 - 25 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 40 - 42 20 - 25 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 42 - 49 20 - 25 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr 49 - 55 20 - 25 2,900 (2000 - 3300) 2,000 - 3,300
1 Modified from reference 12.
2 Modified from reference 2. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid
TABLE 10-2. Average Nutrient Contents of Gerber ® Baby Foods, ProViMin, and Skim Milk 1
Food Measure Fat Protein Energy

(g) (g) (kcal)
Cereals, Dry, Ready To Serve 1 Tbsp2 0.17 0.25 15
Cereals with Fruit, 2nd ® and 3rd Foods ®, Jarred 1 Tbsp2 0.07 0.16 11
Desserts, 2nd ® and 3rd Foods ® 1 Tbsp2 0.04 0.10 12
Desserts, Tropical Fruit 1 Tbsp2 0.00 0.01 10
2
Fruits, 1st ®, 2nd ®, and 3rd Foods ® 1 Tbsp 0.00 0.10 10
Dices 1 jar 0.00 1.00 62
Juices 1 fl oz 0.00 0.07 16
Meats 2nd ® and 3rd Foods ® 1 Tbsp2 0.67 1.58 14
2
Vegetables, 1st ®, 2nd ®, and 3rd Foods ® 1 Tbsp 0.04 0.19 6
Vegetable Dices 1 jar 0.00 1.00 25
3
Milk, Skim 100 mL 0.19 3.53 36
ProViMin ® 100 g 1.40 73.00 312
1
Nutrient Values. Fremont, Michigan: Gerber Products Co, 2000.
2
US standard level measure.
3
From reference 36.

TABLE 10-3. Exchange Lists for Nutrition Support of Children and Adults With Glutaric Acidemia Type II1
Food List Measure Fat Carbohydrate Protein Energy

(g) (g) (g) (kcal)
Meat, lean 1 oz 3 0 7 55
Milk, skim 1 cup trace 12 8 86
Fat2 varies 5 0 0 45
Fruit 1/2 cup canned or 1/2 cup fresh or juice 0 20 0 60
1/2 cup dried 0 15 0 80
Starch/Bread varies trace 15 3 25
Vegetable 1/2 cup cooked, or 1 cup raw 0 5 2 25
1
Exchange Lists for Weight Maintenance. Chicago: The American Dietetic Association, 1995.
2
Care must be taken to select fats that provide adequate linoleic and α-linolenic acids, such as soy or canola oil.

TABLE 10-4. Glutaric Acidemia Type II Diet Guide
Date: ______ ___ _/______ ____/__________ Hospital Number:

Mo Day Year
Name:_________________________________________________________________________________
Birth Date: ______ ___ _/______ ____/__________ Age:

Mo Day Year
Length/Height: ____________________ (cm/in) Weight: ______________________ (kg/lb)
Medical Food Amount Protein Fat Energy

(g) (g) (kcal)
ProViMin g
mL
mL
Skim milk cups
Add water to make ________________________ mL ________________ (fl oz)
Beikost or table foods Tbsp/Exchanges
Cereals/Starch/Bread
Cereals: With Fruit
Desserts
Fruits/Juices
Meats, lean
Vegetables
Total per day
Total per kg
Percentage of energy
Comments:
____________________________________________________
Nutritionist

206 Glutaric Acidemia Type II
TABLE 10-5. Glutaric Acidemia Type II Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

Length/ Weight Head Plasma Carnitine Blood Ferritin Trans- Hgb Blood Fat Linoleic Linolenic Protein L- Glycine Energy
Height Circum Glucose thyretin Ammonia Acid Acid Carnitine
Free Total
(mo/d/yr) (cm) (kg) (cm) (µmol/L) (µmol/L) (mg/dL) (ng/mL) (mg/dL) (g/dL) (µmol/L) (g) (%) (g) (%) (g) (%) (g) (mg) (mg) (kcal)
REFERENCES
Dis 2000;23 Suppl 1:29A.
1996.
3. Bell RB, Brownell AKW, Roe CR, et al: Electron transfer flavoprotein: Ubiquinone oxidoreductase (ETF:QO)
deficiency in an adult. Neurology 1990;40:1779-1782.
4. Bennett MJ, Curnock DA, Engel PC, et al: Glutaric aciduria type II: Biochemical investigation and treatment of a
child diagnosed prenatally. J Inher Metab Dis 1984;7:57-61.
5. Böhm N, Vy J, Kiessling M, Lehnert W: Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II),
congenital polycystic kidneys, and symmetric warty dysplasia of the cerebral cortex in two newborn brothers.
II. Morphology and pathogenesis. Eur J Pediatr 1982;139:60-65.
6. Bone J, Chalmers RA, Tracey BM, et al: Prenatal diagnosis of dysmorphic neonatal-lethal type II glutaric aciduria.
Lancet 1984;1:846-847.
7. Brivet M, Tardieu M, Khellaf A, et al: Riboflavin responsive ethylmalonic-adipic aciduria in a 9-month-old boy with
liver cirrhosis, myopathy, and encephalopathy. J Inher Metab Dis 1991;14:333-337.
8. Colevas AD, Edwards JL, Hruban RH, et al: Glutaric acidemia type II. Comparison of pathologic features in two
infants. Arch Pathol Lab Med 1988;112:1133-1139.
9. de Visser M, Scholte HR, Schutgens PA, et al: Riboflavin-responsive lipid-storage myopathy and glutaric aciduria
type II of early adult onset. Neurology 1986;36:367-372.
10. Di Donato, Frerman FE, Rimoldi M, et al: Systemic carnitine deficiency due to lack of electron transfer
flavoprotein:ubiquinone oxidoreductase. Neurology 1986;957-963.
11. Dusheiko G, Kew MC, Joffe BI, et al: Recurrent hypoglycemia associated with glutaric aciduria type II in an adult.
New Engl J Med 1979;301:1405-1409.
Washington DC: National Academy of Sciences, 1980 and 1989.
13. Frerman FE, Goodman SI: Defects of electron transfer flavoprotein and electron transfer flavoprotein - ubiquinone
oxidoreductase: Glutaric aciduria type II, ed 8. New York: McGraw-Hill Medical Publishing Division, 2001, pp
2357-2366.
14. Galloway JH, Cartwright IJ, Bennett MJ: Abnormal myocardial lipid composition in an infant with type II glutaric
aciduria. J Lipid Res 1987;28:279-284.
15. Goodman SI, Frerman FE: Glutaric acidaemia type II (multiple acyl-CoA dehydrogenation deficiency). J Inher
Metab Dis 1984;7(suppl 1):33-37.
16. Goodman SI, Reale M, Berlow S: Glutaric acidemia type II: A form with deleterious intrauterine effects. J Pediatr
1983;102:411-413.
17. Goodman SI, Stene DO, McCabe ERB, et al: Glutaric acidemia type II: Clinical, biochemical, and morphologic
considerations. J Pediatr 1982;100:946-950.
18. Green A, Preece MA, De Sousa C, Pollitt RJ: Possible deleterious effect of L-carnitine supplementation in a patient
with mild multiple acyl-CoA dehydrogenation deficiency (ethylmalonic-adipic aciduria). J Inher Metab Dis
1991;14:691-697.
19. Gregersen N, Christensen MF, Christensen E, Kølvraa S: Riboflavin responsive multiple acyl-CoA
dehydrogenation deficiency. Assessment of 3 years of riboflavin treatment. Acta Paediatr Scand 1986;75:676-
681.
20. Gregersen N, Kølvraa S, Rasmussen K, et al: Biochemical studies in a patient with defects in the metabolism of
acyl-CoA and sarcosine: Another possible case of glutaric aciduria type II. J Inher Metab Dis 1980;3:67-72.
21. Gregersen N, Rhead W, Christensen E: Riboflavin responsive glutaric aciduria type II. In Fatty Acid Oxidation
Defects: Clincal, Biochemical, and Molecular Defects. New York: Alan R Liss, Inc, 1990, pp 477-494.
22. Harpey JP, Charpentier C, Coude M: Methylene-blue for riboflavin-unresponsive glutaric aciduria type II. Lancet
1986;1:391.
23. Harpey JP, Charpentier C, Goodman SI, et al: Multiple acyl-CoA dehydrogenase deficiency occurring in pregnancy
and caused by a defect in riboflavin metabolism in the mother. J Pediatr 1983;103:394-398.
24. Henderson HE, Balla R, De Jong G, et al: Postnatal and antenatal laboratory diagnosis of glutaric aciduria type II
in a South African family. S Afr Med J 1987;71:589-591.
25. Hoffman GF, Hunneman DH, Jakobs C, et al: Progressive fatal pancytopenia, psychomotor retardation, and
muscle carnitine deficiency in a child with ethylmalonic aciduria and ethylmalonic acidaemia. J Inher Metab Dis
1990;13:337-340.
26. Jakobs C, Sweetman L, Wadman SK, et al: Prenatal diagnosis of glutaric aciduria type II by direct chemical
analysis of dicarboxylic acids in amniotic fluid. Eur J Pediatr 1984;141:153-157.
27. Lipshitz F, Moses N: Growth failure: A complication of dietary treatment of hypercholesterolemia. Am J Dis Child
1989;143:537-542.

28. Loehr JP, Goodman SI, Frerman FE: Glutaric acidemia type II: Heterogeneity of clinical and biochemical
phenotypes. Pediatr Res 1990;27:311-315.
1982.
30. Mandel H, Africk D, Blitzer M, Shapira E: The importance of recognizing secondary carnitine deficiency in organic
acidaemias: Case report in glutaric acidaemia type II. J Inher Metab Dis 1988;11:397-402.
31. Mantagos S, Genel M, Tanaka K: Ethyl-malonic-adipic aciduria. J Clin Invest 1979;64:1580-1589.
1987;1:1-17.
33. Mongini T, Doriguzzi C, Palmucci L, et al: Lipid storage myopathy in multiple acyl-CoA dehydrogenase deficiency:
An adult case. Eur Neurol 1992;32:170-176.
34. Mooy PD, Giesberts MA, van Geldersen HH, et al: Glutaric aciduria type II: Multiple defects in isolated muscle
mitochondria and deficient ß-oxidation in fibroblasts. J Inher Metab Dis 1984;7(Suppl 2):101-102.
35. Mooy PD, Przyrembel H, Giesberts MA, et al: Glutaric aciduria type II: Treatment with riboflavin, carnitine, and
insulin. J Eur Pediatr 1984;143:92-95.
37. Przyrembel H, Wendel V, Becker K, et al: Glutaric aciduria type II: Report on a previously undescribed metabolic
disorder. Clin Chim Acta 1976;66:227-239.
38. Rinaldo P, Welch RD, Previs SF, et al: Ethylmalonic/adipic aciduria: Effects of oral medium-chain-triglycerides,
carnitine, and glycine on urinary excretion of organic acids, acylcarnitines, and acylglycines. Pediatr Res
1991;30:216-221.
39. Sakuma T, Sugiyama N, Ichiki T, et al: Analysis of acylcarnitines in maternal urine for prenatal diagnosis of
glutaric aciduria type 2. Prenat Diagn 1991;11:77-82.
41. Smith CA, Nelson NM: The Physiology of the Newborn Infant, ed 4. Springfield, IL: Charles C Thomas Publisher,
1976.
1989;143:828-832.
43. Sweetman L, Nyhan WL, Trauner DA, et al: Glutaric aciduria type II. J Pediatr 1980;96:1020-1026.
44. Tanaka K, Mantagos S, Genel M, et al: New defect in fatty-acid metabolism with hypoglycaemia and organic
aciduria. Lancet 1977;2:986-987.
45. Turnbull TM, Bartlett K, Eyre JA, et al: Lipid storage myopathy due to glutaric aciduria type II: Treatment of a
potentially fatal myopathy. Dev Med Child Neurol 1988;30:667-672.
46. Uziel G, Garavaglia B, Ciceri E, et al: Riboflavin-responsive glutaric aciduria type II presenting as a
leukodystrophy. Pediatr Neurol 1995;13:333-335.
1977;30:1269-1280.
48. Warshaw JB, Curry E: Comparison of serum carnitine and ketone body concentrations in breast- and in formula-
fed newborn infants. J Pediatr 1980;97:122-125.
49. Yamaguchi S, Orii T, Maeda K, et al: A new variant of glutaric aciduria type II: Deficiency of α-subunit of electron
transfer flavoprotein. J Inher Metab Dis 1991;13:783-786.
50. Yamaguchi S, Orii T, Suzuki Y, et al: Newly identified forms of electron transfer flavoprotein deficiency in two
patients with glutaric aciduria type II. Pediatr Res 1992;29:60-63.
51. Zempleni J, Galloway JR, McCormick DB: Pharmokinetics of orally and intravenously administered riboflavin in
healthy humans. Am J Clin Nutr 1996;63:54-66.

PROTOCOL 11 — Lysinuric Protein Intolerance

PRO-PHREE ® Protein-Free Energy Module With Iron, Vitamins & Minerals
I. Introduction
Lysinuric protein intolerance (LPI) results from an autosomal recessive defect in intestinal, hepatic, and
renal transport of the dibasic (cationic) amino acids lysine (LYS), arginine (ARG), and ornithine
(ORN). Decreased intestinal and renal tubular reabsorption of these amino acids results in depressed
plasma concentrations (Figure J). The depleted pools of ARG and ORN impair hepatic urea cycle
function causing hyperammonemia (7, 30). Hyperammonemia and growth retardation are the earliest
manifestations of LPI (2, 29, 30). Patients with LPI present with failure to thrive, protein intolerance,
osteoporosis, hepatomegaly, muscle hypotonia, and hematologic abnormalities (30). Seizures and
mental retardation have also been reported (29); but most patients have normal cognitive abilities.
Thymic hypoplasia has been described in one patient (9). Compromised humoral immune responses
(14) and intermittent hematophagocytic lymphohistiocytosis has been reported in patients with LPI (4).
Genetic defect of epithelial LYS, ARG, and ORN transport
Decreased Decreased Decreased

intestinal absorption tubular reabsorption transport into liver cells
Deficiency of LYS, ARG, and ORN
Protein Impaired
malnutrition urea cycle
Postprandial
hyperammonemia
Growth failure Nausea
Osteoporosis Protein aversion
Hepatomegaly Seizures
Stupor
Coma
Figure J. Metabolic and clinical effects of decreased LYS, ARG, and ORN transport (modified
from reference 30)

Long-term LYS deficiency may contribute to osteoporosis, and delayed skeletal maturation (2, 21, 33).
The use of oral L-citrulline (CIT) and a protein-restricted diet resulted in improved protein tolerance,
corrected hyperammonemia, accelerated growth, and increased bone mass (2, 7, 17). L-ARG
supplements have also been used with moderate clinical success, but intestinal absorption is poor.
Acute and chronic pulmonary involvement may progress to alveolar proteinosis (granular
proteinaceous material in alveoli) or cholesterol granulomas resulting in poor outcome. Death
secondary to pulmonary complications has been reported in several pediatric patients (11). Early
diagnosis and aggressive nutrition support improve the outcome in patients with LPI. Successful
reproductive outcome of a woman with LPI has been reported (34).
212 Lysinuric Protein Intolerance © 2001 Ross Products Division

A. The Defect
1. LPI results from defect in renal, intestinal, and hepatic membrane transport of dibasic amino
acids, LYS, ARG, and ORN (30).
© 2001 Ross Products Division Lysinuric Protein Intolerance 213

1. Diagnostic studies should be considered for any infant or child who presents with following
clinical symptoms:
a. Vomiting, poor appetite, failure to thrive.
b. Protein/energy malnutrition (2, 18, 20, 29)
c. Hepatosplenomegaly.
d. Hypotonia.
e. Skeletal abnormalities (2, 7, 21, 33)
f. Acute or chronic interstitial lung disease and pulmonary cholesterol granulomas (11, 20,
30).
g. Renal tubular disease (3).
2. Biochemical findings (29, 30).
a. Subnormal to low normal plasma concentrations of LYS, ARG, and ORN.
b. Excessive urinary excretion of LYS, ARG, and orotic acid (23, 24, 25).
c. Subnormal argininosuccinate synthetase activity (19).
d. Homocitrullinuria and homoargininuria (10).
e. Elevated plasma ferritin (27) and thyroxin-binding globulin (30).
f. Hyperammonemia (100-560 µmol/L postprandial) (8).
g. Abnormal immune function (14, 36).

1. Restrict dietary protein to amount tolerated without hyperammonemia.
B. Provide Alternate Metabolic Pathways
1. Prescribe L-CIT to correct deficiency of urea cycle intermediates (ARG and ORN), help
normalize plasma ammonia concentration (17, 28), improve protein tolerance (30), and
promote normal growth and development.
C. Supplement Essential Nutrient
1. Long-term oral LYS supplements have not been successful in increasing plasma LYS
concentrations (26, 29). Short-term oral and intravenous LYS supplementation has normalized
plasma LYS concentration (12, 13).
2. N-acetyllysine, a readily absorbable form of LYS, has been used only in acute situations (26).

1. Maintain 2- to 4-hour postprandial plasma amino acid concentrations in following ranges or
within normal range for age established by laboratory used:
Amino acid µmol/L
Alanine (ALA) (19) 148 - 485
ARG (10, 24, 25) 57 - 142
CIT (19, 28, 29) 20 - 55
Glycine (GLY) (29) 117 - 223
LYS (2, 26, 28) 85 - 218
ORN (2, 24, 29) 26 - 96
Serine (SER) (29) 79 - 112
standards should be developed if plasma amino acids are evaluated at other times.
B. Plasma Ammonia Concentration
1. Maintain plasma ammonia concentration < 35 µmol/L (0.06 mg/dL) or in normal range for age
as established in laboratory used.
1. Support normal growth in infants and children and maintain appropriate weight for height in
adults.

a. Prevent catabolism.
b. Prevent ARG and ORN deficiencies.
c. Prevent prolonged fasting.
D. Physical manifestations
1. Inhibit progressive osteoporosis.

A. Protein
1. Prescribe amount that promotes goals of nutrition support (Table 11-1, p 216).
2. Protein may need to be increased if sodium benzoate, sodium phenylacetate, or sodium
phenylbutyrate is administered daily.
Warning: Excessive protein intake will result in acute hyperammonemia. Inadequate
protein intake will result in failure to thrive in infants, and weight loss in
children and adults, low plasma transthyretin concentration, delayed skeletal
maturation, and hair loss.
B. Energy
1. Prescribe amount greater than Recommended Dietary Allowances (RDAs) (6) to prevent
catabolism (Table 11-1, p 216).
2. Requirements vary widely and may be 5% to 10% greater than those listed in Table 11-1,
p 216, when infection or hyperammonemia is present.
Warning: Inadequate energy intake results in poor growth in infants and children;
weight loss in children and adults; decreased dietary protein tolerance; and
increased body protein catabolism, leading to hyperammonemia.
C. L-CIT
1. May be used in place of L-ARG or L-ORN to correct deficient intermediates in urea cycle and
prevent hyperammonemia. L-CIT is readily absorbed from intestine and partly converted to
ARG and ORN (17, 25, 30).
2. Amount prescribed may differ based on age, weight, and tolerance to protein intake.
3. Recommended L-CIT supplementation is as follows:
Age Amount
(g/day)
Infants/Toddlers < 10 kg (3, 28) 2.5 - 4.8
Children >10 kg and Adults (29, 30) 4.8 - 8.0
a. Must be divided into 3 to 5 doses per day and taken with protein-containing meals.
b. Doses must be individually prescribed based on protein intake and extent of
hyperammonemia.
D. Fluid

A. Protein
1. Calculate amount of infant formula, beikost, whole cow’s milk, or table foods (Table 11-2,
2. See Servings Lists for PHE-Restricted Diets (Protocol 1, pp 13-26), for portion sizes.
B. Energy
1. Calculate energy provided by infant formula, beikost, whole cow's milk, or table foods
(Table 11-2, p 216) required to fill protein prescription.

3. Provide remaining prescribed energy with Pro-Phree ® Protein-Free Energy Module with Iron,
Vitamins & Minerals (Appendix 11, p A-10), sugar (48 kcal/Tbsp), or Free Foods B
(Table 11-2, p 216).
a. For infants and toddlers, Pro-Phree is recommended choice for energy.
b. Do not use corn syrup for infants because of osmolarity it yields (16).
c. Do not use honey for infants because it may contain botulinum toxin (32).
Note: Due to chronic elevated plasma ferritin concentrations in patients with LPI, it
may be beneficial to use low-iron infant formula.
C. L-CIT (Appendix 26, p A-28)
1. Solution of L-CIT.
a. Mix weighed amount of L-CIT powder with boiled, cooled water to yield 100 mg/mL
(eg, 100 g L-CIT with enough water to yield 1 liter). Make enough solution to last 1 week.
b. Refrigerate in sterilized, closed container until used. Discard unused suspension after
c. Shake well before using. Measure L-CIT solution into medical food mixture using
disposable syringe.
2. For children and adults, L-CIT may be added to beverages offered at each protein-containing
meal.
3. L-CIT powder may be given in pre-weighed capsules (29).
1. Add sufficient boiled, cooled water to infant formula, L-CIT solution and Pro-Phree to yield
prescribed volume. Tap water may replace boiled, cooled water when preparing medical food
mixture for older infants, children, and adults.
2. Mix with sterilized blender at lowest speed for no longer than 3 seconds. Excess mixing may
destabilize emulsion. May also be mixed in sterilized, tightly closed container by shaking
can burn infants and steam can make bottles explode.
E. Diet Guide
1. Provide parents, caregivers, or patient with completed Diet Guide (Appendix 22, p A-24) with
each diet change.

formulas, Appendix 8, A-8, for composition of whole cow's milk, and Appendix 11, p A-10,
for compostion of Pro-Phree.
not available.
c. If infant formula plus Pro-Phree mixture provides < 100% of RDIs for age, supplement
diet with needed minerals and vitamins if not provided by beikost or table foods and
laboratory tests indicate need (Appendix 11, p A-10, for composition of supplements).

B. Osmolarity
b. Osmolarity per gram of Pro-Phree, Similac, Isomil, and whole cow's milk is listed in
2. If osmolarity is > 450 mosm/L for infants (15), > 750 mosm/L for children, > 1,000 mosm/L for
renal solute load.
recalculate.

A. Plasma ARG, LYS, AND ORN Concentrations
1. Initial.
a. Evaluate twice weekly by quantitative methods until plasma concentrations stabilize.
2. Ongoing.
b. Evaluate at least monthly when patient's condition is stable. For infants, evaluate every
2 weeks to 1 month.
3. Unacceptable plasma ARG, LYS, and ORN concentrations.
a. Plasma LYS concentrations usually remain chronically low despite nutrition support (29).
b. If plasma ARG or ORN concentrations are below lower limit of normal and patient has
ingested and tolerated full protein prescription:
1) Either increase prescribed amount of protein or L-CIT supplementation by 5% to 10%
and reevaluate plasma concentrations in 3 to 7 days.
2) If any amino acid continues below lower limit of normal, repeat above process until
value is in treatment range listed.
Warning: Plasma ARG or ORN deficiency will result in hyperammonemia (30, 37).
B. Blood Ammonia Concentration
1. Initial.
a. Evaluate daily until concentration is in normal range (< 35 µmol/L).
2. Ongoing.
a. Evaluate weekly until patient is 6 months old, twice monthly until 12 months of age, and
monthly thereafter if patient is stable and well.
3. Elevated blood ammonia concentration.
a. Obtain 3-day diet diary and evaluate protein intake.
b. Evaluate patient for infection.
c. If infection is ruled out, protein intake is not greater than prescribed, and energy intake is
not less than prescribed:
1) Increase L-CIT supplement by 10% and reevaluate blood ammonia and plasma ARG
and ORN concentrations in 2 to 3 days.
Warning: Blood ammonia concentration is strongly correlated with protein ingestion
and below-normal plasma ARG and ORN concentrations.
2) If blood ammonia concentration remains above upper limit of normal, repeat above
process until normal concentration is attained.

C. Protein Status
1. Evaluate plasma transthyretin concentration every 3 months throughout life (Appendix 17,
concentrations show a clear deficiency.
2. If plasma transthyretin concentration is below normal:
a. Increase prescribed protein by 5% to 10%, if tolerated, and reevaluate plasma
transthyretin concentration in 1 month.
b. If plasma transthyretin concentration continues below standard, repeat above process as
tolerated until value is in normal range.
c. Evaluate blood ammonia concentration with each increase in prescribed protein.
D. Iron Status
b. Plasma ferritin concentrations are chronically elevated in patients with LPI secondary to
LYS deficiency (27, 30).
E. Complete blood count and differential
1. Hemoglobin and hematocrit concentrations and differential should be evaluated at 6, 9, and
12 months of age and every 6 months thereafter (Appendix 17, p A-18, for standards).
F. Growth Status
a. Measure monthly to 1 year, every 3 months thereafter until physical growth is completed,
and every 6 months thereafter. Plot measurements on NCHS growth charts.
a. Evaluate plasma LYS, ARG, ORN, and blood ammonia concentrations. If blood ammonia
concentration is normal and plasma LYS, ARG, and ORN concentrations are low or below
normal, increase prescribed protein and energy by 5% and remeasure in 1 month.
b. If length/height and weight remain low, repeat above process until usual growth channel is
achieved.
c. Evaluate blood ammonia and plasma LYS, ARG, and ORN concentrations within 4 days
to 1 week after each increase in prescribed protein.
G. Nutrient Intake
and 25, pp A-16 and A-27).
2. Evaluate intakes of protein and energy before each blood test.
not available.
H. Clinical Summary
management (Table 11-3, p 217)
A. Establish and fill diet prescription for 4-month-old male weighing 6.2 kg using Recommended
Daily Nutrient Intakes from Table 11-1, p 216, and nutrient contents from Table 11-2, p 216.

1. Establish prescription:
L-CIT = 4.0 g
Protein 2.0 g/kg x 6.2 kg = 12.4 g/day
Energy 130 kcal/kg x 6.2 kg = 806 kcal/day
Fluid 150 mL/kg x 6.2 kg = 930 mL/day
2. Fill prescription:
Medical Food Mixture Measure L-CIT Protein Energy
(g) (g) (kcal)
Similac with Iron Ready to Feed 886 mL --- 12.4 602
L-CIT solution1 40.0 mL 4.0 --- ---
Pro-Phree 40 g --- 0.0 204
Add water to make 930 mL (31 fl oz)

Total per kg --- 2.0 130
Approximate osmolarity of medical food mixture is 375 mosm/L. Estimated renal solute load is
< 150 mosm.
1
L-CIT should be given in doses of 1.0 g/10 mL 4 times per day.
B. Establish and fill diet prescription for 6-year-old girl weighing 20 kg using Recommended Daily
Nutrient Intakes from Table 11-1, p 216, and nutrient contents from Table 11-2, p 216.
L-CIT 6.0 g
Protein 20 g protein
Energy 2000 kcal
Fluid 2000 mL
Milk Substitute Mixture Measure L-CIT Protein Energy
(g) (g) (kcal)
Whole milk 236 mL --- 8.0 149
L-CIT solution1 60 mL 6.0 0.0 0
Pro-Phree 90 g --- 0.0 459
Add water to make 710 mL (24 fl oz). Offer additional fluid ad libitum daily
Food List Servings

Bread/cereal 10 --- 6.0 300
Fats 4 --- 0.4 240
Fruits 5 --- 2.5 300
Vegetables 6 --- 3.0 60
Free Foods A 5 -- 0.5 325
Free Foods B 3 --- 0.0 165
Total per day 6.0 20.4 1,998
1
L-CIT should be given as 1.5 g/ 15 mL 4 times daily.
XI. Nutrition Support During Febrile Illness or Following Trauma Associated with Acute
Hyperammonemia
A. Rationale
protein (35).
2. Well-nourished patients with LPI respond to infection and trauma as do normal persons (29).
Warning: Prolonged use of protein-free (> 2 days) or low-energy diet will lead to protein
catabolism and rebound hyperammonemia.
3. Intravenous infusion of ORN, ARG, or CIT to correct for hyperammonemia has been
suggested (30).

TABLE 11-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults with Lysinuric
Protein Intolerance
Age Nutrient
Protein 1-3 Energy2 Fluid4
(g/kg) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 2.20 - 1.5 140 - 125 160 - 130
3 to < 6 mo 2.00 - 1.5 130 - 120 160 - 130
6 to < 9 mo 1.80 - 1.25 130 - 115 150 - 125
9 to < 12 mo 1.60 - 1.15 120 - 110 130 - 120
Girls and Boys (g/day) (kcal/day) (mL/day)

1 to < 4 yr 10 - 13 945 - 1,890 945 - 1,890
4 to < 7 yr 14 - 20 1,365 - 2,415 1,365 - 2,445
7 to < 11 yr 20 - 28 1,730 - 3,465 1,730 - 3,465
Women
11 to < 15 yr 30 - 40 1,575 - 3,150 1,575 - 3,150
15 to < 19 yr 40 - 45 1,260 - 3,150 1,260 - 3,150
> 19 yr 45 - 47 1,785 - 2,625 1,875 - 2,525
Men
11 to < 15 yr 30 - 42 2,100 - 3,885 2,100 - 3,885
15 to < 19 yr 42 - 49 2,200 - 4,095 2,200 - 4,095
> 19 yr 49 - 55 2,625 - 3,465 2,625 - 3,465
1
2
3
Protein intake may need to be increased if sodium benzoate, sodium phenylacetate, or sodium phenylbutyrate is
prescribed.
4
TABLE 11- 2. Serving Lists for Protein-Restricted Diets: Approximate Protein And Energy Content Per
Serving
Food List Nutrient

Protein Energy
(g) (kcal)
Breads/cereals 0.6 30
Fats 0.1 60
Fruits 0.5 60
Vegetables 0.5 10
Free Foods A 0.1 65
Free Foods B 0.0 55
1
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 1.86 68
1
Isomil ® Soy Formula With Iron, Ready to Feed, 100 mL 1.66 68
Pro-Phree Protein-Free Energy Module With Iron, Vitamins & Minerals Powder, 100 g 0.00 510
1
Similac With Iron Infant Formula, Ready to Feed, 100 mL 1.40 68
2
Whole cow's milk, 100 mL 3.39 63
1
2
From reference 22. See Appendix 8, A-8, for complete nutrient composition.

TABLE 11-3. Lysinuric Protein Intolerance Clinical Summary Sheet
Date of Birth: __________/__________/__________ Age at Diagnosis:

Mo Day Year
Date Age Physical data Laboratory Data Nutrient Intake Data

Length/ Weight Head LYS ARG ORN L-CIT SGOT SGPT Ammonia HCT Ferritin Trans- CIT Protein Energy
Height Circum thyretin
(mo/yr) (yr/mo) (cm) (kg) (cm) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (U/L) (U/L) (µmol/L) (%) (ng/mL) (mg/dL) (mg) (g) (kcal)
Lysinuric Protein Intolerance 217
REFERENCES
1996.
2. Carpenter TO, Levy HL, Holtrap ME, et al: Lysinuric protein intolerance presenting as childhood osteoporosis.
N Engl J Med 1985;312:290-294
3. DiRocco M, Garibatto G, Rossi GA, et al: Role of haematological, pulmonary and renal complications in the long-
term progress of patients with lysinuric protein intolerance. Eur J Pediatr 1992;152:437-440.
4. Duval M, Fenneteau O, Doireau V, et al: Intermittent hematophagocytic lymphohistiocytosis is a regular feature of
lysinuric protein intolerance. J Pediatr 1999;134:236-239.
1985.
7. Goto I, Yashimura T, Kuroiwa Y: Growth hormone studies in lysinuric protein intolerance. Eur J Pediatr
1984;141:240-242.
8. Kato T, Mizutani N, Ban M: Hyperammonemia in lysinuric protein intolerance. Pediatrics 1984;73:489-492.
9. Hasanoglu A, Dílek EO, Menis, L, Biberglu G: Lysinuric protein intolerance with thymic hypoplasia. J Inher Metab
Dis 1996;19:372-373.
10. Kato T, Sano M, Mizutani N: Homocitrullinuria and homoargininuria in lysinuric protein intolerance. J Inher Metab
Dis 1989;12:157-161.
11. Kerem E, Elpele ON, Shalev RS, et al: Lysinuric protein intolerance with chronic interstitial lung disease and
pulmonary cholesterol granulomas at onset. J Pediatr 1993;123:275-278.
12. Lukkarinen M, Näntö-Salonen K, Pulkki K, et al: Short-term lysine supplementation in lysinuric protein intolerance
(LPI). J Inher Metab Dis 1996;19 (Suppl 1): P97 (abs).
13. Lukkarinen M, Näntö-Salonen K, Pulkki K, et al: Effect of lysine infusion on urea cycle in lysinuric protein
intolerance. Metabolism 2000;49;621-625.
14. Lukkarinen M, Parto K, Ruuskanen O, et al: B and T cell immunity in patients with lysinuric protein intolerance.
Clin Exp Immunol 1999;116;430:434.
1982.
1987;1:1-17.
17. Mizutani N, Kato T, Machara M, et al: Oral administration of arginine and citrulline in the treatment of lysinuric
protein intolerance. Tohoku J Exp Med 1984;142;15-24.
18. Nagata M, Suzuki M, Kawamura G, et al: Immunological abnormalities in a patient with lysinuric protein
intolerance. Eur J Pediatr 1987;146:427-428.
19. Ono N, Kishida K, Tokumoto K, et al: Lysinuric protein intolerance presenting deficiency of argininosuccinate
synthetase. Intern Med 1992;31:55-59.
20. Parto K, Maki J, Pelliniemi LJ, et al: Abnormal pulmonary macrophages in lysinuric protein intolerance.
Ultrastructrural, morphometric and X-ray microanalytic study. Arch Pathol Lab Med 1994;118:536-541.
21. Parto K, Pentliner R, Paronen I, et al: Osteoporosis in lysinuric protein intolerance. J Inher Metab Dis 1993;16:441-
450.
22. Posati LP, Orr ML: Composition of Foods: Dairy and Egg Products, Agricultural Handbook No. 8-1.
Washington, DC: US Dept of Agriculture, Agricultural Research Service, 1976.
23. Rajantie J: Orotic aciduria in lysinuric protein intolerance: Dependence on the urea cycle intermediates. Pediatr
Res 1981;75:115-119.
24. Rajantie J, Simell O, Perheentupa J: Basolateral-membrane transport defect for lysinuric protein intolerance.
Lancet 1980;June 7:1219-1221.
25. Rajantie J, Simell O, Perheentupa J: Intestinal absorption in lysinuric protein intolerance: Impaired for diamino
acids, normal for citrulline. Gut 1980;21:519-524.
26. Rajantie J, Simell O, Perheentupa J: Oral administration of N-acetyl-lysine and homocitrulline in lysinuric protein
intolerance. J Pediatr 1983;102:388-390.
27. Rajantie J, Simell O, Perheentupa J, Siimes MA: Changes in peripheral blood cells and serum ferritin in lysinuric
protein intolerance. Acta Paediatr Scand 1980;69:741-745.
28. Rajantie J, Simell O, Rapola J, Perheentupa J: Lysinuric protein intolerance: A two-year trial of dietary
supplementation therapy with citrulline and lysine. J Pediatr 1980;97:927-932.
29. Simell O: Lysinuric protein intolerance and other cationic amino acidurias. In Scriver CR, et al (eds): The Metabolic
and Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing Division, 2001, pp
4933-4956.

30. Simell O, Parto K, Näntö-Salonen K: Transport defects of amino acids of the cell membrane: Cystinuria, Hartnup
disease, and lysinuric protein intolerance. In Fernandes J, et al (eds): Inborn Metabolic Diseases: Diagnosis and
Treament, ed 3. New York: Springer, 2000, pp 266-273.
1983;7:280-288.
1989;143-828-832.
33. Svedstrom E, Parto K, Martinnen M, et al: Skeletal manifestations of lysinuric protein intolerances in a follow-up
study of 29 patients. Skeletal Radiol 1993;22:11-16.
34. Takayama N, Hamada H, Kubo T: Lysinuric protein intolerance in pregnancy: Case report with successful
outcome. Arch Gynecol-Obstet 1995;256(1):49-52.
1977;30;1269-1280.
36. Yoshida Y, Machigashira K, Suehara M, et al: Immunological abnormality in patients with lysinuric protein
intolerance. J Neurol Sci 1995;134:178-182.
37. Zieve L: Conditional deficiencies of ornithine or arginine. J Amer Coll Nutr 1986;5:167-176.

PROTOCOL 12 — Nonketotic Hyperglycinemia

PRO-PHREE ® Protein-Free Energy Module With Iron, Vitamins & Minerals
I. Introduction
Glycine (GLY) is important in metabolism and functions as a methyl donor, a constituent of proteins, an
oxidant, and conjugates with bile acids. Nonketotic hyperglycinemia (NKH) is an autosomal recessive
inborn error of GLY catabolism in which GLY accumulates in all body tissues, most notably the central
nervous system. Patients with NKH have little or no activity of the mitochondrial GLY cleavage
system which catalyzes the major step in GLY catabolism (Figure K). Four genes that code for P-, H-,
T-, and L-proteins, of this multienzyme complex can be affected. Several forms of NKH are described:
neonatal, atypical (presenting later in life) (16), mild (12) and transient. Patients with the neonatal form
of NKH have a defect in the P-protein gene.
Patients with the neonatal phenotype present in the first days of life with vomiting, poor appetite,
lethargy, muscle hypotonia, apnea, and intractable seizures (9), Some infants may present later in
infancy with a milder clinical course. GLY accumulation in the cerebrospinal fluid (CSF) stimulates the
cortex N-methyl-∆-aspartate (NMDA)-type glutamate receptors, modulating their excitatory activity (9).
The focus of therapy has been to inhibit GLY binding to NMDA receptors. Several NMDA antagonists
including strychnine, imipramine, ketamine, diazepam, and dextromethorphan have been used with
varied effects (11, 19, 28, 35, 40). Tryptophan (TRP) therapy has also been used with moderate
success (14, 20). The current restriction on the use of TRP supplementation in the United States limits
this therapeutic approach. One investigator tried peritoneal dialysis, without benefit (2). Another
approach to treatment is to reduce plasma GLY concentrations via sodium benzoate administration
(11, 38, 41) and a low protein diet (25, 37). Some investigators have supplemented the GLY-restricted
diet with one-carbon donors such as methionine, folate, and choline because of the possible
deficiency of one-carbon units in patients with NKH (9, 37). These carbon donors have not ameliored
the clinical symptoms.
Heme
Oxalate
Porphyrin
Creatine
Purines Nucleic acids

Glycine
Phospholipids Serine NH2-CH2-COOH Proteins (e.g., collagen, elastin)
Pyruvate Glutathione
GCS
Bile acid conjugates; other conjugates
Oxaloacetate Alanine Kreb's Acetyl-CoA
Cycle
NH3 + CO2 + methylene tetrahydrofolate
Site of defect in glycine

cleavage system (GCS)
Figure K. Selected metabolic conversions of GLY (Modified from reference 9)

Whether early diagnosis and intervention affect outcome is not known. Thirty percent of patients with
neonatal onset NKH die in the newborn period (9). Most patients who survive experience significant
neurologic damage with intractable seizures (10, 21, 29). Assessing clinical response to treatment is
difficult due to the variable phenotypes associated with this disorder (5). This protocol is designed to
assist the clinician in prescribing an implementing a low protein diet to restrict intake of amino acids
that are used to synthesize GLY. This protocol should be accompanied by pharmacologic therapy.
224 Nonketotic Hyperglycinemia © 2001 Ross Products Division

A. The Defect
1. NKH results from defect in 1 of 4 protein components (ie, P-, H-, T-, or L-protein) of a
multienzyme complex in mitochondrial GLY cleavage system (15, 34). Most patients with
NKH have defect in P-protein (9, 15).
1. Diagnostic studies should be performed on any neonates who present with neurologic
deterioration, neonatal seizures (often myoclonic), flaccidity, lethargy, or coma, especially if
accompanied by hiccups (9, 24).
2. Other clinical findings include:
a. Vomiting, poor appetite.
b. Pin-point pupils (9, 24, 26, 36).
c. Respiratory insufficiency (9, 13).
3. Laboratory findings:
a. Excessive urine, plasma, CSF GLY concentrations (9).
b. CSF: plasma GLY ratio > 0.2 (7, 24, 33, 34).
c. A CSF: plasma GLY ratio > 0.08 is considered diagnostic for NKH (9).
d. Cortical atrophy, hypodensity of myelin when viewed with MRI.
Note: Urine and plasma GLY concentrations are variable and may be normal.
B. Differential diagnosis:
1. Unlike organic acidemias in which plasma GLY concentrations are elevated, patients with
NKH have normal urinary organic acids and absence of ketosis.
2. Prenatal diagnosis is available for at-risk pregnancies (36).

1. Restrict dietary protein to amount required to reduce plasma GLY concentration and support
normal growth.
Warning: Nutrition support should accompany pharmacologic therapy
(eg, dextromethorphan, imipramine, diazepam, sodium benzoate) as part of
total treatment. See references 1, 11, 19, 22, 27, 28, 38, 40, and 41 for
pharmacologic therapy. If medications are used, review possible
drug:nutrient interactions to prevent nutrition-related clinical symptoms.

A. Plasma GLY Concentration
1. Maintain 2- to 4-hour postprandial plasma GLY concentrations between 56 and 323 µmol/L (9,
11, 19, 25, 27) or within normal concentration for laboratory used.
1. Support normal growth rates in infants and children and maintain appropriate weight for height
in adults.
a. Avoid prolonged fasting.
C. Plasma Free Carnitine Concentration
1. Maintain concentration of plasma free carnitine ≥ 30 µmol/L.

A. Protein
1. Prescribe intake that promotes goals of nutrition support (Table 12-1, p 226).
2. Amount of protein may need to be increased if sodium benzoate is administered daily.
© 2001 Ross Products Division Nonketotic Hyperglycinemia 225

Warning: Inadequate protein intake results in failure to thrive in infants, weight loss,
low plasma transthyretin concentration, and hair loss in children and adults.
B. Energy
1. Prescribe amount greater than Recommended Dietary Allowances (RDAs) to prevent
2. Requirements vary widely and may be 5% to 10% greater than those listed when infection is
present.
Warning: Inadequate energy intake will result in poor growth in infants and children,
weight loss in children and adults, and increased body protein catabolism.
3. If patient is severely developmentally disabled, energy requirements may be less than RDAs.
C. L-Carnitine (39)
1. Prescribe amount required to maintain normal plasma free or erythrocyte concentrations.
a. Initiate intake at 50 mg/kg/day and titrate until plasma free carnitine concentration is
≥ 30 µmol/L.
D. Fluid

A. Protein
1. Calculate amount of infant formula with iron (use until 2nd birthday), beikost, whole cow's
milk, or table foods (Table 12-2, p 226) required to fill protein prescription.
2. See Servings Lists for PHE-Restricted Diets (Protocol 1, pp 13-26), for portion sizes.
3. Parents or patients may select any food in prescribed food lists.
B. Energy
3. Provide remaining prescribed energy with Pro-Phree ® Protein-Free Energy Module With Iron,
Vitamins & Minerals (Appendix 11, p A-10), sugar (48 kcal/Tbsp), or Free Foods B (Table 12-
2, p 226).
a. Do not use corn syrup for infants because of osmolarity it yields (18).
C. Fluid and Mixing Instructions
1. Add sufficient boiled, cooled water to infant formula or whole cow's milk (if child is > 2 years of
age) and Pro-Phree to yield prescribed volume. Tap water may replace boiled, cooled water
when preparing medical food mixture for older infants, children, and adults.
2. Mix in sterilized blender at lowest speed for no longer than 3 seconds. Excess mixing may
destabilize emulsion and cause separation. May also be mixed in sterilized, tightly closed
before feeding.
5. Do not warm medical food mixture in microwave oven. Unevenly heated formula can burn
D. Diet Guide
1. Provide parents, caregivers or patient with completed Diet Guide (Appendix 22, p A-24) with
each diet change.

formula and Appendix 11, p A-10, for composition of Pro-Phree.
not available.
c. If medical food mixture provides < 100% of the RDIs for infants and < 75% for children
and adults, supplement diet with needed minerals and vitamins if not provided by beikost
or table foods and laboratory tests indicate need (Appendix 11, p A-10, for composition of
supplements).
d. Greater than 100% of RDI (Appendices 13 and 14, pp A-14 and A-15) is recommended for
pyridoxine and folic acid, both coenzymes in GLY metabolism.
B. Osmolarity
b. Osmolarity per gram of Pro-Phree, Similac, Isomil, and whole cow's milk is listed in
food mixture and recalculate osmolarity.
renal solute load.
b. Upper limit of renal solute load for infants is approximately 1,100 mosm/L (30).
recalculate.

1. Initial.
a. Evaluate twice weekly by quantitative methods until plasma concentrations stabilize in low
normal range.
2. Ongoing.
b Evaluate at least monthly when patient's condition is stable.
3. Unacceptable plasma GLY concentrations.
a. If plasma GLY concentrations are above upper limit of treatment range and patient has
ingested full protein prescription:
1) Decrease prescribed amount of protein by 5% to 10% and reevaluate plasma
concentration in 3 to 7 days.
2) If plasma GLY concentration continues above upper limit of normal, repeat above
Warning: Protein restriction alone will not reduce plasma GLY concentration to normal
range. Do not over-restrict dietary protein, excessive restriction can result in
protein malnutrition and growth failure.

3) Increase sodium benzoate prescription if not at maximal amount and if deemed safe.
B. Protein Status
1. Evaluate plasma transthyretin concentration every 3 months throughout life (Appendix 17,
2. If plasma transthyretin concentration is below normal:
a. Increase prescribed protein by 5% to 10%, if tolerated, and reevaluate plasma
transthyretin concentration in 1 month.
C. Iron Status
D. Plasma Free Carnitine Concentration
1. Plasma free carnitine concentration should be evaluated as necessary to maintain
concentration ≥ 30 µmol/L.
E. Growth Status
a. Measure monthly to 1 year, every 3 months thereafter until physical growth is completed;
obtain weight every 6 months thereafter. Plot measurements on NCHS growth charts.
a. Increase prescribed protein and energy by 5% and remeasure in 1 month.
b. If length/height and weight remain low, repeat process until usual growth channel is
achieved.
F. Nutrient Intake
and 25, pp A-26 and A-27).
not available.
G. Clinical Summary

A. Establish and fill prescription for 4-month-old male weighing 6.2 kg using Recommended Daily
Nutrient Intakes from Table 12-1, p 226, and nutrient composition from Table 12-2, p 226.
Protein 2 g/kg x 6.2 kg = 12.4 g/day
Energy 130 kcal/kg x 6.2 kg = 806 kcal/day
Fluid 150 mL/kg x 6.2 kg = 930 mL/day
Medical Food Mixture Measure Protein Energy
(g) (kcal)
Similac ® with Iron Ready to Feed 886 mL 12.4 602
Pro-Phree ® 41 g 0.0 209
Total per day 12.4 811

Total per kg 2.0 131
load is < 150 mosm.
B. Establish and fill diet prescription for 6-year old girl weighing 20 kg using Recommended Daily
Nutrient Intakes from Table 12-1, p 226, and nutrient composition from Table 12-2, p 226, and
1. Establish prescription
Protein = 20 g protein
Energy = 2,000 kcal
Fluid = 2,000 mL
2. Fill prescription
(g) (kcal)
Whole cow's milk 236 mL 8.0 146
Pro-Phree ® 91 g 0.0 464
Food List Servings

Bread/cereal 10 6.0 300
Fats 4 0.4 240
Fruits 5 2.5 300
Vegetables 6 3.0 60
Free Foods A 5 0.5 325
Free Foods B 3 0.0 165
Total per day 20.4 2,000
XI. Nutrition Support During Febrile Illness

A. Rationale
1. In normal persons and persons with NKH, febrile illness and trauma are accompanied by
catabolism of body protein (39).
2. Remove protein from diet for 1 or 2 days during febrile illness.
a. See references 9, 11, and 25 for management during acute crises.
Warning: Prolonged use of a protein-free (> 2 days) or low-energy diet will lead to body
protein catabolism.

TABLE 12-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults with
Nonketotic Hyperglycinemia
Age Nutrient
1-3
Protein Energy2 Fluid4
Infants
0 to < 3 mo 2.20 - 1.5 140 - 125 160 - 130
3 to < 6 mo 2.00 - 1.5 130 - 120 160 - 130
6 to < 9 mo 1.80 - 1.25 130 - 115 150 - 125
9 to < 12 mo 1.60 - 1.15 120 - 110 130 - 120
(g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 10 - 13 945 - 1,890 945 - 1,890
4 to < 7 yr 14 - 20 1,365 - 2,415 1,365 - 2,445
7 to < 11 yr 20 - 28 1,730 - 3,465 1,730 - 3,465
Women
11 to < 15 yr 30 - 40 1,575 - 3,150 1,575 - 3,150
15 to < 19 yr 40 - 45 1,260 - 3,150 1,260 - 3,150
> 19 yr 45 - 47 1,785 - 2,625 1,875 - 2,525
Men
11 to < 15 yr 30 - 42 2,100 - 3,885 2,100 - 3,885
15 to < 19 yr 42 - 49 2,200 - 4,095 2,200 - 4,095
> 19 yr 49 - 55 2,625 - 3,465 2,625 - 3,465
1
2
3
Protein intake may need to be increased if sodium benzoate is prescribed.
4
Modified from reference 4. Under normal circumstances, offer minimum of 1.5 mL fluid and 1.0 mL fluid to children
and adults to neonates for each kcal ingested.
Table 12-2. Servings Lists for Protein-Restricted Diets: Approximate Protein and Energy Content per
Serving
Food List Nutrient

Protein Energy
(g) (kcal)
Breads/cereals 0.6 30
Fats 0.1 60
Fruits 0.5 60
Vegetables 0.5 10
Free Foods A 0.1 65
Free Foods B 0.0 55
Pro-Phree ® Protein-Free Energy Module With Iron, Vitamins & Minerals, 100 g 0.00 510
Similac With Iron Infant Formula, Ready to Feed, 100 mL 1.40 68
1
1
From reference 23.

TABLE 12-3. Nonketotic Hyperglycinemia Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

Length/ Weight Head Plasma GLY Free Carnitine Hgb Hct Ferritin Transthyretin Protein Energy
Height Circum
(mo/d/yr) (yrs/mos) (cm) (kg) (cm) (µmol/L) (µmol/L) (g/dL) (%) (ng/mL) (mg/dL) (g) (kcal)
Nonketotic Hyperglycinemia 227
REFERENCES
1. Alemzadeh R, Gammeltoft K, Matteson K: Efficacy of low-dose dextromethorphan in the treatment of nonketotic

hyperglycinemia. Pediatrics 1996;97:924-926.
2. Apostolidou I, Papagaroufalis C, Michelakakis H, et al: Non-ketotic hyperglycinaemia: A therapeutic approach.
Dis 2000;23 Suppl 1:29A.
1996.
5. Boneh A, Degani Y, Harari M: Prognostic clues and outcome of early treatment of nonketotic hyperglycinemia.
Pediatr Neurol 1996;15:137-141.
1985.
7. Flannery DB, Pellock J, Bousounis D, et al: Nonketotic hyperglycinemia in two retarded adults: A mild form of
infantile nonketotic hyperglycinemia. Neurology 1983;33:1064-1066.
9. Hamosh A, Johnston MV: Nonketotic hyperglycinemia. In Scriver CR, et al (eds): The Metabolic and Molecular
Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing Division, 2001, pp 2065-2078.
10. Hamosh A, Maher JF, Bellus GA, et al: Long-term use of high-dose benzoate and dextromethorphan for the
treatment of nonketotic hyperglycinemia. J Pediatr 1998;132:709-713.
11. Hamosh A, McDonald JW, Valle D, et al: Dextromethorphan and high-dose benzoate therapy for nonketotic
hyperglycinemia in an infant. J Pediatr 1992;121:131-135.
12. Holmgren G, Blomquist HK: Nonketotic hyperglycinemia in two sibs with mild psychoneurological symptoms.
Neuropediatrie 1997;8:67-69.
13. Holmquist P, Polberger S: Neonatal nonketotic hyperglycinemia (NKH): Diagnosis and management in two cases.
Neuropediatrics 1985;16:191-193.
14. Inoue F, Matsuo S, Yoshioka H, et al: Tryptophan therapy for non-ketotic hyperglycinaemia. J Inher Metab Dis
1992;15:399-401.
15. Kure S, Narisawa K, Tada K: Enzymatic diagnosis of nonketotic hyperglycinemia with lymphoblasts. J Pediatr
1992;120:95-98.
16. Leuzzi V, Morano S, Moretti F, et al: Nonketotic hyperglycinemia: A new case with late onset. J Inher Metab Dis
1990;13:238.
1982.
1987;1:1-17.
19. Matalon R, Naidu S, Hughes JR, Michals K: Nonketotic hyperglycinemia: Treatment with diazepam - A competitor
for glycine receptors. Pediatrics 1983;71:581-584.
20. Matsuo S, Inoue F, Takeuchi Y, et al: Efficacy of tryptophan for the treatment of nonketotic hyperglycinemia: A
new therapeutic approach for modulating the N-methyl-D-aspartate receptor. Pediatrics 1995;95:142-146.
21. Neuberger JM, Schweitzer S, Rolland MO, Burghard R: Effect of sodium benzoate in the treatment of atypical
nonketotic hyperglycinaemia. J Inher Metab Dis 2000;23:22-26.
22. Ohya Y, Ochi N, Mizutani N, et al: Nonketotic hyperglycinemia: Treatment with NMDA antagonist and
consideration of neuropathogenesis. Pediatr Neurol 1991;7:65-68.
23. Posati LP, Orr ML: Composition of Foods: Dairy and Egg Products, Agricultural Handbook No. 8 - 1.
Washington, DC: US Dept of Agriculture, Agricultural Research Service, 1976.
24. Press GA, Barshop BA, Haas RH, et al: Abnormalities of the brain in nonketotic hyperglycinemia: MR
manifestations. AJNR 1989;10:315-321.
25. Pueschel SM, Cha C-JM, Langon T: Therapeutic attempts in infants with nonketotic hyperglycinaemia. J Ment
Defic Res 1981;25:61-69.
26. Schiffman R, Borch A, Ergaz Z, Glick B: Nonketotic hyperglycinemia presenting with pin-point pupils and
hyperammonemia. Isr J Med Sci 1992;28:91-93.
27. Schmitt B, Steinmann B: Dextromethorphan in infantile nonketotic hyperglycinemia. J Pediatr 1993;122-324-325.
28. Schmitt B, Steinmann B, Gitzelmann R, et al: Nonketotic hyperglycinemia: Clinical and electrophysiologic effects
of dextromethorphan, an antagonist of the NMDA receptor. Neurol 1993;43:421-424.
29. Schmitt B, Steinmann B: Dextromethorphan in a child with nonketotic hyperglycinaemia - A 6-year follow up. Eur J
Pediatr 1998;157:349-350.
1976.

1983;7:280-288.
1989;143:828-832.
33. Tada K: Tada K: Nonketotic hyperglycinemia. In Fernandes J, et al (eds): Inborn Metabolic Disease, ed 3. New
York: Springer, 2000, pp 255-258.
34. Tada K, Kure S, Takayanagi M: Non-ketotic hyperglycinemia: A life-threatening disorder in the neonate. Early Hum
Dev 1992;29:75-81.
35. Tegtmeyer-Metzdorf H, Roth B, Günther M, et al: Ketamine and strychnine treatment of an infant with nonketotic
hyperglycinaemia. Eur J Pediatr 1995;54:649-653.
36. Toone JR, Applegarth DA, Levy HL: Prenatal diagnosis of non-ketotic hyperglycinaemia: Experience in 50 at-risk
pregnancies. J Inher Metab Dis 1994;17:342-344.
37. Trijbels JF, Monnens LAH, van der Zee SPM, et al: A patient with nonketotic hyperglycinemia: Biochemical
findings and therapeutic approaches. Pediatr Res 1974;8:598-605.
38. Van Hove JL, Kishnani P, Muenzer J, et al: Benzoate therapy and carnitine deficiency in non-ketotic
hyperglycinemia. Am J Med Genet 1995;59:444-453.
1977;30:1269-1280.
40. Wiltshire EJ, Poplawski NK, Harrison JR, Fletcher JM: Treatment of late-onset nonketotic hyperglycinaemia:
Effectiveness of imipramine and benzoate. J Inher Metab Dis 2000;23:15-21.
41. Wolff JA, Kulovich S, Yu AL, et al: The effectiveness of benzoate in the management of seizures in nonketotic
hyperglycinemia. Am J Dis Child 1986;140:596-602.

PROTOCOL 13 — Propionic or Methylmalonic Acidemia

PROPIMEX ®-1 and PROPIMEX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
Propionic acidemia (PA) and methylmalonic acidemia (MMA) are disorders of essential isoleucine
(ILE), methionine (MET), threonine (THR), and valine (VAL) and odd-chain-fatty acid metabolism
resulting from a defect in the genes that encode for propionyl-CoA carboxylase (PCC) and
methylmalonyl-CoA mutase (MMM), respectively (Figure L). PCC requires biotin as a coenzyme while
MMM requires adenosylcobalamin as coenzyme (13). Biotin-responsive PA has been described, but
patients still require medical and nutrition intervention.
Both PA and MMA are heterogeneous in their clinical presentation and outcome. In patients with PA,
activity of PCC is not totally absent, but ranges from 1% to 5% of normal as shown in cultured skin
fibroblasts (13). Mutations in MMM vary from no functional mutase (Muto) to structurally altered
mutase with decreased affinity for adenosylcobalamin and reduced stability (Mut—). Children with
these mutations do not respond to cobalamin therapy and require a special diet. Several abnormalities
in the reduction of cobalamin result in impaired MMM activity and some of these children respond to
pharmacologic doses of hydroxycobalamin with enhancement of enzyme activity and increased
tolerance of ILE, MET, THR, and VAL.
Isoleucine
Methionine
Threonine
Valine
Odd-chain fatty acids (OCFA)
Excess polyunsaturated fatty acids (PUFA)
Biotin Adenosylcobalamin
Propionyl-CoA* L-Methylmalonyl-CoA** Succinyl-CoA
Propionyl-CoA Methylmalonyl-CoA mutase

carboxylase
* Accumulates in untreated MMA

and PPA
Propionic acid* + L-Carnitine Methylmalonic acid** ** Accumulates in untreated
MMA
Indicates site of
enzyme defect
Propionyl-carnitine
Figure L. Propionate and methylmalonate metabolism in propionic and methylmalonic acidemias

Symptoms in patients with severe PA or MMA usually present within the 1st days of life and include
acute or chronic vomiting (18), poor feeding, failure to thrive, dehydration, hypotonia, and severe
metabolic acidosis (31). To a lesser extent, hypoglycemia and hyperammonemia may be present (45,
70). Hyperglycinemia occurs in both of these disorders. Some patients with PA or MMA present in late
infancy or childhood with infection or after ingesting large amounts of protein. Symptoms in later
presenting patients are usually milder than in early-presenting patients and they may tolerate more
intact protein than patients who present as neonates.
© 2001 Ross Products Division Propionic Acidemia/Methylmalonic Acidemia 235
Laboratory findings for PA and MMA include accumulation of organic acids characteristic of each
disorder in body fluids (eg, propionylcarnitine, methylcitrate, 3-OH-propionate, propionylglycine, tiglic
acid, propionate, and methylmalonate). Vitamin B12 deficiency must be excluded when excessive
urinary MMA is found (8). PA has an incidence of about 1/100,000 live births (31). More than
100 patients have been described with MMA (mutase deficiency) (13). Both disorders are autosomal
recessive.

For patients with MMA, morbidity and mortality are based, in part, on the biochemical lesion. Patients
with Muto have the poorest outcome and survival rate. Both mutº and mut— patients may have
developmental delay, dystonia, and chronic renal failure (40), which may require renal transplantation
(66). Patients with PA may suffer from pancreatitis (6, 23, 25) and recurrent infection (2). Poorly
controlled patients with either MMA or PA may be immunocompromised (13, 20, 37, 55). Despite
improved outcomes, patients suffer from growth retardation, chronic anorexia, neurologic impairment
(17), pathophysiologic changes in the brain (16), and cardiomyopathy (4, 28). Early intervention and
appropriate nutrition support can result in normal growth and outcome in these patients (4, 30, 44, 64).
The use of parenteral nutrition support during acute crises has minimized catabolism and improved
recovery in these patients (22, 24).
Improvement in survival of patients reflects early diagnosis, rapid intervention during acute medical
crisis, and improved treatment (4). Successful use of therapy has resulted in women surviving to the
child-bearing years, offering new challenges to metabolic clinicians (63). Liver transplantation and
combined liver-kidney transplantation (MMA) have been used with mixed results (41, 65, 66).

A. The Defect
1. PA results from deficient activity of PCC.
a. Biotin-responsive PA has been described; patients still require nutrition support (58, 69).
2. Six types of MMA have been defined, based on enzyme complementation studies (13).
a. Some patients may respond to pharmacologic doses of intramuscular hydroxycobalamin,
and may not require other nutrition support.
3. Nutrition therapy for vitamin-nonresponsive forms of PA and MMA is the same.
1. Infants or children who have any of following clinical and/or laboratory signs should be
evaluated for PA and MMA (13, 31).
a. Ketoacidosis, low blood pH, hyperlacticacidemia.
b. Hypertonia, areflexia.
c. Hyperventilation, apnea.
d. Vomiting, dehydration, failure to thrive.
e. Hyperammonemia, hyperglycinemia.
f. Neutropenia, thrombocytopenia, pancytopenia, anemia.
g. Lethargy and coma followed by death, if untreated.
h. Blood glucose may be normal, reduced, or elevated.

1. Restrict dietary ILE, MET, THR, VAL, and odd-chain-fatty acids to maintain biochemical
homeostasis.
2. Restrict dietary polyunsaturated fatty acids.
1. Administer pharmacologic doses of oral biotin if PCC activity is present in patients with PA.
2. Administer pharmacologic doses of intramuscular hydroxycobalamin if MMM activity is
present in patients with MMA.
V. Nutrition Support During Acute Illness and at Diagnosis

236 Propionic Acidemia/Methylmalonic Acidemia © 2001 Ross Products Division

B. Comatose or Neurologically Depressed Patients
1. For medical management during diagnosis and acute care, see references 13 and 31.
2. Begin MET- and VAL-free nasogastric feeding of protein, energy, and L-carnitine (Propimex)
36 to 48 hours after beginning dialysis with amino acid-free dialysate. Intravenous sodium
phenylacetate and sodium benzoate reduce blood ammonia concentrations in PA (35).
a. See Table 13-1, p 241, for Recommended Protein, Energy, and Fluid Intakes.
b. See Table 13-2, p 242, for composition of Propimex.
c. See Appendix 26, p A-28, for sources of L-carnitine (in addition to that in Propimex) and
sodium phenylacetate
3. Begin intravenous infusion of Liposyn ® II (Appendix 26, p A-28) and 10% D-glucose during
nasogastric feeding and continue until patient is medically stable.
4. Three approaches may be used to supply ILE, MET, THR, and VAL.
a. Approach One.
1) After 24-48 hours of Propimex as the only protein source:
i. Displace one-half the protein supplied by Propimex with intact protein (Table 13-3,
p 243).
b. Approach Two.
1) After 24-48 hours of Propimex as the only protein source:
i. Supply the VAL (Table 13-1, p 241) prescription with infant formula with iron
(Table 13-3, p 243).
a) Use lowest recommended VAL intake (Table 13-1, p 241).
b) Use disposable syringe to measure liquid infant formulas and gram scale to
measure powdered infant formula.
c) Decrease amount of protein supplied by Propimex by the amount of intact
protein in infant formula required to supply VAL.
ii. If ILE and THR prescriptions (lowest) (Table 13-1, p 241) are not met by Propimex
and infant formula, supply with pure solutions (Appendix 26, p A-28) (10 mg/mL -
1.0 g of L-amino acid with boiled, cooled water added to make 100 mL).
a) Use disposable syringe to measure pure L-amino acid solutions.
iii. MET intake will be within the prescribed range (Table 13-1, p 241)
c. Approach Three.
1) Parenteral amino acid solutions, if indicated (Appendix 26, p A-28) (22, 24).
Warning: Plasma amino acid concentrations must be assessed daily until ILE, MET,
THR, and VAL prescriptions maintain plasma amino acid concentrations at
the lower limit of reference ranges given in Section VI.A.I, below.
5. Energy.
a. Use Polycose ® Glucose Polymers (3.8 kcal/g, 2 kcal/mL) and peanut oil (7.96 kcal/mL) to
supply prescribed energy not provided by Propimex and infant formula with iron.
1) Use peanut oil as an energy source only if the osmolarity of the medical food mixture
is > 450 mosm/L.
i. See Appendices 18 and 19, pp A-20 and A-21 for mathematical formula and
osmolarity of foods.

1. Maintain 2- to 4-hour postprandial plasma amino acid concentrations in ranges noted below,
measured by quantitative methods, or near the lower limit of normal ranges established in
laboratory used.
GLY 115 - 290 0.9 - 2.2
ILE 25 - 105 0.3 - 1.4
MET 18 - 45 0.3 - 0.7
THR 45 - 250 0.5 - 3.0
VAL 65 - 250 0.8 - 2.9

in adults.
a. Prevent catabolism and ketosis (13, 31, 42, 68).
b. Avoid prolonged fasting (60).
4. Maintain adequate hydration (31, 71).
5. Maintain blood ammonia in normal range: < 35 µmol/L (enzymatic method) (61), < 33 µmol/L
(resin method), or in normal range established by laboratory used.
C. Urine Metabolites
1. Maintain urine free of, or containing only trace abnormal metabolites (propionic acid,
methylcitrate, 3-hydroxypropionate) and methylmalonic acid (found only in MMA) (31).
Note: Urinary propionylcarnitine concentrations may be chronically elevated even
with nutrition therapy.

A. Protein
1. Prescribe, initially, amount greater than Recommended Dietary Allowances (RDAs)
(Table 13-1, p 241) (14).
c. Rapid catabolism of amino acids (7, 21, 48).
Warning: Inadequate protein intake will result in failure to thrive in infants; poor growth
in children; weight loss in adults; low plasma transthyretin concentration,
osteopenia, hair loss in children and adults; and decreased tolerance of ILE,
MET, THR, and VAL.
B. ILE, MET, THR, VAL
1. Prescribe intakes that promote goals of nutrition support (Table 13-1, p 241).
2. ILE, MET, THR, and VAL requirements vary widely:
a. From patient to patient, depending on activity of catabolic enzymes and genotype.
b. In same patient depending on:
1) Age.
2) Growth rate.
4) State of health.
a. Plasma GLY, ILE, MET, THR, VAL, and propionic or methylmalonic acid concentrations.
b. Urine concentrations of propionic or methylmalonic acid and their catabolites.
d. With ILE, MET, THR, and VAL in low-normal range, plasma amino acid concentrations
must be measured frequently to prevent deficiency.
Warning: Inadequate intakes of ILE, MET, THR, and VAL result in adverse effects:
ILE deficiency (50): Weight loss or no weight gain; redness of buccal mucosa;
fissures at corners of mouth; tremors of extremities; decreased plasma
cholesterol and ILE; increased concentrations of plasma lysine,
phenylalanine (PHE), serine (SER), tyrosine (TYR), and VAL; skin
desquamation (11), and corneal de-epithelialization (62).

MET deficiency (51): Decreased plasma MET and cholesterol and increased
plasma PHE, proline, SER, THR, and TYR concentrations.
THR deficiency (36): Arrested weight gain; glossitis and redness of buccal
mucosa; and decreased plasma THR and globulin concentrations.
VAL deficiency (52): Poor appetite, drowsiness; excessive irritability and
crying in infants; weight loss or decrease in weight gain; and decreased
plasma albumin concentration.
C. Energy
Warning: Inadequate energy intake may result in failure to thrive in infants, poor growth
in children, weight loss in adults, and low tolerance of restricted amino acids.
Catabolism increases ketone production and plasma concentrations of odd-
chain-fatty acids.
D. L-Carnitine (56, 57)
1. Prescribe amount required to maintain normal plasma free carnitine concentration > 30 µmol/L.
a. Suggested intake is between 100 and 300 mg/kg body weight.
2. Ingestion of excess oral L-carnitine may cause gastrointestinal distress and fish odor
(trimethylamines).
E. Fluid
1. Prescribe amount that will supply water requirements (Table 13-1, p 241).
2. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid to
3. Requirements may be higher than recommended secondary to accompanying fever and
catabolic crises.
F. D-Biotin
1. Patients with residual PCC activity may respond to pharmacologic doses of D-biotin, with
increased tolerance of ILE, MET, THR, and VAL.
2. Prescribe 5 to 10 mg D-biotin daily for patients with PA (Appendix 26, p A-28).
G. Odd-chain-Fatty Acids
1. Avoid dietary sources of odd-chain-fatty acids, including butter, cream, lard, olive oil, excess
polyunsaturated fatty acids, and breads containing added sodium or calcium propionate.
2. Inhibit catabolism and loss of adipose tissue by maintaining adequate nutrition status and
preventing weight loss.

A. Protein
1. Initiate protein prescription with highest recommended intake for age (Table 13-1, p 241).
2. Calculate amount of infant formula with iron, beikost, skim milk, or table foods (Tables 13-3,
p 243) required to fill approximately 50% of protein prescription.
a. See Serving Lists for ILE-, MET-, THR- and VAL-Restricted Diets (Table 13-3, p 243) for
average nutrient content per serving.
4. Supply any remaining prescribed protein with Propimex (Table 13-2, p 242).
a. Propimex-1 is for infants and toddlers and Propimex-2 is for children, adolescents, and
adults.
b. Weigh Propimex powder on scale that reads in grams because of variability of household
c. See Table 13-2 (p 242, footnote 3) for approximate packed weight of Propimex powder in

B. ILE, MET, THR, and VAL
1. Calculate amounts of ILE and THR provided by Propimex (contains small amounts of ILE and
THR) (Table 13-2, p 242) and infant formula, beikost, skim milk, or table foods (Table 13-3,
p 243).
2. Compare sum of these amino acids to ranges found in Recommended Daily Nutrient Intakes
(Table 13-1, p 241). Sum of these amino acids will vary based on type and amount of intact
protein prescribed.
3. Either ILE or VAL in foods may be used as a marker to determine if more intact protein is
required.
a. If protein prescription provides total dietary ILE or VAL below minimum for age, increase
intact protein to obtain at least minimum for age (Table 13-1, p 241).
C. Energy
1. Calculate energy provided by Propimex (Table 13-2, p 242) and infant formula, beikost, skim
milk, or table foods (Table 13-3, p 243) required to fill protein prescription.
Energy Module with Iron, Vitamins & Minerals Powder (Appendix 11, p A-10); sugar (48
kcal/Tbsp); or Free Foods B (Table 13-3, p 243).
1. If L-carnitine in Propimex is inadequate to maintain normal concentration of plasma free
carnitine, add liquid L-carnitine to medical food mixture.
2. Measure L-carnitine solution with disposable syringe if entire contents of container are not
used.
a. If L-carnitine is not added to medical food mixture, administer TID or QID with meals.
3. L-carnitine may be added to puréed foods and fruit juices.
1. Add sufficient boiled, cooled water to infant formula, Propimex, carbohydrate (if needed), and
L-carnitine (if needed) to yield prescribed volume. Tap water may replace boiled, cooled water
when preparing Propimex for older infants, children, and adults.
4. Do not use terminal sterilization because of Maillard reaction (Practical Aspects of Nutrition
Support, p viii).
before feeding.
8. For children and adults, chill Propimex medical food mixture to improve taste.
F. Diet Guide
each diet change.

a. See Table 13-2, p 242, for composition of Propimex and Table 13-3, p 243, for
composition of infant formulas and skim milk.
formulas.
not available.
c. If Propimex-1 provides < 100% of RDIs for infants and < 75% for children and adults,
supplement diet with minerals and vitamins if not provided by beikost or table foods and
B. Osmolarity
b. Approximate osmolarity per gram of Propimex is listed in Appendix 19, p A-21.
adults or is greater than tolerated by patient, increase water content of prescribed medical
food mixture and recalculate its osmolarity (26, 49).
renal solute load.
Warning: Patients with MMA diagnosed with end-stage renal disease will have reduced
renal concentrating ability.
recalculate.

A. Plasma GLY, ILE, MET, THR, and VAL Concentrations
1. Initial.
a. Measure daily by quantitative methods until plasma concentrations stabilize and
approximate requirements for ILE, MET, THR, and VAL are known.
b. Plasma GLY is often elevated in patients with PA or MMA (13, 31). Improvement in
plasma GLY concentration suggests better metabolic control.
2. Ongoing.
b. Evaluate 1 to 2 times weekly until patient is 6 months old and at least monthly thereafter.
3. Unacceptable ILE, MET, THR, and VAL concentrations.
a. If either plasma ILE, MET, THR, or VAL concentration is not detected and patient has
ingested the full prescription:
1) Increase prescribed amount of undetected amino acid(s) by 10% to 25% using intact
protein and reevaluate plasma concentrations in 3 days.
2) If plasma ILE, MET, THR, or VAL concentration continues undetected, repeat above
b. If plasma ILE concentration is < 25 µmol/L, plasma MET concentration is < 18 µmol/L,
plasma THR concentration is < 45 µmol/L, or plasma VAL concentration is < 65 µmol/L,
and patient has ingested full prescription:
1) Increase intact protein intake by 5% to 10% if concentrations of more than two amino
acids are low.
2) Repeat above process until value is in treatment range if plasma ILE, MET, THR, or
VAL concentration continues to be low.
3) Individual supplementation of ILE and VAL may be required if tolerance to intact
protein is limited. Supplements may be prepared using a sterile solution containing 10
mg amino acid/mL (ie, 1.0 g amino acid to make 100 mL total volume) (Appendix 26,
p A-28).
c. If plasma ILE concentration is > 105 µmol/L, plasma MET concentration is > 45 µmol/L,
plasma THR concentration is > 250 µmol/L, or plasma VAL concentration is > 250 µmol/L
and patient is not ill and has not ingested more or less protein and energy than prescribed:
1) Decrease prescribed amount of intact protein or L-amino acids by 5% to 10% and
reevaluate plasma concentration in 1 week.
2) If plasma ILE, MET, THR, or VAL concentration continues to be high, repeat above
B. Blood Ammonia Concentration
1. Initially, measure as clinically indicated until concentration is stabilized in normal range.
a. Blood ammonia concentrations may indirectly reflect plasma methylmalonic and propionic
acid concentrations (9, 46).
2. If blood ammonia concentration is > 35 µmol/L or greater than normal as established in
laboratory used:
a. Decrease ILE, MET, THR, and/or VAL from intact protein by 5% to 10% and reevaluate
blood concentration in 3 days. Be certain to maintain adequate energy and protein intakes
from Propimex.
b. Gradually increase restricted amino acids as tolerated to original prescription.
C. Plasma or Urine Organic Acids
1. Measure monthly if plasma amino acid concentrations are greater than normal.
a. Organic acids measured differ depending on disorder.
2. Measure urine ketoacids daily by Ketostix ® (71).
a. Urine should be free of ketoacids at all times (negative Ketostix result).
3. If urine contains ketoacids (positive Ketostix result):
a. Suggests catabolism and impending illness. Catabolism from insufficient protein and
energy intakes requires nasogastric or gastrostomy tube feeding (25, 30, 64).
b. Immediately obtain blood sample for evaluation of amino acid concentrations.
c. Brief metabolic physician immediately on patient's illness.
4. Metronidazole, an antibiotic, can reduce urinary excretion of propionate from colonic gut flora
(29). Dosages vary from 10 to 20 mg/kg/day over a 1- to 2-week period (59).
Warning: Children with MMA and diagnosed renal failure may excrete reduced amounts
of MMA (10).
D. Protein Status
1. Evaluate plasma transthyretin concentration every 3 months until 1 year of age and twice
concentration in 1 month. If ILE, MET, THR, and VAL concentrations are in treatment
range, use Propimex to increase protein.
normal range.
E. Iron Status
standards).
b. Evaluate more frequently if anemia persists.
1) Persistent anemia suggests chronic elevation in toxic metabolites that inhibit stem cell
differentiation (20).
F. Plasma Carnitine Concentration
1. Plasma free carnitine concentration should be evaluated as necessary to maintain normal
concentration (≥ 30 µmol/L).
G. Growth Status
a. Measure monthly to 1 year, every 3 months to 4 years of age, and every 6 months
thereafter. Plot measurements of infants and children on NCHS growth charts.
a. Increase protein and energy prescriptions by 5% to 10% and remeasure after 1 month.
achieved.
c. If patient remains below usual growth channel and does not respond to increase in protein
and energy or cannot consume diet prescribed through oral feedings, nasogastric or
gastrostomy tube feeding should be seriously considered (25, 30, 64).
H. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of ILE, MET, THR, VAL, protein, and energy before each blood test.
not available.
b. See Appendix 28, p A- 29, for information about ordering software for diet evaluation.
Warning: Anorectic patients require gastrostomy tube feedings which may limit intake
if diets are not carefully planned. Gastrostomy tube feedings may improve
morbidity (25, 30, 64) when the patient cannot meet energy and nutrient
requirements by oral feeds.
I. Clinical Summary

A. Example 1
Establish and fill prescription for 1-month-old infant weighing 4.14 kg using Recommended Daily
Nutrient Intakes from Table 13-1, p 241, and average nutrient contents from Tables 13-2 and
13-3, pp 242 and 243.

ILE 108 mg/kg x 4.14 kg = 447 mg
MET 45 mg/kg x 4.14 kg = 186 mg
THR 108 mg/kg x 4.14 kg = 447 mg
VAL 104 mg/kg x 4.14 kg = 431 mg
L-carnitine 100 mg/kg x 4.14 kg = 414 mg
Medical Food Mixture Measure ILE MET THR VAL L-Carn Protein Energy
(mg) (mg) (mg) (mg) (mg) (g) (kcal)
Propimex-1 48 g 58 0 48 0 432 7.2 230
Similac ® With Iron, Ready to 518 mL 388 181 399 430 0 7.2 352
Feed
Total per day 446 181 447 430 432 14.4 582
Total per kg 108 44 108 104 104 3.5 141
load ≤ 150 mosm.
B. Example 2
Nutrient Intakes from Table 13-1, p 241, and average nutrient contents from Tables 13-2 and 13-
3, pp 242 and 243.
ILE 690 mg/day
MET 255 mg
THR 650 mg
VAL 720 mg
L-carnitine (100 mg/kg) 1,900 mg
Protein 35.0 g
Energy 2,000 kcal
Fluid 2,000 mL

Medical Food Mixture Measure ILE MET THR VAL L-Carn Protein Energy
(mg) (mg) (mg) (mg) (mg) (g) (kcal)
Propimex-2 64 g 154 0 128 0 1,152 19.2 262
Skim milk 32 mL 68 28 51 76 0 1.1 12
Sugar 96 g (1/2 cup) 0 0 0 0 0 0.0 384
L-carnitine 1 7.5 mL 0 0 0 0 750 0.0 0
Food List Servings

2
Breads /Cereals 12 300 120 300 420 0 8.4 360
Fats 6 30 12 30 30 0 0.6 180
Fruits 6 60 30 60 90 0 3.0 330
Vegetables 5 75 25 75 100 0 2.5 50
Free Foods A 2 8 4 8 10 0 0.2 130
Free Foods B 6 0 0 0 0 0 0.0 330
Total per day 695 219 652 726 1,902 35.0 2,038
1
Add only if plasma free carnitine concentration is < 30 µmol.
2
Many commercial breads contain propionic acid as an antimicrobial and flavoring agent. These breads
should not be used.

A. Rationale
protein (67).
2. Well-nourished infants, children, and adults with PA or MMA respond to infection and trauma
as do normal persons.
3. Extent of protein catabolism determines subsequent elevation in concentrations of plasma
and urine organic acids, odd-chain-fatty acids, and ketones.
a. See Nutrition Support During Acute Illness and at Diagnosis, Section V, p 231.

TABLE 13-1. Recommended Daily Nutrient Intakes (Range) for Infants, Children, and Adults With Propionic
or Methylmalonic Acidemia
Age Nutrient
1,2 1,2 1,2 1,2 3 3 4
ILE` MET THR VAL Protein Energy Fluid
(mg/kg) (mg/kg) (mg/kg) (mg/kg) (g/kg) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 75 - 120 30 - 50 75 - 135 75 - 105 3.50 - 2.50 (130) 95 - 145 125 - 200
3 to < 6 mo 65 - 100 20 - 45 60 - 100 65 - 90 3.50 - 2.50 (125) 95 - 145 130 - 160
6 to < 9 mo 50 - 90 10 - 40 40 - 75 35 - 75 3.00 - 2.50 (120) 80 - 135 125 - 145
9 to < 12 mo 40 - 80 10 - 30 20 - 40 30 - 60 3.00 - 2.50 (115) 80 - 135 120 - 135
(mg/day) (mg/day) (mg/day) (mg/day) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 485 - 735 180 - 390 415 - 600 550 - 830 ≥ 30.0 1,300 ( 900 - 1800) 900 - 1,800
4 to <7 yr 630 - 960 255 - 510 540 - 780 720 - 1,080 ≥ 35.0 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 715 - 1,090 290 - 580 610 - 885 815 - 1,225 ≥ 40.0 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 965 - 1,470 390 - 780 830 - 1,195 1,105 - 1,655 ≥ 55.0 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 965 - 1,470 275 - 780 830 - 1,195 1,105 - 1,655 ≥ 55.0 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr 925 - 1,410 265 - 750 790 - 1,145 790 - 1,585 ≥ 50.0 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 540 - 765 290 - 765 810 - 1,170 1,080 - 1,515 ≥ 50.0 2,700 (2000 - 3700) 2,000 - 3,700
15 to <19 yr 670 - 950 475 - 950 1,010 - 1,455 1,345 - 2,015 ≥ 65.0 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr 1,175 - 1,190 475 - 950 1,010 - 1,455 1,345 - 2,015 ≥ 65.0 2,900 (2000 - 3300) 2,000 - 3,300
1
Modified from references 1, 12, 38, and 72.
2
Initiate prescription with lowest recommended intake for age. Modify prescription based on frequently obtained plasma values and growth in
infants and children and frequently obtained plasma values and weight maintenance in adults.
3
Modified from references 14 and 53. When possible, initiate prescription with highest value. Modify prescription based on plasma
transthyretin concentration and weight.
4
From reference 5. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to children and adults for each kcal
ingested.

TABLE 13-2. Nutrient Composition of PROPIMEX ®-1 1, 3, and PROPIMEX ®-2 2, 3
Nutrient Propimex-1 Propimex-2

Energy, kcal 480 32 410 13.7
Nitrogen, g 2.40 0.160 4.80 0.160
Protein equiv, g 15.00 1.000 30.00 1.000
5
Amino acids , g 16.17 1.078 32.34 1.078
Cystine, g 0.45 0.030 0.90 0.030
Histidine, g 0.42 0.028 0.84 0.028
Isoleucine, g 0.12 0.008 0.24 0.008
Leucine, g 1.38 0.092 2.76 0.092
Lysine, g 1.00 0.067 2.00 0.067
Methionine, g trace 0 trace 0
Phenylalanine, g 0.88 0.059 1.76 0.059
Threonine, g 0.10 0.007 0.20 0.007
Tryptophan, g 0.17 0.011 0.34 0.011
Tyrosine, g 0.89 0.059 1.78 0.059
Valine, g trace 0 trace 0
Carnitine, mg 900 60 1,800 60
Taurine, mg 40 2.66 50 1.67
Carbohydrate, g 53.0 3.53 35.0 1.17
Fat, g 21.7 1.45 13.0 0.43
4 5
Linoleic acid, g 2.00 0.133 2.00 0.07
6 7
0.36 0.024 0.17 0.006
Minerals
Calcium, mg 575 38 880 29
Chloride, mg/mEq 410/11.56 27/0.77 1,160/32.72 38.7/1.09
Chromium, µg 11 0.73 27 0.90
Copper, mg 1.10 0.073 1.00 0.033
Iodine, µg 65 4.33 100 3.33
Iron, mg 9.0 0.6 13.0 0.43
Magnesium, mg 50 3.33 225 7.5
Manganese, mg 0.50 0.033 0.80 0.027
Potassium, mg/mEq 675/17.26 45/1.15 1370/35.04 45.7/1.17
Selenium, µg 20 1.33 35 1.17
Sodium, mg/mEq 190/8.26 12.7/0.55 880/38.28 29.3/1.28
Zinc, mg 8.0 0.53 13 0.43
Vitamins
A, µg RE 420 28 660 22
D, µg 7.50 0.50 7.50 0.25
E, mg α-TE 10.10 0.67 12.10 0.40
K, µg 50 3.33 60 2.00
Biotin, µg 65 4.3 100 3.33
B6, mg 0.75 0.05 1.30 0.043
B12, µg 4.90 0.33 5.00 0.167
Choline, mg 80 5.3 100 3.33
Folate, µg 230 15 430 14.33
Inositol, mg 40 2.7 70 2.33
Niacin equiv, mg 12.8 0.85 21.7 0.72
Riboflavin, mg 0.90 0.06 1.80 0.060
Thiamin, mg 1.90 0.127 3.25 0.108
1 2
3
Approximate packed weight of Propimex-1 and Propimex-2 in level, dry US standard household measures:
Propimex-1 Propimex-2
1 Tbsp = 7g 8g
1/4 cup = 26 g 32 g
1/3 cup = 35 g 41 g
1/2 cup = 53 g 61 g
1 cup = 105 g 117 g
4 5
6 7

TABLE 13-3. Serving Lists for ILE-, MET-, THR-, and VAL-Restricted Diets: Average Nutrient Content per
Serving
Food List Nutrient

ILE MET THR VAL Protein Energy
(mg) (mg) (mg) (mg) (g) (kcal)
Breads1/Cereals 25 10 25 35 0.70 30
Fats 5 2 5 5 0.10 30
Fruits 10 5 10 15 0.50 55
Vegetables 15 5 15 20 0.50 10
Free Foods A 4 2 4 5 0.10 65
Free Foods B 0 0 0 0 0.00 55
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 109 54 88 141 1.86 68
2
Isomil ® Soy Formula With Iron, Ready to Feed, 100 mL 2 81 40 70 70 1.66 68

2
Similac ® With Iron Infant Formula, Ready to Feed, 100 mL 75 35 77 83 1.40 68
Skim milk, 100 mL 3 213 89 159 236 3.53 36
1
Many commercial breads contain propionic acid as antimicrobial and flavoring agent. These breads should not be
used. Read labels carefully.
2
3

TABLE 13-4. Serving Lists for ILE-, MET-, THR- and VAL-Restricted Diets: Gerber ® Baby Foods (Beikost)
1
Food Weight Approximate ILE MET THR VAL Protein Energy

(g) Measure (mg) (mg) (mg) (mg) (g) (kcal)
BREADS AND CEREALS
Baked Finger Snacks, Graduates

Animal crackers, cinnamon graham 14 3-1/2 crackers 29 11 17 36 0.8 36
Apple cinnamon cookie 10 1 cookie 26 12 20 31 0.8 43
Arrowroot cookie 10 2 cookies 26 13 20 31 0.8 46
Banana cookie 12 1-1/2 cookies 28 16 18 34 0.8 52
Pretzel 6 2 pretzels 28 12 17 32 0.8 23
Strawberry fruit bar 13 1-1/2 bars 28 17 21 34 0.7 53
Veggie crackers 12 17 crackers 29 12 22 34 0.6 57
Cereals, Dry
Barley 6 1 Tbsp + 2 tsp 27 13 23 37 0.8 23
Mixed 8 2 Tbsp 26 17 19 34 0.8 31
Oatmeal 4 1 Tbsp + 1 tsp 23 11 18 31 0.6 16
Oatmeal/banana 5 1 Tbsp + 2 tsp 26 10 23 34 0.7 24
Oatmeal/mixed fruit 6 1 Tbsp + 2 tsp 25 12 20 33 0.6 25
Rice 7 1 Tbsp + 2 tsp 25 17 17 34 0.6 27
Rice/apples 12 3 Tbsp 24 20 17 34 0.7 47
Rice/apple bits 10 2 Tbsp + 2 tsp 27 18 22 35 0.7 40
Rice/bananas 7 2 Tbsp 35 17 20 37 0.5 25
Rice/mixed fruit 9 2 Tbsp + 1-1/2 tsp 24 22 18 34 0.6 35
Cereals, Jarred
1st Foods ®
Oatmeal 36 2 Tbsp + 1-1/2 tsp 23 13 21 35 0.6 20
2nd Foods ®
Mixed/applesauce/bananas 74 5 Tbsp 26 15 17 35 0.7 64
Oatmeal/applesauce/bananas 56 4 Tbsp 27 12 12 35 0.7 46
Rice/applesauce 78 5 Tbsp + 1-1/2 tsp 26 20 15 35 0.6 71
3rd Foods ®
Mixed/apples/bananas 60 4 Tbsp 23 15 20 35 0.7 46
Oatmeal/apples/cinnamon 66 4 Tbsp + 2 tsp 26 15 19 35 0.7 44
Tender Harvest ™
Banana/oatmeal/peach 61 4-1/4 Tbsp 21 12 20 35 0.7 45
Butternut squash/corn 62 4 Tbsp + 1 tsp 29 19 20 35 1.2 31
Green beans/potatoes 28 2 Tbsp 27 15 23 35 0.6 18
Spring garden vegetables 64 4 Tbsp + 1-1/2 tsp 28 11 31 35 1.0 22
Vegetables
1st Foods ®
Peas 22 1 Tbsp + 1-1/2 tsp 29 9 31 35 0.7 11
Sweet potatoes 70 5 Tbsp 22 13 30 39 0.8 46
2nd Foods ®
Creamed corn 40 2-3/4 Tbsp 28 18 22 35 0.7 25
Creamed spinach 22 1 Tbsp + 1-1/2 tsp 31 16 26 35 0.7 10
Garden vegetables 35 2 Tbsp + 1-1/2 tsp 28 12 29 35 0.8 13
Peas 23 1 Tbsp + 1 tsp 29 9 31 35 0.7 11
Sweet potatoes 70 5 Tbsp 25 15 30 35 0.7 43

3rd Foods ®
Peas/rice 29 2 Tbsp 29 11 27 35 0.7 16
Sweet potatoes 54 3-3/4 Tbsp 25 13 28 35 0.5 32
Graduates ™
Mixed vegetables 42 ND 29 13 32 35 0.8 19
FRUITS/JUICES
1st Foods ®
Bananas 25 1 Tbsp + 2 tsp 7 5 7 15 0.3 25
Peaches 79 5 Tbsp + 1-1/2 tsp 11 6 11 15 0.6 34
Pears 115 8 Tbsp 12 9 12 15 0.5 66
Prunes 88 6 Tbsp 11 4 9 15 0.9 89
2nd Foods ®
Apples/pears 36 2 Tbsp + 1-1/2 tsp 9 5 8 15 0.3 30
Apricots/mixed fruit 79 5 Tbsp + 1-1/2 tsp 10 5 7 15 0.5 47
Bananas 25 1-3/4 Tbsp 10 5 7 15 0.3 22
Peach cobbler 150 10 Tbsp + 1-1/2 tsp 10 15 12 15 0.8 114
Peaches 79 5 Tbsp + 1-1/2 tsp 11 6 11 15 0.6 51
Pears 94 6 Tbsp + 1-1/2 tsp 11 6 8 15 0.5 70
Pear/pineapple 115 8 Tbsp 12 9 10 15 0.5 63
Plums/apples 125 8 Tbsp + 2 tsp 11 6 6 15 0.5 100
Prunes/apples 115 8 Tbsp 13 7 12 15 0.7 89
3rd Foods ®
Apricots/mixed fruit 79 5 Tbsp + 1-1/2 tsp 10 5 7 15 0.5 47
Bananas 25 1 Tbsp + 2 tsp 6 5 7 15 0.3 22
Banana/pineapple 34 2 Tbsp + 1 tsp 8 4 9 15 0.3 26
Banana/strawberry 32 2 Tbsp 8 4 6 15 0.3 30
Fruit salad 115 8 Tbsp 12 7 8 15 0.5 72
Hawaiian Delight dessert 23 1 Tbsp + 2 tsp 12 9 9 15 0.3 20
Peach cobbler 136 9 Tbsp + 1-1/2 tsp 11 12 11 15 0.7 105
Peaches 94 6 Tbsp + 1-1/2 tsp 11 8 12 15 0.7 60
Pears 94 6 Tbsp + 1-1/2 tsp 11 6 8 15 0.5 70
Plums/apples 73 5 Tbsp 7 3 7 15 0.3 50
Fruit Juice
Banana/strawberry juice medley 100 3-1/5 fl oz 12 11 10 15 0.4 58
Mixed 100 3-1/5 fl oz 11 11 10 15 0.3 48
Orange 200 6-1/4 fl oz 12 6 14 18 0.6 94
Tropical blend 100 3-1/5 fl oz 9 9 17 15 0.6 56
Fruit/Vegetable Juice
Apple/carrot 160 5 fl oz 8 5 10 14 0.3 69
Apple/sweet potato 115 3-2/3 fl oz 10 6 9 15 0.3 60
Tender Harvest ™
Apple/sweet potato 125 ND 11 5 14 15 0.4 79
Pear/wild blueberry 150 ND 24 5 8 15 0.6 92
Pears/winter squash 47 ND 12 8 10 15 0.5 24
Tropical fruit blend 52 ND 23 4 6 15 0.3 38
VEGETABLES
1st Foods ®
Carrots 67 1/4 cup + 2 tsp 15 7 15 20 0.6 23
Green beans 30 2 Tbsp 15 9 16 20 0.4 9
Potatoes 69 4 Tbsp + 2 tsp 22 10 14 35 0.7 32
Squash 53 3 Tbsp + 1 tsp 22 9 15 20 0.4 18
2nd Foods ®
Carrots 67 4 Tbsp + 2 tsp 15 7 15 20 0.5 20
Green beans 34 2 Tbsp + 1-1/2 tsp 15 7 15 20 0.4 10
Mixed vegetables 31 2 Tbsp 16 7 16 20 0.4 11
Squash 61 4-1/4 Tbsp 18 12 15 20 0.5 20
3rd Foods ®
Carrots 57 4 Tbsp 15 10 15 20 0.5 17
Green beans/rice 36 2 Tbsp + 1-1/2 tsp 15 9 14 20 0.4 15
Squash 77 5 Tbsp + 1 tsp 17 8 14 20 0.6 25
Vegetable Dices, Graduates ™

Carrots 53 ND 15 7 15 20 0.3 12
Green beans 28 ND 16 6 14 20 0.3 7
FREE FOODS A
Apple juice 163 5 fl oz 5 0 5 5 0.2 78

Apple/banana juice 65 2 fl oz 5 1 5 5 0.1 33
Apple/blueberry 62 4 Tbsp + 1-1/2 tsp 4 2 4 5 0.1 31
Apple/cherry juice 81 2-1/2 fl oz 4 1 5 5 0.2 39
Apple/cranberry juice 100 3.2 fl oz 4 1 5 5 0.1 44
Apple/grape juice 98 3 fl oz 2 0 3 5 0.1 48
Apple/prune juice 81 2-1/2 fl oz 4 1 5 5 0.2 43
Applesauce 57 1/4 cup 4 1 4 5 0.1 31
White grape juice 50 1-2/3 fl oz 4 0 4 5 0.3 30
Desserts, Tropical Fruit

Fruit medley 62 4 Tbsp + 1 tsp 3 1 2 5 0.1 40
Guava 71 1/3 cup 4 3 3 5 0.1 45
Mango 42 3 Tbsp 4 2 3 5 0.1 29
Papaya 83 5 Tbsp + 2 tsp 4 3 4 5 0.1 61
Fruit Dices, Graduates ™

Apples 100 ND 3 2 4 5 0.1 48
Mixed fruit 62 ND 3 2 4 5 0.2 30
Peaches 50 ND 4 3 4 5 0.2 35
Pears 56 ND 3 2 4 5 0.2 30
1
ND = No data.

Level Level
1 tsp = 1/3rd Tbsp = 4.8 g
1 Tbsp = 1/16th cup = 14.4 g
1/4 cup = 4 Tbsp = 57.3 g
1/3 cup = 5-1/3rd Tbsp = 76.3 g
1/2 cup = 8 Tbsp = 114.3 g
2/3 cup = 10 2/3rd Tbsp = 152.5 g
3/4 cup = 12 Tbsp = 171.5 g
1 cup = 16 Tbsp = 228.6 g

1
TABLE 13-4. Serving Lists for ILE-, MET-, THR- and VAL-Restricted Diets: Table Foods

BREADS AND CEREALS
Cereals, Cooked. Measure after cooking.

Cream of Rice 20 1/4 cup 9 16 27 35 0.5 32
Cream of Wheat
Mix'n Eat
plain 36 1/4 packet 30 13 22 34 0.7 26
flavored 38 1/4 packet 27 12 20 30 0.6 33
regular 38 2 Tbsp + 1-1/2 tsp 30 13 22 34 0.7 24
Farina 17 3 Tbsp + 1-1/2 tsp 32 13 22 35 0.7 25
Grits 15 3 Tbsp 25 15 23 33 0.6 27
Malt-o-Meal ® 15 3 Tbsp 31 13 21 33 0.7 23
Oats, regular, quick, and instant 22 1 Tbsp + 1-1/2 tsp 26 9 20 33 0.6 14
Wheatena ® 36 2 Tbsp + 1 tsp 32 13 22 35 0.7 20

All Bran ® 5 1 Tbsp 24 11 25 36 0.8 13
Alpha-Bits ® 8 1/4 cup + 1-1/2 tsp 27 11 21 35 0.6 31
Apple Jacks ® 13 1/2 cup 27 13 22 35 0.7 50
Bran, 100% 6 1 Tbsp + 1-1/2 tsp 25 11 25 36 0.8 17
Bran Buds ® 5 1 Tbsp 24 10 24 35 0.7 14
Bran Chex ® 7 2 Tbsp + 3/4 tsp 26 14 25 36 0.7 22
40% Bran Flakes (Post ®) 6 2 Tbsp + 3/4 tsp 25 10 22 35 0.7 19
Cap'n Crunch ® 13 5 Tbsp + 1-1/2 tsp 27 14 23 35 0.6 53
Cap'n Crunch's ® Crunch Berries 12 5 Tbsp + 1-1/2 tsp 27 14 22 34 0.6 51
Cap'n Crunch's ® Peanut Butter 9 1/4 cup + 3/4 tsp 26 11 21 35 0.6 40
Cheerios ® 4 3 Tbsp 30 11 22 38 0.6 17
Cinnamon Toast Crunch ® 29 3/4 cup 32 14 23 35 1.0 123
Cocoa Krispies ® 10 1/4 cup + 1-1/2 tsp 28 15 26 34 0.5 39
Cocoa Pebbles ® 12 1/4 cup + 2 Tbsp 29 16 28 35 0.6 50
Cocoa Puffs ® 21 3/4 cup 25 13 23 35 0.7 76
Cookie Crisp ® 13 1/4 cup + 3 Tbsp 27 13 22 35 0.7 52
Corn Bran ® 10 1/4 cup + 3/4 tsp 27 14 23 35 0.7 34
Corn Chex ® 10 5 Tbsp + 1 tsp 27 16 25 35 0.7 39
Corn Flakes ® 8 1/4 cup + 2 Tbsp 27 16 24 35 0.7 33
Crispy Wheat'n Raisins ® 11 1/4 cup 28 12 22 34 0.7 37
C W Post ®
plain 7 1 Tbsp 29 11 23 35 0.6 31
w/ raisins 7 1 Tbsp 27 10 22 35 0.6 28
Froot Loops ® 12 1/4 cup + 3 Tbsp 29 14 24 37 0.7 49
Frosted Mini-Wheats ® 7 1 square 29 13 24 36 0.7 25
Frosted Rice Krinkles 11 5 Tbsp + 1-1/2 tsp 29 16 27 35 0.5 43
Fruit Wheat Squares 14 2 Tbsp + 1-1/2 tsp 31 15 24 35 1.0 49
Fruity Pebbles ® 13 1/3 cup + 3-1/2 tsp 28 16 27 34 0.5 53
Golden Grahams ® 12 1/4 cup + 1 Tbsp 29 15 24 36 0.7 47
Granola (w/out nuts) 6 2-1/2 tsp 28 10 21 35 0.6 26
Grape Nuts 6 2-1/2 tsp 28 12 22 35 0.7 21
Grape Nut Flakes ® 7 3 Tbsp + 1 tsp 30 12 23 36 0.7 24
Heartland ®, plain 7 1 Tbsp 29 12 22 36 0.7 31
Honey Nut Cheerios ® 6 2 Tbsp + 1 tsp 27 11 22 34 0.6 21
Honey Nut Corn Flakes ® 11 1/4 cup + 1 Tbsp 28 14 26 35 0.8 47
Honeycomb ® 12 1/2 cup + 1 tsp 27 14 23 35 0.7 45
King Vitaman 13 9 Tbsp + 1-1/2 tsp 27 14 23 35 0.6 51
Kix ® 7 1/3 cup + 1 Tbsp 27 14 23 35 0.7 29

Life ® 3 1 Tbsp + 1/4 tsp 29 10 22 33 0.5 11
Lucky Charms ® 7 3 Tbsp + 3/4 tsp 29 10 22 35 0.6 27
Nutri-Grain ®
corn 9 3 Tbsp + 3/4 tsp 28 17 25 35 0.7 34
rye 8 3 Tbsp 28 10 24 34 0.7 27
wheat 9 3 Tbsp 33 14 23 35 0.8 32
Oat Flakes ® 3 1 Tbsp 31 11 27 35 0.6 11
Product 19 ® 8 3 Tbsp + 1-1/2 tsp 29 17 25 35 0.8 30
Quisp ® 13 1/4 cup + 3 Tbsp 28 14 23 35 0.7 54
Raisin Bran (Post ®) 9 2 Tbsp + 1-1/2 tsp 27 11 23 35 0.8 28
Rice, puffed 8 1/2 cup + 2 Tbsp 29 17 28 35 0.5 35
Rice Chex ® 10 1/3 cup + 1 Tbsp 28 15 26 35 0.5 39
Rice Krispies ® 8 1/4 cup + 1-1/2 tsp 29 16 28 35 0.5 32
Special K ® 3 1 Tbsp + 2-1/4 tsp 29 16 27 36 0.6 12
Sugar Corn Pops ® 14 7 Tbsp + 1-1/2 tsp 26 16 23 35 0.7 51
Sugar Frosted Flakes ® 14 1/3 cup + 1 Tbsp 27 16 24 35 0.7 52
Sugar Smacks ® 11 1/4 cup + 1-1/2 tsp 32 13 23 35 0.7 40
Super Sugar Crisp ® 12 5 Tbsp + 1-1/2 tsp 32 13 23 35 0.8 45
Team ® 9 3 Tbsp + 1-1/2 tsp 27 14 24 35 0.6 35
Total ® 7 3 Tbsp + 1-1/2 tsp 27 10 25 35 0.6 21
Trix ® 12 1/4 cup + 3 Tbsp 26 14 23 35 0.6 46
Wheat
germ
plain 2 1 tsp 25 13 28 34 0.7 9
w/ sugar 3 1-1/4 tsp 24 13 28 34 0.7 12
puffed 5 1/3 cup 31 13 23 35 0.7 18
shredded 7 1 Tbsp + 2-1/2 tsp 28 12 24 35 0.7 23
Wheat Chex ® 7 2 Tbsp + 1-1/2 tsp 30 13 22 34 0.7 26
Wheaties ® 7 1/4 cup 27 12 23 34 0.7 25
Grains
Corn
cob, medium 21 1/3 ear 26 14 26 37 0.6 19
cooked
cream style 11 2 Tbsp 22 12 22 32 0.6 23
whole kernel 17 1 Tbsp + 2 tsp 23 12 23 33 0.6 18
Rice, prepared
brown 25 2 Tbsp + 3/4 tsp 24 14 23 36 0.6 29
fried 21 1 Tbsp + 1-1/2 tsp 25 14 21 33 0.5 27
pilaf 19 1 Tbsp + 3/4 tsp 28 15 22 35 0.7 28
Rice-A-Roni ® 26 1 Tbsp + 2 tsp 28 15 23 35 0.8 33
Spanish 36 2 Tbsp + 1 tsp 25 13 22 35 0.6 31
white
instant 25 2 Tbsp + 1 tsp 24 13 20 34 0.6 27
regular 29 2 Tbsp + 3/4 tsp 25 14 21 36 0.6 32
Pasta, cooked
Macaroni 18 2 Tbsp + 1/2 tsp 31 16 24 35 0.9 26
Noodles, egg 15 1 Tbsp + 1-1/2 tsp 30 11 26 36 0.6 19
Ramen ® Noodles 17 1 Tbsp + 2 tsp 29 15 23 34 0.9 37
Spaghetti 18 2 Tbsp 32 16 25 37 0.9 27
Tubers
Potatoes, sweet
baked, in skin (mashed) 31 2 Tbsp + 1-1/2 tsp 27 13 27 35 0.5 32
boiled, no skin (mashed) 34 1 Tbsp + 2 tsp 28 14 28 37 0.6 36
canned, packed in syrup 20 1/4 cup + 1 Tbsp 27 13 26 35 0.5 84

Potatoes, white
baked, no skin 27 1/4 cup 27 10 23 35 0.6 29
boiled
no skin 36 3 Tbsp + 2 tsp 25 10 22 34 0.6 31
w/ skin 34 3 Tbsp + 1-1/2 tsp 26 10 23 36 0.6 30
French fries (1/2" x 1/2" x 2")
fresh 15 3 fries 26 7 28 31 0.6 47
frozen, baked 20 4 fries 31 8 32 36 0.7 65
hash browns, frozen, cooked 23 2 Tbsp + 1 tsp 31 8 33 37 0.7 50
salad 21 1 Tbsp + 1 tsp 30 14 24 36 0.6 30
Tater Tots ® 33 3-1/2 pieces 29 8 30 34 0.7 54
Yams, baked or boiled 20 1/4 cup + 3 Tbsp 30 12 31 36 0.9 69
Miscellaneous
Chow mein noodles 10 1/4 cup 32 13 22 35 0.8 58
Ice cream cone, wafer type 9 2, cone only 30 16 24 35 0.9 33
Snack Foods
Barnum's Animal Crackers ® 13 5 crackers 30 15 23 35 0.9 56
Breadsticks 8 1-1/4 sticks 31 16 25 36 0.9 29
Cookies
chocolate chip 15 1-1/4 cookies 31 12 24 35 0.8 77
fig bars 20 1-1/4 bars 38 10 21 34 0.8 72
gingersnaps 16 2-1/4 cookies 30 15 24 35 0.9 66
oatmeal raisin 11 3/4 cookie 28 14 23 35 0.7 48
Oreo ® 16 1-1/2 cookies 25 12 21 31 0.8 80
sandwich 17 1-1/2 cookies 27 14 22 32 0.8 82
Sno Balls ® 28 2/3 cookie 31 15 24 36 0.8 98
Social Tea Biscuits ® 16 3 biscuits 31 16 24 36 0.9 72
sugar (buttery) 13 1 cookie 27 14 21 32 0.8 55
Sugar Wafers (Nabisco ®) 22 4 wafers 28 14 22 32 0.9 107
vanilla wafers 16 4 wafers 30 15 23 35 0.9 74
Crackers
Goldfish ®, original 13 21 crackers 31 15 24 36 0.9 62
graham crackers (2" x 2") 11 1-1/2 crackers 29 15 23 34 0.8 40
Melba toast 6 1 piece 26 13 20 30 0.8 20
Ritz ® 13 4 crackers 30 15 23 35 0.9 66
Ritz Bits ®, cheese 8 11-1/2 crackers 31 15 22 35 0.8 40
Rykrisp ® 6 1 piece 27 11 24 34 0.6 23
saltines 9 3 crackers 28 14 22 33 0.8 39
Triscuits ® 9 2 crackers 26 13 20 30 0.8 42
Waverly ® 12 1-3/4 crackers 30 16 24 35 1.0 60
Wheat Thins ® 13 7 crackers 30 16 24 35 1.0 60
Ding Dongs ® 31 2/3 roll 29 13 25 36 0.9 144
Doodads ®, original 3 2 Tbsp + 1-1/2 tsp 30 14 25 35 0.9 44
Doritos ® 11 6 chips 24 11 24 35 0.8 53
Doughnut, cake 14 1/3 doughnut 33 11 22 33 0.6 54
Fritos ® 11 5-1/2 chips 26 12 26 35 0.7 60
Ho Ho's ® 21 3/4 roll 32 16 25 38 0.9 89
Marshmallow puffs 29 1-1/2 puffs 30 15 25 37 1.0 122
Popcorn
buttered 7 3/4 cup 27 16 24 35 0.7 31
caramel 4 1/4 cup + 1 Tbsp 27 16 24 35 0.7 42
plain 2 14 Tbsp + 1-1/2 tsp 27 17 24 36 0.7 21
Potato chips 10 5 chips 26 10 23 36 0.6 52
Pringles ® chips, 11 6 chips 25 9 22 34 0.6 62

Pretzels 6 1-1/4 pretzel 28 16 26 34 0.5 23
Twinkies ® 28 2/3 cookie 31 16 25 36 0.8 101
FATS
Gravy
beef, canned 2 1/2 tsp 4 2 4 4 0.1 1
brown, mix 1 2 tsp 4 2 3 5 0.1 3
chicken
canned 5 1 tsp 4 2 3 4 0.1 4
mix, dried 1 2 tsp 4 2 3 5 0.1 5
mushroom
canned 10 2 tsp 4 2 3 5 0.1 5
mix, dried 1 1 Tbsp 5 2 4 6 0.1 4
onion mix, dried 1 1 Tbsp 5 2 4 5 0.1 5
Margarine
imitation 5 1 Tbsp 5 2 3 5 0.1 50
soft 9 2 tsp 4 2 3 5 0.1 68
stick or brick 9 2 tsp 5 2 4 5 0.1 67
liquid 10 2 tsp 6 2 4 6 0.1 14
powder 1 3/4 tsp 4 2 3 5 0.1 8
Rich's ® Coffee Rich 36 2 Tbsp + 1-1/2 tsp 5 1 4 5 0.1 55
Polyrich ® 36 2 Tbsp + 1-1/2 tsp 5 1 4 5 0.1 55
Olives
black 10 2 olives 4 2 4 5 0.1 18
green 10 2 olives 5 2 4 6 0.1 12
Catalina 22 1/4 cup 5 1 6 5 0.3 290
French 13 2-1/2 tsp 4 2 4 5 0.1 56
Italian 16 3 Tbsp 4 2 4 5 0.1 65
Mayonnaise 7 1-1/2 tsp 5 2 4 5 0.1 50
Miracle Whip ® 21 1 Tbsp + 1-1/2 tsp 5 2 5 5 0.1 105
ranch 3 1/2 tsp 4 2 3 5 0.1 17
Russian 5 1 tsp 5 2 4 5 0.1 25
Thousand Island 8 1-1/2 tsp 4 2 4 4 0.1 29
tartar sauce 5 1 tsp 4 2 3 5 0.1 25
Cool Whip ®
extra creamy 3 2 tsp 5 2 4 5 0.1 10
regular 5 1 Tbsp + 3/4 tsp 4 2 3 5 0.1 14
Richwhip ®
pressurized 7 3 Tbsp 5 2 5 5 0.1 60
prewhipped 3 2 Tbsp 5 1 4 5 0.1 24
FRUITS
Apricots
canned, heavy syrup 27 1/4 cup + 1 Tbsp 13 2 15 15 0.4 67
dried
cooked, mashed 10 2 Tbsp 13 2 15 15 0.4 27
halves 11 3 12 2 14 14 0.4 25
nectar, canned 110 3-1/2 fl oz 12 2 15 15 0.4 61
whole 35 1 fruit 14 2 17 17 0.5 17
Avocados, all varieties, mashed 7 1 Tbsp + 1-1/2 tsp 15 8 14 21 0.4 35

Bananas, sliced 29 1/4 fruit 9 3 10 13 0.3 26
Blackberries
canned, heavy syrup 8 2 Tbsp + 1-1/2 tsp 12 1 16 15 0.5 37
frozen, sweetened 16 1/4 cup + 1 Tbsp 13 1 17 16 0.6 30
raw 72 1/2 cup 12 1 16 15 0.5 38
Blueberries
frozen, sweetened 29 1/4 cup + 2 Tbsp 10 5 10 15 0.3 70
raw 18 1/4 cup + 2 Tbsp 11 6 10 15 0.4 30
Cherries, canned, heavy syrup
sour, red 29 1/4 cup + 2 Tbsp 12 5 14 16 0.6 80
sweet 17 5 Tbsp + 1-1/2 tsp 12 5 14 15 0.6 36
Currants, black 8 3 Tbsp + 1-1/2 tsp 11 6 9 14 0.3 15
Dates, chopped 7 2 Tbsp 10 5 12 15 0.4 61
Figs
canned, heavy syrup 35 1/3 cup + 3-1/2 tsp 13 3 13 15 0.4 92
dried, uncooked, chopped 4 1 Tbsp 12 3 12 14 0.4 32
whole, large 50 1 fruit 12 3 12 14 0.4 37
Fruit cocktail, canned
heavy syrup 33 1/3 cup + 1 Tbsp 10 10 12 15 0.4 73
light syrup 31 1/4 cup + 2 Tbsp 9 9 11 15 0.4 54
Fruit salad, canned, heavy syrup 37 1/4 cup + 3 Tbsp 11 7 12 16 0.4 81
Gooseberry, canned, light syrup 18 3 Tbsp + 1-1/2 tsp 11 6 10 15 0.4 40
canned, light syrup 63 1/4 cup 10 1 6 15 0.4 38
juice, canned, unsweetened 185 6 fl oz 9 6 11 15 1.0 70
sections 57 1/4 cup 10 1 6 16 0.4 18
Grapes
Concord 92 1 cup 5 19 16 16 0.6 58
European, green 80 1/2 cup 4 18 14 14 0.5 57
juice 158 5 fl oz 11 2 25 16 0.9 96
Thompson, seedless, canned, heavy syrup 128 1/2 cup 5 20 17 17 0.6 93
Guavas
raw 59 2/3 fruit 18 3 18 17 0.5 30
sauce 17 1/4 cup + 1 Tbsp 16 3 16 14 0.4 26
Kiwi fruit 25 1/3 fruit 7 6 10 14 0.2 15
Mangoes, sliced 54 1/3 cup 10 3 10 14 0.3 35
Melons, cubed
cantaloupe 53 1/3 cup 15 3 13 15 0.5 18
Casaba 18 1/4 cup + 1 Tbsp 15 4 13 15 0.5 14
honeydew 35 1/2 cup + 2 Tbsp 15 3 14 15 0.5 37
Mixed fruit, canned, heavy syrup 84 1/3 cup 9 7 9 14 0.3 61
Nectarines 34 1/4 fruit 9 8 12 17 0.3 17
Oranges
juice
canned 156 5 fl oz 9 5 11 14 0.9 65
frozen, diluted 140 4 1/2 fl oz 10 4 11 15 0.9 63
sections 33 1/4 fruit 8 7 5 13 0.3 15
Papayas, cubed 140 1 cup 11 3 15 14 0.9 55
Peaches
canned, heavy syrup, sliced 64 1/4 cup 8 7 12 16 0.3 47
dried, chopped 8 1 Tbsp + 1-1/2 tsp 8 7 11 15 0.3 19
frozen, sweetened 16 3 Tbsp 8 7 11 16 0.3 44
nectar, canned 93 3 fl oz 8 7 9 14 0.3 50
sliced 42 1/4 cup 9 7 12 16 0.3 18
Pears
canned, heavy syrup 69 3/4 cup + 1 Tbsp 13 4 10 15 0.4 154
dried

cooked 16 3 Tbsp 12 5 11 15 0.4 61
halves 22 1-1/4 halves 12 5 11 14 0.4 57
sliced 38 1/2 cup + 3 Tbsp 13 6 11 16 0.4 67
Persimmons, Japanese 55 1/3 fruit 14 3 17 17 0.3 39
Pineapple 32 1/2 cup + 2 Tbsp 13 11 12 16 0.4 47
canned, heavy syrup 127 1/2 cup 12 12 12 14 0.4 99
juice, canned 156 5 fl oz 13 13 13 16 0.5 87
Plantain, cooked, sliced 24 7 Tbsp + 1-1/2 tsp 16 7 15 20 0.6 84
Plums
purple, canned, light syrup 166 2/3 cup 12 5 13 15 0.6 105
sliced 83 1/2 cup 13 5 13 16 0.7 45
Prunes
canned, heavy syrup 22 1/4 cup + 1-1/2 tsp 11 5 13 15 0.6 69
dried
cooked 53 1/4 cup 12 5 14 15 0.6 57
uncooked 21 2-1/2 fruits 11 5 12 14 0.5 50
juice, canned 96 3 fl oz 12 5 13 14 0.6 68
Raisins
golden 16 1 Tbsp + 2-1/4 tsp 4 18 15 15 0.5 48
regular, seedless 6 2 Tbsp 5 19 16 16 0.6 54
Raspberries
canned, heavy syrup 64 1/4 cup 12 1 16 15 0.5 58
frozen, red, sweetened 26 1/4 cup + 1 Tbsp 13 1 17 16 0.5 81
raw 61 1/2 cup 12 1 17 16 0.6 30
Rhubarb, cooked, sweetened 35 1/4 cup + 3 Tbsp 13 3 10 16 0.4 121
Strawberries
frozen, sweetened, sliced 34 1/3 cup + 1 Tbsp 12 1 16 15 0.5 97
raw, sliced 28 1/2 cup + 1 Tbsp 12 1 16 15 0.5 25
Tangerines
canned, light syrup 26 1/4 cup + 1 Tbsp 9 8 6 15 0.4 48
sections 55 2/3 fruit 9 7 6 15 0.3 24
Watermelon, cubed 32 9 Tbsp + 1-1/2 tsp 18 6 26 15 0.6 30
VEGETABLES
Asparagus, fresh or frozen, cooked 7 1-1/3 spears 19 5 14 20 0.5 5

Bamboo shoots, canned, sliced 11 1/4 cup + 1-1/2 tsp 17 6 17 21 0.5 4
Beans
snap green, canned 7 2 Tbsp + 2 tsp 14 5 17 19 0.4 7
sprouts, mung, seed attached to sprout 5 2 Tbsp + 1 tsp 20 5 12 20 0.5 5
yellow wax, canned 11 2 Tbsp 14 5 16 19 0.4 7
Beets, cooked
greens, chopped 9 3 Tbsp 14 6 21 21 0.7 7
red, fresh, canned, sliced 18 1/4 cup + 1 Tbsp 17 6 17 20 0.6 16
Broccoli, fresh or frozen, cooked 15 1 Tbsp + 1-1/2 tsp 17 5 14 20 0.4 4
Brussels sprouts, fresh or frozen, cooked 16 3/4 sprout 16 4 14 18 0.4 6
Cabbage
Chinese (Pak-choi)
cooked, cubed 11 3 Tbsp 28 3 16 22 0.5 4
raw, shredded 10 1/3 cup + 4 tsp 25 3 14 19 0.4 4
coleslaw 11 1/4 cup + 3/4 tsp 20 6 16 20 0.4 22
red, shredded
cooked 15 1/4 cup + 2 tsp 23 5 16 20 0.5 9
raw 11 7 Tbsp + 1-1/2 tsp 23 5 16 19 0.5 9

white, shredded
cooked 49 1/3 cup 24 5 16 20 0.5 10
raw 12 1/2 cup + 1-1/2 tsp 23 5 16 19 0.5 9
Carrots
cooked 43 1/4 cup + 1-1/2 tsp 18 3 17 20 0.5 20
sliced 46 1/3 cup + 1-1/2 Tbsp 19 3 17 20 0.5 20
Cauliflower
cooked 21 2 Tbsp + 2 tsp 15 5 14 19 0.4 5
raw 6 3 Tbsp 14 5 14 19 0.4 5
Celery, diced
cooked 33 10 Tbsp + 1-1/2 tsp 16 4 14 20 0.5 15
raw 26 10 Tbsp + 1-1/2 tsp 16 4 15 21 0.5 13
Chard, Swiss, cooked 6 1 Tbsp + 2 tsp 28 4 16 21 0.3 4
Chives 6 5 Tbsp + 1-1/2 tsp 20 5 18 21 0.5 4
Collards, fresh, cooked, chopped 12 3 Tbsp 16 5 14 19 0.4 5
Cucumber, pared, sliced 39 1 cup + 2 Tbsp 20 5 18 20 0.6 15
Eggplant, cubed
cooked 48 1/2 cup 17 4 14 21 0.4 13
raw 12 1/4 cup + 3 Tbsp 17 4 14 21 0.4 9
Endive, shredded 10 1/2 cup + 2 Tbsp 23 4 16 20 0.4 5
Kale, fresh, cooked 6 2 Tbsp + 1 tsp 22 3 16 20 0.4 6
Kohlrabi, cooked, sliced 12 3 Tbsp + 1-1/2 tsp 30 5 19 19 0.6 10
Leeks, diced
cooked 22 1/2 cup + 2 Tbsp 18 7 22 20 0.5 50
raw 12 5 Tbsp + 1-1/2 tsp 19 6 23 20 0.5 22
Lettuce, shredded
bibb 28 1/2 cup 33 5 17 19 0.4 4
iceberg 28 1/2 cup 21 4 15 17 0.3 4
leaf 28 1/2 cup 24 5 17 20 0.4 5
Romaine 8 1/3 cup + 3 tsp 25 5 17 20 0.4 4
Mushrooms, Agaricus bisporus, sliced
cooked or canned 8 1/4 cup + 2 tsp 18 8 20 20 0.4 5
raw 7 1/4 cup + 2 tsp 17 8 19 20 0.4 5
cooked 7 2 Tbsp + 1-1/2 tsp 18 5 13 19 0.5 3
raw 18 1/3 cup 8 5 13 19 0.5 5
Okra, cooked 8 2 Tbsp + 1 tsp 15 5 14 20 0.4 7
Onions
cooked 31 1/4 cup + 3 Tbsp 29 6 20 19 0.8 26
raw, diced 25 7 Tbsp + 1-1/2 tsp 32 8 21 20 0.9 26
rings, canned 30 1-1/3 cups 19 7 13 19 0.5 109
Parsnips, cooked 16 1/4 cup + 1 Tbsp 26 8 18 21 0.6 40
Peas, green
green, canned or frozen, cooked 8 2-1/2 tsp 16 7 17 19 0.4 7
pods (edible)
cooked 7 2 tsp 13 1 8 21 0.2 3
raw 8 2-1/2 tsp 12 1 7 21 0.2 3
w/ carrots 5 1 Tbsp + 1-1/2 tsp 17 7 17 20 0.5 7
Peppers
diced
cooked 25 1-1/2 cup + 1 Tbsp 15 6 18 20 0.5 14
raw 18 1/2 cup + 1-1/2 tsp 14 5 17 19 0.5 13
Jalapeño, canned, cooked 20 1/4 cup + 3 Tbsp 16 6 17 20 0.5 14
Pickles
dill
relish 30 1/3 cup + 3-1/2 tsp 20 50 17 20 0.6 17
whole, small 90 1-1/2 pickles 20 5 17 20 0.6 10

sweet
relish 125 1/2 cup 20 5 18 20 0.6 173
sliced 90 3 pieces 20 5 17 20 0.6 131
Pumpkin
canned 18 3 Tbsp + 1-1/2 tsp 18 7 17 20 0.6 18
pie mix (no eggs) 17 3 Tbsp 17 6 16 19 0.6 53
Radishes, red, sliced 58 1/2 cup 17 4 17 19 0.3 10
Rutabaga
cooked, mashed 15 1/4 cup + 3/4 tsp 21 4 20 20 0.5 15
raw, cubed 14 1/4 cup + 2 tsp 20 4 19 20 0.5 15
Sauerkraut 17 3 Tbsp + 1-1/2 tsp 24 5 16 20 0.5 10
Shallots, raw, chopped 7 2 Tbsp 21 5 20 22 0.5 14
Spinach, chopped
fresh or frozen, cooked 4 1 Tbsp 16 6 14 18 0.3 3
raw 4 3 Tbsp + 1-1/2 tsp 18 7 15 20 0.4 3
Squash,
fresh or frozen, cooked 16 1/4 cup + 3/4 tsp 16 6 11 20 0.4 10
sliced 13 1/4 cup + 2 tsp 16 6 11 20 0.4 8
winter, cubed
acorn, baked 14 3 Tbsp + 1 tsp 19 6 14 21 0.5 24
butternut, baked 51 1/4 cup 18 6 14 20 0.5 21
Hubbard, baked 10 1/4 cup + 3/4 tsp 18 6 14 20 0.8 16
spaghetti, boiled 77 1/2 cup 18 5 14 20 0.5 22
Tomatoes
catsup 10 2 Tbsp 19 22 21 19 0.6 33
juice 137 4 1/2 fl oz 21 6 23 21 1.0 23
paste 8 1 Tbsp + 1-1/2 tsp 18 5 21 19 0.9 21
purée 19 3 Tbsp + 2 tsp 18 5 22 19 1.0 23
sauce w/ onions, green pepper,& celery 24 1/4 cup + 2 tsp 19 5 21 19 0.9 21
stewed, canned 28 5 Tbsp + 3/4 tsp 18 7 19 20 0.8 22
whole, chopped 28 7 Tbsp + 1-1/2 tsp 18 7 19 19 0.8 16
Turnips
greens, cooked
chopped 9 3 Tbsp 16 7 17 21 0.3 5
w/ turnips, 5 1 Tbsp + 1-1/2 tsp 16 6 15 18 0.3 3
root, diced
cooked 29 1/2 cup + 1 Tbsp 26 8 18 20 0.6 16
raw 23 1/2 cup + 1 tsp 24 7 17 20 0.6 18
Vegetable Juice Cocktail (V-8 ® Juice) 167 5-1/2 fl oz 20 5 23 20 1.0 32
Vegetables, mixed 13 1 Tbsp + 1/2 tsp 19 5 15 20 0.4 8
Watercress, raw 5 1/3 cup + 4 tsp 13 3 19 19 0.3 2
Asparagus, Cream of 7 1 Tbsp + 1 tsp 16 7 13 19 0.4 14
Beef Broth 20 1 Tbsp + 1 tsp 20 12 20 22 0.5 3
Bouillon cubes
beef 2 2/3 cube 18 10 17 20 0.4 4
chicken 2 1/2 cube 18 9 15 17 0.4 5
Celery, Cream of 26 1 Tbsp + 2 tsp 16 6 12 19 0.3 19
Chicken
Broth 8 1-1/2 tsp 17 9 14 17 0.3 2
Cream of 16 1 Tbsp 21 10 16 22 0.4 15
Gumbo 21 1 Tbsp + 1 tsp 17 8 14 19 0.4 9
Noodle 5 1 Tbsp 19 9 16 21 0.5 9
Rice 10 2 tsp 15 8 12 16 0.3 5

Vegetable 5 1 Tbsp 17 8 14 20 0.5 9
Minestrone 5 1 Tbsp 16 6 13 22 0.5 10
Mushroom, Cream of 24 1 Tbsp + 1-1/2 tsp 18 7 15 20 0.4 24
Onion 26 1 Tbsp + 2 tsp 28 6 19 18 0.8 12
Potato, Cream of 26 1 Tbsp + 2 tsp 16 6 13 19 0.4 15
Scotch Broth 13 2-1/2 tsp 20 9 16 23 0.5 8
Split Pea W/ Ham 6 1 tsp 18 6 15 21 0.4 8
Tomato 13 2 Tbsp + 1-1/2 tsp 18 7 16 21 0.6 27
Tomato Bisque 10 2 Tbsp 19 7 16 21 0.6 30
Tomato Rice 12 2 Tbsp + 1 tsp 18 7 15 20 0.6 35
Vegetable
Beef 13 2 Tbsp + 1-1/2 tsp 18 7 16 21 0.6 27
Chunky, Ready To Serve 22 1 Tbsp + 1-1/2 tsp 15 3 10 18 0.3 11
Old Fashioned 23 1 Tbsp + 1-1/2 tsp 19 5 14 19 0.4 12
Vegetarian Vegetable 23 1 Tbsp + 1-1/2 tsp 19 5 14 19 0.4 14
FREE FOODS A
Beverages
Chocolate drink powder (Quik ®) 3 1 tsp 3 1 3 5 0.1 11
Juice
apple 248 8 fl oz 5 0 5 5 0.1 116
lemon 92 3 fl oz 4 2 5 6 0.4 19
lime 123 4 fl oz 4 1 4 5 0.3 26
tangerine 62 2 fl oz 3 1 4 5 0.3 31
Lemonade 508 16-1/2 fl oz 5 0 5 5 0.5 203
Nectar
papaya 173 5-1/2 fl oz 3 2 5 5 0.3 98
pear 125 4 fl oz 4 1 4 5 0.1 75
Desserts
Apple butter 9 1 Tbsp + 1 tsp 4 1 4 5 0.1 49
Chocolate
pudding mix 5 1-1/2 tsp 3 1 3 5 0.1 17
syrup (Hershey's ®) 5 3/4 tsp 3 1 3 5 0.1 10
Fruit bars, frozen
orange 24 1/3 bar 2 2 2 4 0.1 23
pineapple 37 1/2 bar 5 4 4 6 0.1 35
strawberry 74 1 bar 4 0 7 6 0.2 60
Fruit ice 9 2 Tbsp + 1 tsp 3 2 2 5 0.1 36
Fruit Roll-Ups ® 14 1 piece 4 1 5 5 0.2 55
Fun Fruits ® 51 2 pieces 4 2 2 5 0.2 200
Gelatin
dessert, prepared 15 1 Tbsp 3 2 4 6 0.2 9
pop 22 1/2 pop 4 2 4 6 0.3 16
Marshmallow 8 1 marshmallow 2 1 3 4 0.2 26
Marshmallow creme 21 1/4 cup + 3 Tbsp 4 3 3 5 0.6 198
Mocha Mix, frozen
chocolate 6 2 tsp 4 1 4 5 0.1 11
vanilla 8 1 Tbsp 5 1 4 5 0.1 17
M&M ®s, plain 1 1 piece 3 1 2 3 0.1 4
Raisins, chocolate covered 1 1 raisin 3 2 3 4 0.1 6
Sherbet, orange 6 1-1/2 tsp 4 2 3 5 0.1 8

Sorbet
peach 20 1 Tbsp + 1 tsp 3 2 4 5 0.1 20
pineapple 10 2 Tbsp 4 3 4 5 0.1 29
strawberry 15 3 Tbsp 4 0 5 5 0.3 43
Apples
canned w/ sugar 21 1/4 cup + 1 Tbsp 5 1 5 5 0.1 43
dried
cooked, chopped 4 2 Tbsp 4 1 4 5 0.1 26
uncooked 8 1/8 fruit 3 1 8 8 0.1 19
sauce
sweetened w/ sugar 64 1/4 cup 5 1 5 5 0.1 48
unsweetened 61 1/4 cup 4 1 4 5 0.1 26
whole 69 1/2 fruit 6 1 5 6 0.1 41
Cranberry sauce w/ sugar 20 3 Tbsp + 1-1/2 tsp 4 2 4 5 0.1 91
Fruit juice bar 52 1 bar 1 0 3 2 0.1 43
Guava sauce 15 3 Tbsp 5 1 5 5 0.1 16
Pie filling
apple 32 1/3 cup + 1 Tbsp 4 1 4 5 0.1 107
cherry 13 2 Tbsp + 1-1/2 tsp 4 2 4 5 0.2 41
peach 9 1 Tbsp + 2 tsp 3 2 3 4 0.1 30
Miscellaneous
Barbecue sauce 5 1 Tbsp 6 1 6 6 0.3 12
Butterscotch chips 2 3 chips 4 2 3 4 0.1 9
Chocolate frosting 8 1-1/2 tsp 3 1 3 5 0.1 32
Coconut, dried
sweetened w/ sugar 2 1-1/2 tsp 3 2 3 5 0.1 12
unsweetened 1 1/2 tsp 2 1 2 4 0.1 6
Cornstarch 11 3 Tbsp + 1-1/2 tsp 4 2 4 5 0.1 114
Honey 14 2 Tbsp 4 0 2 4 0.1 128
Horseradish 1 1-1/2 tsp 4 1 3 5 0.1 1
Jams and preserves 30 1 Tbsp + 1-1/2 tsp 4 0 5 5 0.2 81
Marmalade 8 1 Tbsp + 3/4 tsp 3 3 2 5 0.1 62
FREE FOODS B
These foods contain little or no ILE, MET, THR, or VAL. They may be used as desired if patient is not overweight and if they do not depress
appetite for prescribed foods.
Beverages
cola 123 4 fl oz 0 0 0 0 0.0 50
cream soda 124 4 fl oz 0 0 0 0 0.0 63
diet soda, sweetened w/ saccharine 118 4 fl oz 0 0 0 0 0.0 0
Dr Pepper ® 123 4 fl oz 0 0 0 0 0.0 50
ginger ale 122 4 fl oz 0 0 0 0 0.0 41
grape soda 124 4 fl oz 0 0 0 0 0.0 53
lemon-lime soda 123 4 fl oz 0 0 0 0 0.0 49
orange soda 124 4 fl oz 0 0 0 0 0.0 60
root beer 123 4 fl oz 0 0 0 0 0.0 50
Cranberry juice cocktail 127 4 fl oz 1 0 1 1 0.0 72
Exceed ® Energy Drink 124 4 fl oz 0 0 0 0 0.0 35
Fruit drink (Hi-C ®) 124 4 fl oz 0 0 0 0 0.0 58
Fruit juice drink 124 4 fl oz 0 4 3 3 0.1 62
Gatorade ® Thirst Quencher 121 4 fl oz 0 0 0 0 0.0 30
Kool-Aid ®, sweetened w/ sugar 123 4 fl oz 0 0 0 0 0.0 49
Orange drink powder (Tang ®) 16 1/4 cup 1 0 1 1 0.0 187
Strawberry drink powder (Quik ®) 3 1 Tbsp 0 0 0 0 0.0 33
Desserts/Sweeteners
Candies
candy corn 16 10 pieces 0 0 0 0 0.0 58
gumdrops 20 10 pieces 0 0 0 0 0.0 69
hard candy 15 3 pieces 0 0 0 0 0.0 58
jelly beans 17 6 pieces 0 0 0 0 0.0 62
Jellies 20 1 Tbsp 0 0 0 0 0.0 54
Popsicle ®, twin 128 1/2 popsicle 0 0 0 0 0.0 95
Pudding
lemon, canned (Hunt's ®) 121 1 container 0 0 0 0 0.0 151
vanilla mix, dried 4 1 Tbsp 0 0 0 0 0.0 40
Tapioca, dry 10 1 Tbsp 1 1 1 2 0.1 36
Miscellaneous
Frosting
vanilla 16 1 Tbsp 0 0 0 0 0.0 69
Molasses 7 1 Tbsp 0 0 0 0 0.0 48
Oil, vegetable (except olive) 14 1 Tbsp 0 0 0 0 0.0 120
Richwhip ® liquid 5 1 Tbsp 0 0 0 0 0.0 40
Salad dressing, oil/vinegar 5 1 Tbsp 0 0 0 0 0.0 70
Shortening 4 1 Tbsp 0 0 0 0 0.0 113
Sugar
brown 14 1 Tbsp 0 0 0 0 0.0 52
powdered 3 1 Tbsp 0 0 0 0 0.0 31
table 12 1 Tbsp 0 0 0 0 0.0 48
Syrup
corn 20 1 Tbsp 0 0 0 0 0.0 58
maple 20 1 Tbsp 0 0 0 0 0.0 50
table 7 1 Tbsp 0 0 0 0 0.0 50
1
See Appendix 12, p A-11, for Nutrient Composition of very low protein foods.

TABLE 13-5. Propionic Acidemia or Methylmalonic Acidemia Clinical Summary Sheet
258 Propionic Acidemia/Methylmalonic Acidemia
Date of Birth: __________/__________/__________ Age at Diagnosis: ____

Mo Day Year

1 1 1 1 1
Length/ Weight Head ILE MET THR VAL GLY Free Organic Ferritin Hgb Hct Trans-thyretin ILE MET THR VAL Protein Energy
Height Circum Carnitine Acids (mg/dL)
(mo/d/yr) (yrs/mo) (cm) (kg) (cm) (µmol/L) (ng/mL) (g/dL) (%) (mg) (mg) (mg) (mg) (g) (kcal)
1 Indicate if µmol/L or mg/dL.

REFERENCES
1985, 115-135.
2. Al-Essa M, Rahbeeni Z, Jumaah S, et al: Infectious complications of propionic acidemia in Saudi Arabia. Clin
Genet 1998;54:90-94.
Dis 2000;23 Suppl 1:29A.
4. Baumgartner ER, Viardot C: Long-term follow up of 77 patients with isolated methylmalonic acidaemia. J Inher
Metab Dis 1995;18:138-142.
1996.
6. Burlina AB, Dionisi-Vici C, Piovan S, et al: Acute pancreatitis in propionic acidaemia. J Inher Metab Dis
1995;18:169-172.
7. Chalmers RA, Stacey TE, Tracey BM, de Sousa D C: L-carnitine insufficiency in disorders of organic acid
metabolism. Response to L-carnitine by patients with methylmalonic acidemia and 3-hydroxy-3-methylglutaric
acidemia. J Inher Metab Dis 1984;7 (Suppl 2):109-110.
8. Ciani F, Poggi GM, Pasquini E, et al: Prolonged exclusive breast-feeding from vegan mothers causing an acute
onset of isolated methylmalonic aciduria due to mild mutase deficiency. Clin Nutr 2000;19:137-139.
9. Coude FX, Ogier H, Grimber G, et al: Correlation between blood ammonia concentration and organic acid
accumulation in isovaleric and propionic acidemia. Pediatrics 1982;69:115-117.
10. Dechaux M, Touati G, Vargas-Poussou R, et al: Renal function and follow-up in children with methylmalonic
acidemia. J Inher Metab Dis 2000;23 (Suppl 1):97 (Abs).
11. DeRaeve L, De-Meirleir L, Ramet J, et al: Acrodermatitis enteropathica-like cutaneous lesions in organic acidemia.
J Pediatr 1994;124:416-420.
13. Fenton WA, Gravel RA, Rosenblatt DS: Disorders of propionate and methylmalonate metabolism. In Scriver CR,
et al (eds): The Metabolic and Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical
Publishing Division, 2001, pp 2165-2194.
concentrations. JPEN 1991;15:48-53.
16. Haas RH, Marsden DL, Capistrano-Estrada S, et al: Acute basal ganglia infarction in propionic acidemia. J Child
Neurol 1995;10:18-22.
17. Hamilton RL, Haas RH, Nyhan WL, et al: Neuropathy of propionic acidemia: A report of two patients with basal
ganglia lesions. J Child Neurol 1995;10:25-30.
18. Henriquez H, el-Din A, Ozand PT: Emerging presentations of patients with methylmalonic acidemia, propionic
acidemia and branched-chain amino acidemia (MSUD). Brain Development 1994;16:86-93.
mixture and different amounts of single dose ingested. A case report. Eur Pediatr 1994;153:501-503.
20. Inoue S, Kreiger I, Sarnaik A, et al: Inhibition of bone marrow stem cell growth in vitro by methylmalonic acid: A
mechanism for pancytopenia in a patient with methylmalonic acidemia. Pediatr Res 1981;15:95-98.
22. Kahler SG, Millington DS, Cederbaum SD, et al: Parenteral nutrition in propionic and methylmalonic acidemia.
J Pediatr 1989;115:235-241.
23. Kahler SG, Sherwood WG, Woolf D, et al: Pancreatitis in patients with organic acidemias. J Pediatr
1994;124:239-243.
24. Kalloghlian A, Gleispach H, Ozand PT: A patient with propionic acidemia managed by continuous insulin infusion
and total parenteral nutrition. J Child Neurol 1992;7 (Suppl):S88-S91.
25. Leonard JV: The management and outcome of propionic and methylmalonic acidemia. J Inher Metab Dis
1995;18:430-434.
1982.
1987;1:1-17.
28. Massoud AF, Leonard JV: Cardiomyopathy in propionic acidaemia. Eur J Pediatr 1993;152:441-445.
29. Mellon AP, Deshpande SA, Mathers JC, Bartlett K: Effect of oral antibiotics on intestinal production of propionic
acid. Arch Dis Child 2000;82:169-172.

30. North KN, Korson MS, Gopal YR, et al: Neonatal onset propionic acidemia: Neurologic and developmental profiles,
and implications for management. J Pediatr 1995;126;916-922.
31. Ogier de Baulny H, Saudubray JM: Branched-chain-organic aciduria. In Fernandes J, et al (eds): Inborn Metabolic
Diseases. Diagnosis and Treatment ed 3. New York: Springer-Verlag, 2000, pp 196-212.
33. Petrowski S, Nyhan WL, Reznik V, et al: Pharmacologic amino acid acylation in the acute hyperammonemia of
propionic acidemia. J Neurogenet 1987;4:87-96.
35. Praphanphoj V, Brusilow S, Hamosh A, Geraghy MA: The use of intravenous sodium benzoate and sodium
phenylacetate in propionic acidemia with hyperammonemia. J Inher Metab Dis 2000;23 (Suppl 1):91 (Abs).
1955;56:231-251.
37. Raby RB, Ward JC, Herrod HG: Propionic acidaemia and immunodeficiency. J Inher Metab Dis 1994;17:250-251.
38. Rose WC, Wixon RL, Lockhart HB, Lambert GF: The amino acid requirements of man. XV. The valine
requirements: Summary and final observations. J Biol Chem 1955;217:987-995.
39. Roth B, Younossi-Hartenstein A, Skopnik H, et al: Hemodialysis for metabolic decompensation in propionic
acidaemia. J Inher Metab Dis 1987;10:147.
40. Rutledge SL, Geraghty M, Mroczek E, et al: Tubulointerstitial nephritis in methylmalonic acidemia. Pediatr Nephrol
1993;7:81-82.
41. Saudubray JM, Touati G, Delonlay P, et al: Liver transplantation in propionic acidemia. Eur J Pediatr
1999;158 (Suppl 2: S65-S69).
42. Sbai D, Narcy C, Thompson GN, et al: Contribution of odd-chain-fatty acid oxidation to propionate production in
disorders of propionate metabolism. Am J Clin Nutr 1994;59:1332-1337.
43. Schoeffer A, Herrmann ME, Broesicke GH, Moench E: Effect of dosage and timing of amino acid mixtures on
44. Sequeira JSS, Dixon MA, Leonard JV: Growth in disorders of propionate metabolism. J Inher Metab Dis
1996;19 (Suppl):44 (Abs).
45. Shafai T, Sweetman L, Weyler W, et al: Propionic acidemia with severe hyperammonemia and defective glycine
metabolism. J Pediatr 1978;92:84-86.
46. Shapiro LJ, Bocian ME, Raijam L, et al: Methylmalonyl-CoA mutase deficiency associated with severe neonatal
hyperammonemia activity of urea cycle enzymes. J Pediatr 1978;92:986-988.
47. Smith CA, Nelson NM: The Physiology of the Newborn Infant, ed 4. Springfield, Ill: Charles C Thomas Publisher,
1976.
1983;7:280-288.
Clin Nutr 1964;15:313-321.
Clin Nutr 1964;15:322-330.
1959;97:186-191.
53. Snyderman SE, Holt LE, Norton PM, et al: The plasma aminogram. I. Influence of the level of protein intake and a
comparison of whole protein and amino acid diets. Pediatr Res 1968;2:131-144.
1989;143:828-832.
55. Stork LC, Ambruso DR, Wallner SF, et al: Pancytopenia in propionic acidemia: Hematologic evaluation and
studies of hematopoiesis in vitro. Pediatr Res 1986;20:783-788.
56. Stumpf DA, Parker WD, Engelini C: Carnitine deficiency, organic acidemias and Reye's syndrome. Neurology
1985;35:1041-1045.
57. Sugiyama N, Matsuda I, Wada Y, et al: Urinary propionylcarnitine analysis for monitoring carnitine
supplementation in inherited disorders of propionate metabolism. J Inher Metab Dis 1994;17:611-615.
58. Thompson GN, Bresson JL, Bonnefont JP, et al: A simple isotopic technique for assessing vitamin responsiveness
in vivo in propionic acidaemia. J Inher Metab Dis 1990;13:3413-351.
59. Thompson GN, Walter JH, Bresson JL: Sources of propionate in inborn errors of metabolism. Metabolism
1990;39:1133-1137.
60. Thompson GN, Chalmers RA: Increased urinary metabolic excretion during fasting in disorders of propionate
metabolism. Pediatr Res 1990;27:413-416.
61. Tietz NW (ed): Textbook of Clinical Chemistry. Philadelphia: WB Saunders Company, 1986.

62. Tornqvist K, Tornqvist H: Corneal deepithelialization caused by acute deficiency of isoleucine during treatment of a
patient with maple syrup urine disease. Acta Ophthalmol Scand 1996;74 (Suppl 219):48-49.
63. van Calcar SC, Harding CO, Davidson SR, et al: Case reports of successful pregnancy in women with maple
syrup urine disease and propionic acidemia. Am J Med Genet 1992;44:641-646.
64. van der Meer SB, Poggi F, Spada M, et al: Clinical outcome and long term management of 17 patients with
propionic acidemia. Eur J Pediatr 1996;155:205-210.
65. van't Hoff W, McKiernan PJ, Surtees RAH, Leonard JV: Liver transplantation for methylmalonic acidemia. Eur J
Pediatr 1999;158 (Suppl 2):S70-S74.
66. van't Hoff WG, Dixon M, Taylor J, et al: Combined liver-kidney transplantation in methylmalonic acidemia.
J Pediatr 1998;132;1043-1044.
1977;30:1269-1280.
68. Wendel U, Eibler A, Speir W, Schadewaldt P: On the differences between urinary metabolite excretion and odd-
numbered fatty acid production in propionic and methylmalonic acidaemias. J Inher Metab Dis 1995;18:584-591.
69. Wolf B: Reassessment of biotin-responsiveness in "unresponsive" propionyl-CoA carboxylase deficiency. J Pediatr
1980;97:964-966.
70. Worthen HG, Ashwal AA, Ozand PT, et al: Comparative frequency and severity of hypoglycemia in selected
organic acidemias, branched-chain amino acidemia, and disorders of fructose metabolism. Brain Dev
1994;16 (Suppl);81-85.
71. Yannicelli S: Nutrition support of methylmalonic acidemia. Metabolic Currents. 1988;1:10-13.
72. Young VR, Tontisirin K, Ozalp I, et al: Plasma amino acid response curve and amino acid requirements in young
men: Valine and lysine. J Nutr 1972;102:1513-1170.

PROTOCOL 14 — Galactosemia

ISOMIL ® Soy Formula Powder With Iron
I. Introduction
Galactosemia is an inherited disorder of galactose (GAL) metabolism that results from a defect in one of
three enzymes: galactokinase, GAL-1-phosphate uridyltransferase (GALT), and uridine diphosphate
(UDP)-GAL-4-epimerase (Figure M). The most common form of galactosemia results from a defect in
GALT activity. Its estimated incidence is 1/40,000 to 1/80,00 live births. Patients with GALT deficiency
appear normal at birth, but soon develop severe hepatic, renal, and gastrointestinal manifestations
which, if not treated, lead to death (36, 37, 71). Symptoms may include cataracts, diarrhea, E coli
sepsis, failure to thrive, jaundice, vomiting, and increased intracranial pressure. Patients with
galactokinase deficiency present with cataracts secondary to accumulation of galactitol in eye lenses
(70). Galactonate accumulates in erythrocytes of patients with GALT deficiency and, if cellular redox
potential is altered, may contribute to GAL toxicity (8, 80). Removal of dietary lactose and GAL is
essential to prevent further metabolic crises in patients with GALT deficiency. Rapid screening,
retrieval, diagnosis, and treatment are essential to prevent clinical manifestations.
Galactosemia due to a deficiency in GALT leads to an accumulation of GAL-1-phosphate (GAL-1-P)
and galactitol in erythrocytes, liver, kidney, brain, and other tissues (17, 70). Additional laboratory
findings include albuminuria, hypophosphatemia, hypokalemia, and hyperaminoaciduria.
Reasons for symptoms associated with GALT deficiency are not well defined but may be due to
involvement of GAL-1-P in a futile phosphorylation cycle and reduced ATP, CTP, and GTP. Other
proposed hypotheses include defective GAL incorporation into galactosylated compounds (14, 62, 66,
75).
Reductase Oxidase
Galactitol Galactose Galactonate
ATP
Galactokinase
ADP
P~P UTP
Galactose-1-P*
UDP - Galactose
Pyrophosphorylase
UDP - glucose
GALT
Epimerase UDP - galactose
Site of enzyme defects that Glucose-1-P

lead to galactosemia
* Accumulates in untreated galactosemia
Glycolytic pathway
Figure M. Metabolism of GAL in galactosemia

If untreated, patients with GALT deficiency usually die of overwhelming sepsis (48). Early intervention
with a GAL-restricted diet is successful in preventing death and reducing the risk for cataracts. For
years, clinicians considered that patients who were diagnosed and treated early would develop
normally.
© 2001 Ross Products Division Galactosemia 267

Komrower and Lee (44) in 1970 first reported neurologic impairment in early treated patients with
galactosemia. Subsequent studies suggest that management has resulted in suboptimal clinical
outcomes (22, 43). A report by Waggoner and coworkers based on survey data, presented the
outcome of 350 children and adults with GALT deficiency (76). The patients showed a decline in IQ
with age, delayed and deficient speech development (76), and stunted growth, especially in females.
Surprisingly, no correlation was found between reduced IQ, age at onset of therapy or erythrocyte
GAL-1-P concentrations.
Hypogonadotropic hypogonadism and infertility have been reported in most females with
galactosemia (40). Hypogonadism with reduced calcium intake results in reduced bone density in
prepubertal and postpubertal patients. Calcium intake correlated positively with bone density (41).
Multiple mutations in the GALT gene have been identified (21). Patients with the Q188R mutation,
prevalent among Caucasians, have poorer outcomes than patients with the S135L mutation, which is
common in African-American patients with galactosemia (45). Despite the apparent correlation
between genotype and phenotype, genotype alone has not answered all the questions regarding
outcome (15, 21, 42, 72).
Several theories have been proposed to explain the poor outcomes in patients with galactosemia.
These theories include fetal damage in utero, damage before nutrition intervention, over-restriction or
inadequate restriction of dietary GAL, de novo GAL synthesis (7), and a deficiency of UDP-GAL (17,
51, 58).
More questions than answers regarding optimal treatment to alleviate the clinical manifestations
associated with GALT deficiency still abound. Further research may lead to modifications in nutrition
support. Oral uridine therapy has not been beneficial despite normalization of erythrocyte UDP-GAL
concentrations (51, 59).

A. The Defect
1. Galactosemia may result from defect in any 1 of 3 enzymes:
a. Galactokinase.
b. GALT.
c. UDP-GAL-4-epimerase (37).
B. Screening
1. A positive result on newborn galactosemia screening requires differential diagnosis.
2. Because not all states screen for galactosemia, infants with the following clinical findings
should be evaluated for galactosemia (9, 19, 37, 71):
a. Prolonged jaundice.
b. Vomiting and/or diarrhea.
c. Failure to thrive.
d. Hepatomegaly.
e. Sepsis caused by E coli.
f. Cataracts.
3. Infants with abnormal results on newborn screening and/or above signs and symptoms should
be switched to lactose-free infant formula such as Isomil powder.
2. Therapy depends on enzyme defect and residual enzyme activity present.
3. This protocol addresses nutrition support for patients with galactokinase and GALT
deficiencies.

1. Remove or restrict dietary GAL to lowest amount compatible with nutritionally adequate diet.
B. Chronic GAL Toxicity Theory
1. Of theories regarding poor outcomes in patients with GALT deficiency, chronic GAL toxicity
has recently been supported by finding arabinogalactans, galactans (ß-1-4-linkages),
galactolipids, and galactoproteins in cereals, fruits, legumes, nuts, and vegetables (1, 2, 5, 11,
268 Galactosemia © 2001 Ross Products Division

12, 16, 18, 25-27, 47, 49, 52-54, 56, 64, 68, 69, 74, 79, 81) and free GAL in fruits, legumes,
seeds, and vegetables (1, 13, 28-35, 39, 55, 61, 67).
2. Enzymes in intestinal juices and from the pancreas are capable of digesting several forms of
GAL in ß-1-4 linkage (3, 4)

A. Growth, Development, and Nutrition Status
in adults.
2. Support normal development (20, 37, 71, 72).
B. Galactokinase Deficiency
1. Maintain blood and urine free of GAL and galactitol.
2. Prevent cataracts.
C. GALT Deficiency and Variants With < 35% Enzyme Activity (65)
1. Maintain 2 to 4 hour postprandial erythrocyte (RBC) GAL-1-P concentration < 2 mg/dL (17) or
< 20 µg/g hemoglobin (65).
2. Attempt to reduce blood and urine galactitol to acceptable concentrations (63, 82).
a. Urinary galactitol does not always correlate with RBC GAL-1-P concentration (70).
3. Prevent mental retardation and abnormal speech (76, 77).
4. Prevent neurologic deterioration (10, 24, 50, 57, 70).
5. Reduce risk of ovarian failure in women (40).

A. GAL
1. Remove foods and do not use drugs (45) containing free GAL, lactose, and bound GAL that
may be released by α- and ß-galactosidases.
B. Protein
1. Recommended protein intakes are same as for normal infants, children, and adults
(Table 14-1, p 269).
C. Energy
1. Recommended energy intakes are same as for normal infants, children, and adults
(Table 14-1, p 269).
2. Intakes should be sufficient to maintain normal weight gain for infants and children and
maintain appropriate weight for height for adults.
D. Fluid
2. Requirements may be higher than recommended secondary to accompanying fever.

A. GAL
1. See Table 14-2, p 270, for foods allowed, foods excluded, and foods that may be limited.
a. For more information on nutrient content of beikost (baby foods), contact the following
manufacturers:
Beech-Nut Nutrition Gerber Products Company Heinz North America
Corporation c/o Consumer Affairs Consumer Affairs
100 S 4th Street 445 State Street USX Tower
St Louis, MO 63102 Fremont, MI 49413-0001 600 Grant Street, 7th Floor
1-800-233-2468 1-800-443-7237 Pittsburgh, PA 15219
1-800-872-2229

b. Up-to-date lists of product ingredients are necessary to determine which foods may be
included since ingredients change often.
c. Exclude foods containing one or more ingredients excluded in Table 14-2, p 270.
B. Protein
1. Calculate amount of Isomil ® Soy Formula With Iron powder, beikost, or table foods
a. Protein intakes up to 2.0 times greater than Recommended Dietary Allowances (RDAs)
(23) are not cause for concern if liver function is normal.
Warning: ALL LIQUID SOY PROTEIN ISOLATE INFANT FORMULAS MANUFACTURED
IN THE US CONTAIN CARRAGEENAN WHICH CONTAINS 27% GAL.
2. Add beikost or table foods to provide variety in taste, color, and texture after infant is 3 to
4 months old or is developmentally ready (Table 14-3, p 274).
C. Energy
1. Calculate energy provided by Isomil powder, beikost, or table foods (Table 14-3, p 274)
required to fill protein prescription.
2. If energy prescription is not met, increase number of food servings or increase volume or
concentration of Isomil.
3. Isomil may be concentrated to 24 or 27 kcal/fl oz if additional energy is required and volume
cannot be increased.
4. To make formula with 24 or 27 kcal fl oz from Isomil powder, follow the directions below:
Isomil Powder Add Water to Make
(g) (scoops)
24 kcal/fl oz 157 18 1 L (34 fl oz)
27 kcal/fl oz 177 20 1 L (34 fl oz)
D. Fluid
1. Mix Isomil powder according to label directions to obtain a formula that provides 20 kcal/fl oz.
2. Offer infants additional fluid ad libitum between Isomil feeds if > 20 kcal/fl oz is used.
E. Diet Guide
each diet change.

2. Check diet to determine if it supplies Recommended Daily Nutrient Intakes of protein and
energy (Table 14-1, p 269).
a. See Appendix 5, p A-5, for composition of Isomil.
not available.
c. If diet provides < 100% of RDIs for infants and < 75% for children and adults, supplement
diet with needed minerals and vitamins if not provided by beikost or table foods and
Warning: Calcium supplements are often required by children and adults with
galactosemia (60, 73).
B. Osmolarity
b. Osmolarity per gram of Isomil powder is listed in Appendix 19, p A-21.

mixture and recalculate its osmolarity.
renal solute load.
recalculate.

A. Galactokinase Deficiency
1. Evaluate urine GAL and galactitol concentrations weekly until patient is 6 months old, every
2 weeks until patient is 1 year old, and monthly thereafter if concentrations remain elevated.
a. If GAL or galactitol is present in unacceptable concentrations (urine GAL > 140 mmol/mol
creatinine; urine galactitol > 31 mmol/mol creatinine) (62, 81) obtain diet history and
review diet records for use of excluded or limited foods (Table 14-2, p 270).
1) If excluded foods have been used, instruct parents or patients to remove them from
diet.
2) If GAL or galactitol is still present after removal of excluded foods from diet, instruct
parents or patients to remove limited foods.
3) Call food and drug manufacturers to determine if any processed foods or drugs used
contain added GAL or lactose.
B. GALT Deficiency
1. Evaluate blood for GAL and erythrocyte GAL-1-P concentrations weekly until patient is
6 months old, every 2 weeks until patient is 1 year old, and monthly thereafter.
a. If erythrocyte GAL-1-P is > 2 mg/dL or 20 µg/g hemoglobin, obtain diet history and review
diet records for use of excluded or limited foods (Table 14-2, p 270).
1) If excluded foods have been used, instruct parents or patients to remove them from
diet.
2) If GAL is still present or erythrocyte GAL-1-P is still elevated after removal of
excluded foods from diet, instruct parents or patients to remove limited foods.
3) Call food and drug manufacturers to determine if any processed foods or drugs used
contain added GAL or lactose.
2. Evaluate urine GAL and galactitol concentrations at same time erythrocyte GAL-1-P
concentration is evaluated.
C. Galactokinase and GALT Deficiencies
1. Protein status.
a. Evaluate plasma albumin concentration every 6 months until patient is 1 year old and
b. If plasma albumin concentration is below standard:
1) Increase prescribed amount of protein by 5% to 10% and reevaluate plasma albumin
2) If plasma albumin concentration remains below standard, repeat above process until
2. Iron status.
a. Plasma ferritin concentration.
1) Evaluate at 6, 9, and 12 months of age and every 6 months thereafter (Appendix 17,
2) If plasma ferritin concentration is below standard:
i. Increase iron intake to 2 mg/kg with supplements (ferrous sulfate).

ii. Evaluate plasma ferritin concentration monthly on increased iron intake.
iii. Continue iron supplements until plasma ferritin concentration is in normal range.
b. Complete blood count.
1) Evaluate hemoglobin and hematocrit concentrations at 6, 9, and 12 months of age
and every 6 months thereafter (Appendix 17, p A-18, for standards).
3. Growth status.
a. Length/height and weight.
1) Measure monthly to 1 year, every 3 months to 4 years, and every 6 months thereafter.
2) Maintain length/height and weight between 10th and 90th percentiles. Some normal
3) If length/height or weight falls below usual growth channel:
i. Increase prescribed protein and energy by 5% to 10% and remeasure in 1 month.
ii. If length/height or weight remains low, repeat above process until usual growth
channel is achieved.
4. Nutrient intake.
a. Maintain records of food intake for 3 days immediately before each blood test
(Appendices 24 and 25, pp A-26 and A-27).
b. Evaluate intakes of protein and energy before each blood test.
c. Evaluate mineral and vitamin intakes after each diet change.
1) Appendix 23, p A-25, may be used to check adequacy of nutrients if computer
program is not available.
2) See Appendix 28, p A-29, for information about ordering software for diet evaluation.
3) If supplements are recommended, contact manufacturer for confirmation that
supplements are lactose- and GAL-free.
Warning: Serum calcium does not reflect dietary calcium intake. DO NOT use
Neocalglucon ® as calcium supplement since it contains GAL (33).
5. Clinical summary.
a. A summary record of growth, laboratory, and nutrient intake data is useful for patient
A. Example 1
Establish and fill prescription for newborn who weighs 3.5 kg using Recommended Daily
Nutrient Intakes from Table 14-1, p 269, and average nutrient contents from Table 14-3, p
274.
(g) (kcal)
Isomil powder mixed to 20 kcal/fl oz 618 mL 10.2 420
(21 fl oz)

is < 100 mosm.

A. Rationale
1. In normal persons, febrile illness and trauma are accompanied by catabolism of body protein
(78).

2. Well-nourished patients with galactosemia respond to infection and trauma as do normal
persons .
Jell-O ®; Polycose Glucose Polymers powder or liquid (Appendix 9, p A-9), or Pro-Phree
® Protein-Free Energy Module With Iron, Vitamins & Minerals (Appendix 11, p A-10)
added to fruit juices or Pedialyte if tolerated and caffeine-free soft drinks (not diet drinks).
b. Return patients to Isomil as rapidly as possible.
1) Begin with 1/2 original strength of Isomil formula.
XII. Prescription and Over-The-Counter Medications

A. Contact a local pharmacist or drug manufacturer for current information on excipients in drugs that
may contain GAL (44).
Warning: Neocalglucon, a liquid calcium supplement available only by prescription,
contains GAL and should not be used (33).
1. Most tablets of estrogen contain GAL.
2. Lactulose also contains GAL.

Galactosemia
Age Nutrient
1
Infants
0 to < 3 mo 3.50 - 3.00 120 (145 - 95) 150 - 125
3 to < 6 mo 3.50 - 3.00 115 (145 - 95) 160 - 130
6 to < 9 mo 3.00 - 2.50 110 (135 - 80) 145 - 125
9 to < 12 mo 3.00 - 2.50 105 (135 - 80) 135 - 120

Girls and Boys
1 to < 4 yr ≥ 30.0 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr ≥ 35.0 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr ≥ 40.0 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr ≥ 50.0 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr ≥ 50.0 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr ≥ 50.0 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr ≥ 55.0 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr ≥ 65.0 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr ≥ 65.0 2,900 (2000 - 3300) 2,000 - 3,300
1
2

TABLE 14-2. Galactose-Restricted Diet: Foods Allowed, Limited and Excluded for Children and Adults With
Galactosemia Where Available, mg of Free GAL are Given in Parentheses after Food. Foods Allowed
Contain < 5 mg GAL/100 g, Foods Limited 5 < 20 mg/100 g, and Foods Excluded ≥ 20 mg/100 g.
FOODS FOODS THAT MAY BE FOODS

ALLOWED LIMITED EXCLUDED
(mg GAL 100/g) (mg GAL/100 g) (mg GAL/100 g)
BEVERAGES
Carbonated drinks Apple juice 14 Buttermilk, coffee
Drinks that do not contain lactose Beer 11 Drinks that contain whole milk, skim milk,
Fruit drinks that do not contain apple, Champagne 12 nonfat dried milk, and/or evaporated or
banana, orange, papaya, pineapple Orange juice 19 condensed milk
and/or pear juices Pear juice 7 Drinks containing calcium caseinate or
Health Source™ Soy Protein Shake sodium caseinate
Isomil ®, Soy Formula With Iron Hot chocolate
(powder) Imitation or filled milks
Non-dairy creamer with approved Kefir, Ovaltine ®, and malted milk
ingredients Milk, untreated of any species
Tea Milk treated with Lactobacillus acidophilus
culture or lactase (Lactaid ®)
Papaya juice
Powdered soft drinks with lactose
Soy milk containing carrageenan
Soy milk made with soy flour
Watermelon juice
Wine 46
24
BREADS AND CEREALS

Breads, crackers, and rolls made with Cornflakes 6 Biscuit, muffin, pancake, and waffle mixes
no milk or milk products containing milk
Most bagels Some dry cereals (read labels carefully for
Italian and French bread milk and/or milk products)
Some cooked and prepared cereals Instant Cream of Wheat ®
(read labels) English muffins containing milk
Contact bakeries in your area for the French toast made with milk
names of milk-free breads. Zwieback containing milk
CHEESE/OTHER MILK PRODUCTS

None All cheeses
Mozzarella cheese > 700
Cream
Curds, whey, whey solids
Lactalbumin, lactoglobulin
Sour cream
Soy cheeses containing calcium caseinate
or sodium caseinate
DESSERTS
Angel food cake Any dessert containing chocolate
Cakes, cookies, & pies made from Any dessert containing a questionable food
allowed ingredients Banana bread
Gelatin Chocolate syrup 23
Ice cream or puddings made with Cocoa
water or soy protein isolate Commercially baked cakes, cookies & pies
formula Custard
Water and fruit ices made from Fig Newtons
allowable fruits Ice cream made with milk
Pie crust made with lard or Packaged cake, pie, or cookie mixes 22
shortening containing milk or milk products
Popsicles ® Persimmon cookies
Pudding mixes without milk Pie crust made with butter or margarine
Sorbets made with allowed fruits Puddings made with milk
Sherbet

EGGS
Egg <5 Omelets, soufflés, and other dishes with
Egg Beaters ® added milk
FATS
Animal fat Butter 30
Bacon Cream
Margarines without milk or soy in any Sour cream
form Whipping cream
Mayonnaise
Nondairy coffee creamers free of milk
products or soy products
Oils, vegetable shortening
FRUITS/JUICES
Avocado 1 Apples 9 Applesauce 44
Cherries 3 Apple juice 14 Apricots 32
Fruit cocktail 3 Apple chips 15 Blackberries ND
Grapefruit, raw or juice 4 Banana 10 Blueberries 34
Grapes, green 3 Dates 11 Boysenberries ND
Mango 4 Kiwi and juice 10 Cranberries ND
Nectarines 4 Melon, watermelon 17 Currants ND
Melon, cantaloupe <5 Orange 5 Figs, dried 4100
Strawberries <5 Orange juice 19 Fruit salad ND
Peaches 6 Fruit salad, tropical ND
Pears 9 Gooseberries ND
Plantains 9 Grapes
Plums, purple 7 American ND
Plums, red 6 European 400
Raisin, Golden, seedless 10-15 Grape juice ND
Raspberries 10 Guava ND
Lemons, limes ND
Melon
Casaba ND
Honeydew 29
Persian ND
Mixed fruit ND
Papaya 31
Persimmon, American 38
Persimmon, Japanese ND
Pineapple 22
Prunes ND
Rhubarb ND
Tangerines ND
Watermelon juice 46
GRAINS/GRAIN PRODUCTS
Barley Wheat 6 All packaged grain or flour mixes
Buckwheat containing milk or milk products or soy
Corn, sweet flour
Corn grits, meal, starch
Hominy
Oats
Pasta (macaroni, noodles, spaghetti)
Rice
Rye

LEGUMES, NUTS, SEEDS

Almonds 3 Beans and franks 5 All beans
Brazil nuts ND Coconut 12 Adzuki beans ND
Cashew nuts ND Black beans 17-82
Hazelnuts 3 Broadbeans ND
Macadamia nuts ND Cranberry beans 65
Peanuts 0 Faba 1,280
Peanut butter 0 Great Northern beans 16-80
Pecans ND Kidney beans 32-153
Soy protein isolate ND King and Mungo beans ND
Walnuts ND Limas, baby 29-175
Navy beans 71-104
Pink beans ND
Pinto beans 28-72
Small white beans 34
Soy beans 44
Yellow beans ND
Cottonseed flour ND
Hazelnuts 500
Lentils 78-116
Miso ND
Natto ND
Peas
Chickpeas (Garbonzas) 41-444
Cowpeas ND
Field peas 32
Black-eyed peas 24-62
Green split peas 199
Pigeon peas 55
Yellow split peas 159-188
Pumpkin seeds ND
Safflower seeds, kernels 100
Sesame flour ND
Sesame seeds ND
Soy sauce, fermented 170
Soya flour ND
Tempeh ND
Tofu ND
MEAT, FISH, POULTRY

Kosher frankfurters Breaded or creamed fish, meat, or poultry
Plain beef, chicken, fish, ham, lamb, Canned fish containing hydrolyzed protein
pork, veal Cold cuts containing nonfat milk solids
Organ meats, including brains, kidney,
liver, pancreas, spleen, and/or
sweetbreads (meat by-products)
SNACK FOODS
Crackers, popcorn, potato chips, & Apple chips 15 All foods containing milk products
pretzels free of milk products Banana bread 23
Graham crackers Fig Newtons ® 22
Plain saltines
Soda crackers

SUGARS/SWEETENERS
Beet and cane sugar Honey 7 Apple butter, apple jelly, caramel candy
Corn syrup Jellies and marmalades Equal ® tablets/other artificial sweeteners
Jellies and marmalades containing containing limited fruits containing added lactose
allowed fruits Jellies and marmalades containing
Jelly beans excluded fruits
Licorice Toffee
Maple syrup, molasses
Nutrasweet ® liquid
Saccharin powder or liquid
Taffy
VEGETABLES/JUICES
Fresh, canned, or frozen: Any vegetable to which Frozen French fries/hash browns
Artichokes 0 lactose is added during containing added lactose
Asparagus 2 processing Pizza sauce, no milk 20
Bamboo shoots 0 Breaded, buttered, or Tomatoes, raw 25
Bean sprouts, green <5 creamed vegetables Tomatoes
Beets 1 Bell peppers 11 Paste 66
Cabbage 4 Broccoli 8 Sauce 77
Cauliflower <5 Brussels sprouts 10 Stewed 40
Celery 3 Carrots 7 V-8 juice 38
Chard, Swiss ND Corn curls ND
Corn, sweet 4 Eggplant 5
Cucumber 4 Instant white potatoes 6
Kale 3 Leeks and onions 6
Lettuce 3 Peas, green 6
Mushrooms, common 0 Pumpkin 12
Mustard greens ND Sauerkraut 16
Olives, green 0 Snap beans 5
Okra ND Sweet potatoes 8
Parsley ND Tomato soup, no milk 18
Peppers, hot 3 Turnip, parsnips 6
Potato, white 1 Yams 11
Radishes <1
Spinach <1
Squash, zucchini 3
INGREDIENTS/MISCELLANEOUS
Caramel coloring Baker's ® cocoa, cocoa Bean-O ®
Gravy made with water powder, semisweet Butterscotch and milk chocolate
Lactate, lactic acid, lactylate chocolate, Carrageenan
Olives Carob powder Dietetic foods containing milk products
Pure monosodium glutamate (MSG) Catsup 6 Drugs, mineral and vitamin preparations
Pure seasonings and spices Lactoalbumin, lactoglobulin containing lactose
Vegetable gums including gum Vegetable gums, including Hydrolyzed protein
Arabic, guar acacia, agar, locust Mocha
Worcestershire sauce bean, tragacanth, or Monosodium glutamate (MSG) extender
xanthan Neocalglucon ® (a calcium supplement)
Peppermint, toffee
Spice blends containing lactose
Because of incomplete analysis on free and bound galactose in foods, this list should be considered
transitional and subject to change.
From references 1, 2, 5, 11-13, 18, 25, 26-36, 39, 45, 47, 49, 52-56, 61, 67-69, 74, 81.
van Calcar S: Free galactose in foods. Unpublished data.
Muscle meat may need to be restricted based on data from reference 79.
ND = No data.

TABLE 14-3. Exchange Lists for Children and Adults With Galactosemia1
Food Measure Protein Energy

(g) (kcal)
Fat varies 0 45
2
Fruits, canned, heavy syrup 1/2 cup 0 80
dried 1/4 cup 0 60
fresh 1/2 cup 0 60
juice 4 fl oz 0 60
Isomil ® Soy Protein Isolate Formula With Iron, Powder 3 100 g 12.6 516
Meat: (Exclude organ meats and products containing milk) 1 oz 7.0 75
Soy milk4 8 fl oz 6.6 79
Starch/Bread varies 3 80
Vegetables 2
cooked 1/2 cup 2 25
raw 1 cup 2 25
1
Modified from Exchange Lists for Weight Maintenance. Chicago: The American Dietetic Association, 1995.
2
See Table 14-2 for Foods Allowed, Limited, and Excluded.
3
Supplies 20 kcal/fl oz when mixed according to label directions.
4
Only if made with soy protein isolate and supplemented with vitamins A, D, B12, calcium and phosphorus. Data for
soy milk from reference 52. Must NOT contain carrageenan.

TABLE 14-4. Galactosemia Clinical Summary Sheet
Date of Birth: __________/__________/__________ Age Diagnosed:

Mo Day Year
Medications: Supplements

1
Length/ Weight Head GAL Urine Galactitol EG1P Ferritin Albumin Hgb Calcium Phosphorus Protein Energy
Height Circum
(mo/d/yr) (cm) (kg) (cm) (mg/dL) (mmol/mol creat-) (mg/dL) (ng/mL) (g/dL) (g/dL) (mg) (mg) (g) (kcal)
Galactosemia 275
1
Indicate if mg/dL or µg/g of hemoglobin, EG1P = erythrocyte GAL-1-phosphate.
REFERENCES
1. Acosta PB: Hidden sources of galactose in the environment. Eur J Pediatr 1995;154 (Suppl 2): 587-592.
2. Aman P: Carbohydrates in raw and germinated seeds from mung bean and chick pea. J Sci Food Agric
1979;30:869-875.
3. Andersson L, Bratt C, Arnoldsson KC, et al: Hydrolysis of galactolipids by human pancreatic lipolytic enzymes and
duodenal contents. J Lipid Res 1995;36:1392-1400.
4. Asp N-G: Human small-intestinal ß-galactosidases. Separation and characterization of three forms of an acid
ß-galactosidase. Biochem J 1971;121:299-308.
5. Aspinall GO, Cottrell IW: Polysaccharide of soybeans. VI. Neutral polysaccharides from cotyledon meal. Can J
Biochem 1971;49:1019-1022.
1996.
7. Berry GT, Nissin I, Lin Z, et al: Endogenous synthesis of galactose in normal men and patients with hereditary
galactosaemia. Lancet 1995;346:1073-1074.
8. Berry GT, Wehrli W, Reynolds R, et al: Elevation of erythrocyte redox potential linked to galactonate biosynthesis.
Metabolism 1998;47:1423-1428.
9. Beutler E: Galactosemia: Screening and diagnosis. Clin Biochem 1991;24:293-300.
10. Bohles H, Wenzel D, Shin YS: Progressive cerebellar and extra-pyramidal motor disturbances in galactosaemic
twins. Eur J Pediatr 1986;145:413-417.
11. Carter HE, Hendry RA, Stanacev NZ: Wheat flour lipids. III. Structure of the mono- and di-galactosylglycerol lipids.
J Lipid Res 1961;2:223-227.
12. Cegla GF, Bell KR: High pressure liquid chromatography for the analysis of soluble carbohydrates in defattened
oilseed flours. J Am Oil Chem Soc 1977;54:150-152.
13. Cerbulis J: Sugars in Caracas cacao beans. Arch Biochem Biophys 1954;49:442-450.
14. Charlwood J, Clayton P, Keir G, et al: Defective galactosylation of serum transferrin in galactosemia. Glycobiol
1998;8:351-357.
15. Cleary MA, Heptinstall LE, Wraith JE, Walter JH: Galactosaemia: Relationship of IQ to biochemical control and
genotype. J Inher Metab Dis 1995;18:151-152
16. Date C, Tanaka H, Yoshikawa K, et al: Determination of sugars in daily foods by high pressure liquid
chromatography and gas liquid chromatography. Osaka City Med J 1982;28:67-83.
17. Donnell GN, Bergren WR, Perry G, Koch R: Galactose 1-phosphate in galactosemia. Pediatrics 1963;31:802-810.
18. Dubois M, Geddes WF, Smith F: The carbohydrates of the gramineae. X. A quantitative study of the carbohydrates
of wheat germ. Cereal Chem 1960;37:557-568.
19. Dunger DB, Holton JB: Disorders of carbohydrate metabolism. In Holton JB (ed): The Inherited Metabolic
Diseases. New York: Churchill Livingstone, 1987.
21. Elsas LJ, Fridovich-Keil J, Leslie ND: Galactosemia: A molecular approach to the enigma. Intl Pediatr
1993;8(1):101-109.
22. Fishler K, Donnell GN, Bergren WR, Koch R: Intellectual and personality development in children with
galactosemia. Pediatrics 1972;50:412-419.
24. Friedman JH, Levy HL, Boustany RM: Late onset of distinct neurologic syndromes in galactosemic siblings.
Neurology 1989;39:741-742.
25. Fry SC: Phenolic components of the primary cell wall. Feruloylated disaccharides of D-galactose and L-arabinose
from spinach polysaccharide. Biochem J 1982;203:493-504.
26. Fujino Y, Sakata S: Glyceroglycolipids in rice grain. Cereal Chem 1973;50:379-382.
27. Gdala J, Buraczewska L: Chemical composition and carbohydrate content of several varieties of faba bean and
pea seeds. J Animal Food Sci 1997;6:123-135.
28. German Galactosemia Parents Group: Galactose Content of Foods.
29. Gropper SS, Gross KC, Olds SJ: The galactose content of selected fruits and vegetable baby foods: Implications
for infants on galactose-restricted diets. J Amer Diet Assoc 1993;93:328.
30. Gropper S, Weese JO, West PA, Gross KC: Free galactose content of fresh fruits and strained fruit and vegetable
baby foods: More foods to consider for the galactose-restricted diet. J Amer Diet Assoc 2000;100:573-575.
31. Gross KC, Acosta PB: Fruits and vegetables are a source of galactose: Implications in planning the diets of
patients with galactosaemia. J Inher Metab Dis 1991;14:253-258.
32. Gross KC, Weese SJ, Johnson JJ, Gropper SS: Soluble galactose content of selected baby food cereals and
juices. J Food Comp Anal 1995;8:319-323.
33. Harju M: Lactobionic acid as a substrate of ß-galactosidases. Milchwissenschaft 1990;45:411-415.

34. Harvey CD, Jenness R, Morris HA: Gas chromatographic quantitation of sugars and nonvolatile water-soluble
organic acids in commercial cheddar cheese. J Dairy Sci 1981;1648-1654.
35. Hettinga DH, Miah AH, Hammond EG, Reinbold GW: Sensitive enzymatic method for determination of glucose
galactose and lactose in cheddar cheese. J Dairy Sci 1970;53:1377-1380.
36. Holton JB: Galactosemia. In Schaub J, et al (eds): Inborn Errors of Metabolism. New York: Raven Press, 1991.
37. Holton JB, Walter JH, Tyfield LA: Galactosemia. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of
Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing Division, 2001, pp 1553-1587.
38. Johnson RN: A study of five calcium supplements: Estimation of calcium absorption and sodium content. Eur J
Clin Nutr 1991;45:117-119.
39. Jurcevic A, Dzamic M, Kapor S, Jankovic J: Sugars and flavour substances of table grape cultivars during cold
storage. Acta Horticulturae 1983;138:147-154.
40. Kaufman FR, Donnell GN, Lobo RA: Ovarian androgen secretion in patients with galactosemia and premature
ovarian failure. Fertil Steril 1988;47:1033-1034.
41. Kaufman FR, Loro ML, Azen C, et al: Effect of hypogonadism and deficient calcium intake on bone density in
patients with galactosemia. J Pediatr 1993;123:365-370.
42. Kaufman FR, Reichart JKV, Ng WG, et al: Correlation of cognitive, neurologic and ovarian outcome with the
Q188R mutation of the galactose-1-phosphate uridyltransferase gene. J Pediatr 1994;125:225-227.
43. Komrower GA: Galactosaemia: Thirty years or the experience of a generation. J Inher Metab Dis
1982;5 (Suppl 2):96-104.
44. Komrower G, Lee D: Long-term follow-up of galactosemia. J Pediatr 1970;102:75-77.
45. Kumar A, Weatherly MR, Beaman DC: Sweeteners, flavorings, and dyes in antibiotic preparations. Pediatrics
1991;89:352-360.
46. Lai K, Langley SD, Singh RH, et al: A prevalent mutation of galactosemia among Black Americans. J Pediatr
1996;128:89-95.
47. Lepage M: The lipid components of white potato tubers (Solanum tuberosum). Lipids 1968;3:477-481.
48. Levy H, Sepe SJ, Shih VE, et al: Sepsis due to Escherichia coli in neonates with galactosemia. N Engl J Med
1972;297:823-825.
49. Lineback DR, Ke CH: Starches and low-molecular-weight carbohydrates from chick pea and horse bean flours.
Cereal Chem 1975;52:334-347.
50. Lo W, Packman S, Nash S, et al: Curious neurologic sequelae in galactosemia. Pediatrics 1984;73:309-312.
51. Manis FR, Cohn LB, McBride-Chang C, et al: A longitudinal study of cognitive functioning in patients with classical
galactosaemia, including a cohort treated with uridine. J Inher Metab Dis 1997;20:549-555.
52. Matthews RH, Pehrsson PR, Farhat-Sabet M: Sugar Content of Selected Foods: Individual and Total Sugars.
Home Economics Research Report No 48. USDA, Washington, DC: US Govt Printing Office, 1987.
53. Minka S, Laurent G, Bruneteau M, et al: Isolation and composition of glycolipids from corn flour. Food Chem
1991;39:329-336.
54. Montgomery R, Smith F: A review of carbohydrate of wheat and other cereal grains. Agric Food Chem 1956;4:716-
720.
55. Mustranta A, Ostman C: Enzymatic determination of lactose and galactose in foods: NMKL collaborative methods
performance study. J AOAC Intl 1997;80:584-590.
56. Naivikul O, D'Appolonia BL: Comparison of legume and wheat flour carbohydrates. I. Sugar analysis. Cereal
Chem 1978;55:913-918.
57. Nelson D: Verbal dyspraxia in children with galactosemia. Eur J Pediatr 1995;154 (Supple 2):56-57.
58. Ng WG, Kaufman FR, Donnell GN: Deficit of uridine diphosphate galactose in galactosaemia. J Inher Metab Dis
1989;12:257-266.
59. Ng WG, Xu YK, Kaufman FR, et al: Biochemical and molecular studies of 132 patients with galactosemia. Hum
Genet 1994;94:359-363.
60. Nicar MJ, Pak CYC: Calcium bioavailability from calcium carbonate and calcium citrate. J Clin Endocrinol Metab
1985;61:391-393.
61. Nickerson TA: Why use lactose and its derivatives in foods? Food Tech 1978;32:40-46.
62. Orestein KS, McGuire EJ, Berry GT, et al: Abnormal galactosylation of complex carbohydrates in cultured
fibroblasts in patients with galactose-1-phosphate uridyltransferase deficiency. Pediatr Res 1992;31:508-511.
63. Palmieri M, Mazur A, Berry GT, et al: Urine and plasma galactitol in patients with galactose-1-phosphate
uridyltransferase deficiency galactosemia. Metabolism 1999;48:1294-1302.
64. Panayotatos N, Villemez CL: The formation of -(1-4)-D-galactan chain catalyzed by a phaseolus aureus enzyme.
Biochem J 1973;133:263-271.
65. Pesce MA, Bodourian SH: Clinical significance of plasma galactose and erythrocyte galactose-1-phosphate
measurements in transferase-deficient galactosemia and in individuals with below normal transferase activity.
Clin Chem 1982;28:301-305.
66. Prestoz LLC, Couto AS, Shin YS, Petry KG: Altered follicle stimulating hormone isoforms in female galactosemia
patients. Eur J Pediatr 1997;156:116-120.

67. Reynolds LM, Henneberry GO, Baker BE: Studies on casein. II. The carbohydrate moiety of casein. J Dairy Sci
1959;42:1463-1471.
68. Ring SG, Selvendran RR: An arabino-galactoxyloglucan from the cell wall of Solanum tuberosum. Phytochemistry
1981;20:2511-2519.
69. Saunders RM: The sugars of safflower. J Am Oil Chem Soc 1970;47:254-255.
70. Segal S: Disorders of galactose metabolism. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of
Inherited Disease, ed 7. New York: McGraw-Hill Information Services Co, 1995, pp 967-1000.
71. Segal S: Galactosaemia today: The enigma and the challenge. J Inher Metab Dis 1998;21:455-471.
72. Shield JPH, Wadsworth EJK, MacDonald A, et al: The relationship between genotype to cognitive outcome in
galactosaemia. Arch Dis Child 2000;83:248-250.
73. Stallings V, Oddleifson NW, Negrini BY, et al: Bone mineral content and dietary calcium intake in children
prescribed a low lactose diet. J Pediatr Gastroent Nutr 1994;18:440-445.
74. Stepak Y, Lifshitz A: Identification and determination of sugars in some fruit juices. J Am Oil Chem Soc
1971;54:1215-1217.
75. Stibler H, von Dobeln V, Kristiansson B, Grithenberg C: Carbohydrate-deficient transferrin in galactosaemia. Acta
Paediatr 1997;86:1377-1378.
76. Waggoner DD, Buist NRM, Donnell GN: Long term prognosis in galactosaemia: Results of a survey of 350 cases.
77. Waisbren SE, Norman TR, Schnell RR, Levy HL: Speech and language deficits in early treated children with
galactosemia. J Pediatr 1983;102:75-77.
1977;30:1269-1280.
79. Weismann N, Rosé-Beutler B, Schlüchter R: Leguminosae in the diet: The raffinose-stachyose question. Eur J
Pediatr 1995;154 (Suppl 2): S93-S96.
80. Wehrli SL, Berry GT, Palmieri M, et al: Urinary galactonate in patients with galactosemia: Quantitation by nuclear
magnetic resonance spectroscopy. Pediatr Res 1997;42:855-861.
81. Wood PJ, Siddiqui IR: Isolation and structural studies of a water-soluble galactan from potato (Solanum
tuberosum) tubers. Carbohydr Res 1972;22:212-220.
82. Yamazaki T, Mino M, Hayashi M: Urinary and serum galactitol in galactosemic patients. Acta Paediatr Jpn
1991;33:61-70.

PROTOCOL 15 — Glucose Transport Protein Defect, Pyruvate Dehydrogenase
Complex Deficiency, and Intractable Seizures

RCF ® Ross Carbohydrate-Free Soy Formula Base With Iron or
ProViMin ® Protein-Vitamin-Mineral Formula Component With Iron Powder
I. Introduction
A. Glucose Transport Protein (GLUT1) Deficiency
D-Glucose is the major fuel for cellular metabolism. Absorption and cellular uptake of glucose
are regulated by a system of tissue-specific glycoproteins that maintain glucose homeostasis in
the body (5, 20, 46).
GLUT1 is a facilitative glucose transport protein found in erythrocytes, fibroblasts, and the
blood-brain barrier. GLUT1 functions effectively in glucose uptake by tissue in the absence of
insulin (20).
DeVivo, et al (17) reported two patients with myoclonic seizures and developmental delay.
These patients presented with depressed cerebrospinal fluid (CSF) glucose concentrations,
normal concentrations of blood glucose, and normal to low CSF lactate, suggesting a defect in
GLUT1 transport. The defect may be due to a nonsense mutation in the GLUT1 gene (61).
Additional children with GLUT1 defect have been described (14). Clinical features include
seizures, delayed mental and motor development, hypotonia, and impaired language skills and
behavior. Onset of symptoms range from 2 to 27 months of age.
Outcome of Nutrition Support of GLUT1 Deficiency
The ketogenic diet has reduced or eliminated seizures within several days of diet onset (14) and
improved psychomotor development. Mild cognitive impairment, speech and motor delay may
persist. Early diagnosis and diet intervention may lessen the pathophysiology associated with the
GLUT1 defect (14).
B. Pyruvate Dehydrogenase (PDH) Complex Deficiency
PDH complex irreversibly converts pyruvate, the end product of glycolysis, into acetyl-CoA
(AcCoA), a major fuel for the Krebs Cycle and substrate for fatty acid synthesis. Pyruvate can also
be carboxylated to oxaloacetate (OAA) via pyruvate carboxylase (PC), transaminated to alanine
(ALA) via aminotransferases or anaerobically converted to lactate by lactate dehydrogenase
(LDH) (Figure N).
PK LDH
Glucose PEP Pyruvate* Lactate*
PC AAT
PEPCK Biotin PDH
Thiamin Alanine*
Aspartate Oxaloacetate AcCoA Fatty

Acids
Site of enzyme malfunction AAT = Alanine aminotransferase
* Accumulates in untreated PDH deficiency PEP = Phosphoenolpyruvate
PEPCK = PEP carboxykinase
PK = Pyruvate kinase
LDH = Lactate dehydrogenase
Figure N. Metabolic fates of pyruvate
284 Glucose Transport Protein Defect, PDH Complex Deficiency, and Intractable Seizures © 2001 Ross Products Division
PDH deficiency, a commonly recognized cause of lactic acidosis (11, 34), inhibits the normal
oxidative metabolism of carbohydrate and prevents production of the majority of ATP. This enzyme
complex contains several functional catalytic proteins; E1α, E1ß, E2, E3, and protein X (56). This
protocol discusses treatment of deficiencies of E1α or E1ß subunits. A defect in a functional
component of the PDH enzyme results in mild to severe lactic acidosis and elevated plasma ALA
and pyruvate concentrations. Age of clinical presentation varies from neonatal to early childhood.
Individuals presenting as neonates suffer severe lactic acidemia and have lower enzyme activity
than individuals presenting in childhood.
Outcome of Nutrition Support of PDH Deficiency
The severity of lactic acidemia is a function of severity of the PDH defect. Patients presenting as
neonates suffer the most severe lactic acidemia and usually die by 6 months of age (7, 34, 56).
Children presenting later in life have greater residual enzyme function and milder phenotype. They
have moderate lactic acidemia, transient acid-base perturbations, and psychomotor retardation. A
percentage of these patients will die before age 3 years. Cerebral atrophy has been reported in
many patients presenting neonatally and in some children with psychomotor retardation (62).
The heterogeneity associated with severe lactic acidemia makes it difficult to predict
outcome. Although patients with higher residual enzyme activity appear to have a less severe
phenotype than patients with less enzyme activity, there is no good correlation between residual
enzyme activity and morbidity and mortality (56).
Use of dichloroacetate (DCA), an inhibitor of PDH kinase that maintains activity of PDH, can
reduce cerebral lactate and CSF concentrations of lactate and pyruvate (67, 70). Use of DCA is
beneficial in eliminating or reducing seizures, infantile spasms, and myoclonic seizures (38, 67).
Efficacy of a ketogenic diet is not well established. Kerr (32) reported reduced concentrations
of blood lactate and "probable" increased life span in two brothers with PDH deficiency. Initiation of
a ketogenic diet at an early age may improve neurologic function and delay death (9, 22, 56, 73).
Thiamin-responsive PDH has been described in several patients (51, 58) with decreased blood
lactate, increased residual enzyme activity in cultured fibroblasts and lymphocytes (51), and
improved facial muscle strength (58).
C. Intractable Seizures
Ketogenic diets high in dietary fat (ie, 87-92% of total energy) are used to control intractable
seizures when other methods of treatment fail. Both long-chain-fats and medium-chain-fats are used
in ketogenic diets with similar success in controlling seizures (19, 25, 31,35, 53, 59, 60). Use of
ketogenic diets in treating seizures was based on early observations that starvation depressed
seizure activity. In 1921, Wilder proposed a high-fat diet to mimic starvation (75). Diet therapy is
most effective for control of myoclonic seizures, infantile spasms, and atonic/akinetic seizures.
Variable success has been found in refractory seizures (54).
The mechanism of antiepileptic action of the ketogenic diet is unknown. Several theories have
been presented, including acid-base disturbances, increased serum lipids, and increased ratio of
adenosine triphosphate (ATP) to adenosine diphosphate (ADP) in the brain (16, 18). Neither an
excitatory nor an inhibitory effect of ketone bodies on neurotransmission has been shown (69).
Outcome of Nutrition Support of Intractable Seizures
Livingston (43) reported complete control of myoclonic seizures in 54% of his patients and
reduction of seizures in another 26% of patients placed on ketogenic diets. Others have reported
similar success showing that approximately 50% of patients with intractable seizures have
improvement or elimination of seizures (26, 35, 53, 59, 72). Adults do not respond to diet as well
as children (53, 54), but the ketogenic diet may be effective in adults with generalized and partial
epilepsy (63). Length of time to clinical response on the ketogenic diet varies from days to weeks
(3, 19, 25, 27, 35, 53, 59). Recommendations for length of time to maintain diet differ, but most
clinicians recommend that diet continue for 2 years. Most patients who respond positively to diet
either remain seizure-free or have continued improvement upon cessation of diet.
Reported complications associated with diet are numerous. These include reduced bone mass,
renal calculi (29), lipemia retinalis, cardiovascular complications (6), pancreatitis, impaired
neutrophil function (77), hypoalbuminemia (2), hypertriacylglycerolemia (68), constipation, anorexia,
dehydration, and refractory vomiting (2). Use of predominantly high-fat food as the mainstay of the
ketogenic diet results in decreased nutrient intake, often requiring carbohydrate-free mineral/vitamin
© 2001 Ross Products Division Glucose Transport Protein Defect, PDH Complex Deficiency, and Intractable Seizures 285
supplements. Compliance to the ketogenic diet may be poor. Success is dependent on a
multidisciplinary approach, constant supervision, and encouragement of families and patients.
II. Establish Diagnosis

A. The Defects
1. GLUT1 transport protein defect.
2. PDH deficiency — of E1α or E1ß subunit.
3. Intractable seizures — unresponsive to standard pharmacologic therapy.
1. Infants and toddlers with any of the following clinical or laboratory signs should be evaluated
for GLUT1 transport protein defect:
a. Seizures, psychomotor retardation, cognitive delays, hypotonia (14, 17), and ataxia.
b. Below-normal CSF glucose with normal blood glucose and normal-to-low CSF lactate.
2. Infants with any of following clinical or laboratory signs should be evaluated for PDH
deficiency (28, 34, 57).
a. Hypotonia or hyporeflexia; failure to thrive; seizures; dysmorphic features including wide
nasal bridge, narrow facial appearance; upturned nostrils; microcephaly; psychomotor
retardation; ataxia; central hypoventilation or recurrent apnea (34).
b. Lactic acidosis; elevated plasma ALA or elevated blood pyruvate concentrations (32, 34).
Lactate:pyruvate ratio is frequently normal, except during acute illness (34).
c. Enzyme activity for PDH deficiency
1) Many enzyme defects cause lactic acidosis (Figure N) (34).
2) Measure enzyme activity in 2 or more of following tissues: cultured skin fibroblasts,
cultured lymphocytes, skeletal muscle, other organs.
3) See reference 34 for methods of diagnosis.
3. Any patient with intractable seizures not responsive to pharmacologic therapy should be
evaluated for ketogenic diet.
III. Rationale for Nutrition Support

1. GLUT1 and intractable seizures:
a. Provide high-fat, very-low-carbohydrate diet as tolerated to reduce or eliminate seizures.
2. PDH deficiency:
a. Ketogenic diet may improve neurologic function and survival in patients with some
residual enzyme activity (55, 56, 73, 74)
b. Restrict carbohydrate, the primary precursor of pyruvic acid.
1. PDH Deficiency
a. Supplement lipoic acid if lipoamide dehydrogenase deficiency is present, but it has not
proven beneficial (34).
b. Supplement thiamin to prolong half-life of any residual PDH (34, 56).
c. Supplement DCA to prolong half-life of PDH (67).
C. Supplement "Conditionally Essential" Nutrients
1. Supplement L-carnitine if hypocarnitinemia is present (13).
IV. Establish Goals of Nutrition Support

A. Growth, Development, and Nutrition Status
adults.
3. Restrict psychomotor deterioration in GLUT1 transport defects.
4. Maintain urine ketones in range that reflects ketosis desired.
5. Maintain normal acid-base balance.
6. Maintain normoglycemia.
7. Maintain fluid status at level sufficient to eliminate or reduce seizures.
8. Maintain normal bowel function.
9. Provide sufficient vitamin D, calcium, and phosphorus to maintain adequate bone mass (29).
B. Plasma Carnitine Concentration
1. Maintain normal concentration of plasma free carnitine ≥ 30 µmol/L (13).
C. PDH Deficiency Only
1. Maintain normal plasma concentrations of ALA, lactate, and pyruvate as determined by
laboratory used.
2. Maintain CSF pyruvate concentrations between 40 and 150 µm (56).
Warning: Plasma pyruvate concentrations are difficult to ascertain. Proper laboratory
methods are essential for interpreting data.
V. Establish Prescription
A. Diet
1. Energy.
a. Prescribe amount that should support normal weight gain in infants and children and
b. For patients with intractable seizures, energy intakes of 75% to 125% of Recommended
Dietary Allowances (RDAs) (24) have been used to maintain ketosis (19, 25, 35, 53, 59,
60).
2. Fat.
a. Prescribe 87% to 92% of energy as fat (ie, 3:1-5:1 ratio of fat:carbohydrate plus protein).
3. Protein.
a. Prescribe between 8% and 13% of energy as protein (Table 15-1, p 288).
Warning: Long-term Inadequate protein intake will result in failure to thrive in infants,
weight loss in children, low plasma transthyretin concentration, osteopenia,
and hair loss. Hypoalbuminemia has been described in patients on ketogenic
diets (2, 10).
4. Carbohydrate.
a. Prescribe carbohydrate to provide remaining energy.
5. L-Carnitine.
a. Prescribe sufficient carnitine to maintain normal plasma free carnitine concentrations.
b. For patients with PDH deficiency, 50-100 mg/kg has been used (33, 71).
Warning: High intakes of L-carnitine may interfere with ketogenesis (53).
6. Thiamin (PDH deficiency only)
a. Prescribe pharmacologic amount.
b. Amounts ranging from 100 to 1800 mg/day have been recommended (7, 9, 21, 51, 55,
74).
7. Fluid
a. Provide amount that will supply water requirements (Table 15-1, p 288). Under normal
circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL fluid to children
and adults for each kcal ingested (4).
b. Some physicians recommend restriction of fluid (800-1200 mL/day) to accelerate ketosis
in children with intractable seizures (25, 27, 35). Others have reported maintenance of
ketosis with adequate fluid intakes (19, 53).
Warning: Over-restriction of fluid may lead to dehydration, constipation, renal calculi,
and acid-base disturbances.
B. Drugs
1. Bicarbonate (PDH deficiency only).
a. Prescribe amount that, with diet and citrate, maintains normal blood pH.
b. Amounts prescribed by various investigators are given below:
1) 10 mmol/kg/day (8).
2) 100 mEq/day (11).
3) 1 mEq/kg/day.
4) 15 mEq every 4 hours (33).
2 DCA (PDH deficiency/lactic acidemia only).
a. Investigational New Drug application required or contact clinicians listed in Table 15-2,
p 288, for referral of patients.
b. Dosage of DCA for treatment of lactic acidosis ranges from 15 mg/kg every 2 days to
150 mg/kg daily (40, 41, 49, 55). Sufficient inhibitory effect of DCA on PDH kinase without
toxic effects has been achieved at a dose of approximately 50 mg/kg/day (34).
c. Plasma DCA concentrations should be routinely monitored to prevent toxicity (40).
3. Antiepileptic medication (if applicable).
a. Modify as needed after initiation and stabilization of ketosis.
b. Many patients with intractable seizures can be weaned from antiepileptic medications
after ketosis is stabilized and patient has shown decreased number of seizures or
complete seizure control.
Warning:
• Many medications contain carbohydrate as inert ingredient (23, 42).
Carbohydrate content of medications change frequently. Contact
manufacturers with each new prescription for accurate, up-to-date information.
• Barbiturates may be contraindicated for patients with GLUT1 deficiency (36).
VI. Fill Prescription

A. Protein
1. Calculate amount of protein provided by RCF, ProViMin, beikost, or table foods (Tables 15-3
and 15-4, pp 289-290) required to fill protein prescription.
a. For more information on nutrient content of beikost (baby foods), contact the following
manufacturers:
1-800-233-2468 1-800-443-7237 Pittsburgh, PA 15219
1-800-872-2229
Note: ProViMin may be used in place of RCF or with RCF in filling the protein
prescription.
B. Fat
1. Calculate amount of fat provided by RCF, ProViMin, beikost, or table foods required to fill
protein prescription.
2. Subtract amount determined above from total fat prescription.
3. Supply remaining fat prescription with vegetable oil (8 kcal/mL) (19, 22, 53, 76).
a. Fractionated coconut oil has been suggested as part of total daily fat prescription for
treatment of intractable seizures to enhance ketogenesis (31, 59, 60) but is expensive and
other vegetable oils are efficacious.
C. Carbohydrate
1. Calculate amount of carbohydrate provided by RCF, ProViMin, beikost, or table foods
required to fill protein and fat prescriptions (Tables 15-3 through 15-4, pp 289-290).
2. Subtract amount determined above from total carbohydrate prescription.
3. Supply any remaining carbohydrate with Polycose ® Glucose Polymers powder (23 kcal/Tbsp,
3.8 kcal/g) (Appendix 9, p A-9), sugar (48 kcal/Tbsp), beikost, or table food (Table 15-3, p 289).
b. All foods and powdered carbohydrate sources must be carefully weighed using a gram
scale.
Warning: Antiepileptic medications may contain carbohydrate which must be
calculated in the diet plan if alternative medications cannot be used.
1. Add prescribed liquid L-carnitine to RCF or ProViMin mixture.
2. If L-carnitine is not added to RCF/ProViMin mixture, administer with each meal.
3. L-carnitine tablets are available.
Warning: Liquid L-carnitine may contain carbohydrate.
E. Thiamin (PDH Deficiency Only).

1. Administer orally with each feed (Table 15-2, p 288).

1. RCF without ProViMin .
a. Add sufficient boiled, cooled water to RCF, fat, and carbohydrate mixture to yield
prescribed volume. Tap water may replace boiled, cooled water when preparing RCF for
b. Shake well until contents are thoroughly mixed.
2. RCF with ProViMin or ProViMin alone.
a. Measure or weigh specified amounts of boiled, cooled water, RCF, ProViMin, fat, and
carbohydrate into clean containers.
b. Pour 1/2 specified amount of boiled, cooled water into clean blender. Running blender at
slow speed, gradually add ProViMin and blend total mixture for approximately 15 seconds.
c. Slowly pour specified amount of RCF, fat, and carbohydrate and additional water to make
prescribed volume into blender and continue blending for 1 to 3 seconds.
before feeding.
6. Notify parents (caretakers) when they may discontinue using aseptic technique in preparing
Warning: All fluid should be carefully measured using a graduated cylinder or other
calibrated instrument.
G. Diet Guide
each diet change.
2. Provide RCF/ProViMin mixture evenly with each feed throughout day.
3. Maintain fat:carbohydrate plus protein ratio evenly with each feed.
4. All foods must be carefully weighed on metric scale accurate to within 1 gram. Failure to
accurately weigh all foods could result in reduction of ketosis and increased seizure activity.
VII. Diet Initiation

A. Intractable Seizures
1. Protocols for diet introduction requiring fasting and hospitalization are available for
establishing ketosis (25, 35, 44).
2. Refer to references 25 and 44 for specific guidelines and protocol regarding hospitalization
and fasting.
3. For patients with PDH deficiency and GLUT1 deficiency, hospitalization and fasting may not
be required.

1. Determine if diet provides nutrients in amounts prescribed in Section V, Establish Prescription,
p 282 .
a. See Table 15-3, p 289, for composition of RCF and ProViMin and Appendix 9, p A-9, for
composition of Polycose.
not available.
b. If RCF or ProViMin mixture provides < 100% of RDIs for infants and < 75% for children
and adults, supplement diet with needed minerals and vitamins if not provided by beikost
or table foods and laboratory tests indicate need (Appendix 11, p A-10, for composition of
supplements).
Warning: Carefully check all mineral and vitamin supplements for carbohydrate
content.
B. Osmolarity
1. If concentration of prescribed RCF or ProViMin mixture is > 27 kcal/fl oz, determine if
osmolarity is in acceptable range.
b. See Appendix 19, p A-21, for osmolarity of RCF and ProViMin.
2. If osmolarity is > 450 mosm/L for neonates (45), > 750 mosm/L for children, > 1,000 mosm/L
for adults (65), or greater than tolerated by patient, increase water content of prescribed
medical food mixture and recalculate its osmolarity.
renal solute load.
recalculate.

A. Acid-Base Status
1. Measure blood pH, gases, electrolytes, lactate, and pyruvate as needed to maintain near
normal acid-base status.
B. Presence of Ketosis
1. Measure urine ketones after first void of morning using Ketostix ® (Bayer Corporation Division,
Elkhart, IN).
a. Ketones may be lowest in morning, which may lead to transient seizure activity (25, 53,
59, 60).
2. Urine ketone concentrations should be medium to large.
3. If urine contains no or low ketones:
a. Increase fat in diet by 5% and decrease carbohydrate by ~ 10%, which will maintain
prescribed energy intakes.
b. Skipping 1 or 2 meals may accelerate ketosis.
4. If urine contains very large amount of ketones:
a. Decrease fat in diet by 5% and increase carbohydrate by ~ 10%, which will maintain
prescribed energy intakes.
b. Excess ketosis can lead to nausea and vomiting.
Warning: Infants may have difficulty maintaining ketosis and normoglycemia.
C. Protein Status
1. Evaluate plasma albumin and transthyretin concentrations every 3 months (Appendix 17,
a. Plasma transthyretin concentration provides a more reliable and rapid indication of protein
b. Plasma albumin concentration may be in the normal range when plasma transthyretin
concentration shows a clear deficiency (1).
a. Increase prescribed protein by 5% to 10% using RCF/ProViMin and reevaluate plasma
albumin or transthyretin concentration in 1 month.
D. Carnitine Status
1. Measure free plasma carnitine concentration every 3 months until patient is 12 months of age
and every 6 months thereafter.
2. If free carnitine concentration is < 30 µmol/L or below normal for laboratory used, increase
amount of carnitine prescribed by 5% to 10%.
E. Iron Status
1) Increase iron intake to 2 mg/kg with supplements (carbohydrate-free ferrous sulfate ).
a. Evaluate hemoglobin and hematocrit concentration at 6, 9, and 12 months of age and
F. Blood Glucose Concentrations
1. Transient hypoglycemia may occur during initial phase of ketogenic diet.
a. Some researchers recommend no treatment unless blood glucose concentrations are
< 40 mg/dL and symptoms occur (25, 53, 60).
1) Symptoms include paleness, sweaty forehead, excess sleep, rapid pulse, dizziness,
and nausea.
2) If symptoms are present, offer 40 mL orange juice (approximately 5 g CH2O) or other
simple carbohydrate (eg, liquid glucose) and recheck blood glucose in 1 hour.
3) If symptoms persist, offer another 40 mL orange juice (approximately 5 g CH2O) or
simple carbohydrate and recheck.
b. During initiation of fasting or diet, monitor blood glucose every 4-6 hours for first 48 to
72 hours and periodically for several days thereafter (19).
Warning: Amount of carbohydrate offered may be greater than 5 g depending on blood
glucose concentration and severity of symptoms.
G. Growth Status
a. Measure monthly to 1 year of age, every 3 months to 4 years, and every 6 months
thereafter. Plot measurements on NCHS growth charts.
b Maintain length/height and weight between 10th and 90th percentiles. Some normal
a. Increase protein and energy prescriptions by 5% to 10% and remeasure in 1 month.
b. If length/height or weight remains low, repeat process until usual growth channel is
achieved.
H. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of protein, fat, and energy weekly or as needed to meet nutrition goals.
not available.
I. Hydration Status
1. Young infants and children cannot verbalize thirst and must be closely monitored.
2. Monitor urine for hydration status.
3. For some patients with intractable seizures, restriction of fluid may be necessary to maintain
urine specific gravity between 1.020 and 1.025 (27).
4. Carefully monitor hydration status during hot summer months.
J. Clinical Summary
A. Example
Establish and fill prescription for 1 year old weighing 9.8 kg using Recommended Daily Nutrient
Intakes from Table 15-1, p 288, and average nutrient contents from Tables 15-3 and 15-4, pp 289
and 290 and Appendix 10, p A-9.
1. Establish prescription for a 3:1 fat:carbohydrate + protein ketogenic diet
Energy 105 kcal/kg x 9.8 kg = 1,029 kcal/day
Protein 1,029 kcal x 0.10 = 103 kcal ÷ 4 kcal/kg = 25.7 g
Fat 1,029 kcal x 0.87 = 895 kcal ÷ 9 kcal/g = 99.5 g
Carbohydrate 1,029 kcal x 0.03 = 31 kcal ÷ 4 kcal/kg = 7.7 g
Fluid 105 mL/kg x 9.8 kg = 1,029 mL/day
2. Fill prescription using RCF:
Food List Measure Protein Fat Carbohydrate Energy
(g) (g) (g) (kcal)
RCF Concentrate 642 mL 25.7 46.2 0.05 520
Soy oil 59 mL 0.0 53.7 0.00 473
Polycose powder 8.2 g 0.0 0.0 7.70 31
Add water to make 1,029 mL (35 fl oz)
Total per day 25.7 99.9 7.75 1024

Divide diet prescription evenly throughout day. Approximate osmolarity of RCF mixture is <
100 mosm/L. Estimated potential renal solute load ≤ 220 mosm.
3. Fill prescription using ProViMin:
Food List Measure Protein Fat Carbohydrate Energy
(g) (g) (g) (kcal)
ProViMin 35 g 25.6 0.5 0.70 109
Soybean oil 112 mL 0.0 101.9 0.00 898
Polycose powder 7.1 g 0.0 0.0 6.70 27
Add water to make 1,029 mL (35 fl oz)
Total per day 25.6 102.4 7.40 1,034

Divide diet prescription evenly throughout day. Approximate osmolarity of ProViMin mixture is
< 110 mosm/L. Estimated potential renal solute load < 230 mosm.
TABLE 15-1. Recommended Daily Nutrient Intakes (Average and Ranges) for Infants and Children with
Seizures 1
Age Nutrient
2
Fat Protein Energy Fluid 3
(% of Energy) (% of Energy) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 87 - 92 8 - 13 120 (145 - 95) 150 - 125
3 to < 6 mo 87 - 92 8 - 13 115 (145 - 95) 160 - 130
6 to < 9 mo 87 - 92 8 - 13 110 (135 - 80) 145 - 125
9 to < 12 mo 87 - 92 8 - 13 105 (135 - 80) 135 - 120
Girls and Boys (kcal/day) (mL/day)

1 to < 4 yr 87 - 92 8 - 13 1,300 ( 900-1800) 900 - 1800
4 to < 7 yr 87 - 92 8 - 13 1,700 (1300-2300) 1,300 - 2,300
7 to < 11 yr 87 - 92 8 - 13 2,400 (1600-3300) 1,600 - 3,300
Women
11 < 15 yr 87 - 92 8 - 13 2,200 (1500-3000) 1,500 - 3,000
15 < 19 yr 87 - 92 8 - 13 2,100 (1500-3000) 1,200 - 3,000
> 19 yr 87 - 92 8 - 13 2,100 (1400-2500) 1,400 - 2,500
Men
11 < 15 yr 87 - 92 8 - 13 2,700 (2000-3700) 2,000 - 3,700
15 < 19 yr 87 - 92 8 - 13 2,800 (2100-3900) 2,100 - 3,900
> 19 yr 87 - 92 8 - 13 2,900 (2000-3300) 2,000 - 3,300
1
Modified from references 35, 53, and 59.
2
87-92% energy as fat calculates to a 3:1 to 5:1 ratio of fat to carbohydrate + protein.
3
older infants and children for each kcal ingested.
TABLE 15-2. Sources of Products to Treat PDH Deficiency
Product Source
Dichloroacetate Peter W. Stacpoole, PhD, MD Richard Haas, MD
Division of Endocrinology and Division of Pediatric Neurology
Metabolism University of California/San Diego
University of Florida Medical Center
College of Medicine 9500 Gilman Drive
Box 100226 La Jolla, CA 92093-0935
Gainesville, FL 32610 (619) 587-4004
(352) 392-2321 FAX (619) 587-8050
Oral Thiamin Nature's Bounty, Inc.

90 Orville Drive
Bohemia, NY 11716
(800) 645-5412
(516) 567-9500
TABLE 15-3. Composition of RCF ® Ross Carbohydrate-Free Soy Formula Base With Iron (Concentrated)
and ProViMin ® Protein-Vitamin-Mineral Formula Component With Iron
Nutrient RCF 1 ProViMin 2

(Per 100 mL) (Per 100 g powder)
Energy, kcal 81 312
Protein, g 4.0 73.0
Carnitine, mg 3.0 40
Taurine, mg 12.0 110
Fat, g 7.2 1.4
Linoleic acid, g 0.81 0
α-Linolenic acid, g 0.04 0
Minerals
Calcium, mg 140 2,400
Chloride, mg/mEq 83/2.34 2,300/65
Iodine, µg 20.3 335
Iron, mg 2.43 40
Magnesium, mg 10.0 200
Phosphorus, mg 100 1,700
Potassium, mg/mEq 146/3.73 3,300/84
Selenium, µg 2.8 63
Sodium, mg/mEq 59.1/2.57 1,200/52
Zinc, mg 1.0 17
Vitamins
A, µg RE 122 2,024
D, µg 2.00 25
E, mg α-TE 2.8 45
K, µg 15 90
Biotin, µg 6.1 100
B6, mg 0.08 1.35
B12, µg 0.61 5.6
Choline, mg 10.5 335
Folate, µg 20 320
Inositol, mg 6.5 105
Niacin, mg/mg NE 1.8/2.8 24.0/40.7
Water, g 89.0 4.0
Other Characteristics
Approx. potential renal solute load mosm 34.8 673
Approx. osmolarity, mosm/L 8.0 200
1
Concentrated.
2
Approximate weights per g powder of ProViMin measured in level, dry US standard household measures:
1 Tbsp = 2.9 g
1/4 cup = 11 g
2/3 cup = 30 g
1 cup = 44 g
TABLE 15-4. Serving Lists for Ketogenic Diets1, 2
Food Group Serving Size Protein Fat Carbohydrate Energy

(approx) (g) (g) (g) (kcal)
Fat 3 varies 0.0 5.0 0.0 45
Grains/Starch 4 1/2 c or 1 slice 3.0 ≤ 1.0 15.0 80
5
Meat, high-fat, and meat substitute 1 oz 7.0 8.0 0.0 100
Milk, high-fat 1 cup 8.0 8.0 12.0 150
Vegetables 1/2 cup, 2.0 0.0 5.0 25
cooked, 1 cup
raw
1
Modified from Exchange Lists for Meal Planning, American Dietetic Association, 1995.
2
These are approximate values. For accuracy, calculate macronutrients and serving sizes for each specific food
offered.
3
Includes avocado, bacon, cream cheese, nuts, olives, and seeds.
4
Includes beans; crackers and snacks; beans and lentils, and starchy vegetables. Serving sizes: 1/2 cup cooked
cereal grain, pasta, or starchy vegetables; 1 slice bread.
5
Includes cheese and peanut butter.
TABLE 15-5. Diet Guide for Ketogenic Diet
Name:________________________________________________ Date: __________/_________/_________
Mo Day Year
Medical Food Mixture Amount Protein Fat CH2O Energy

(g) (g) (g) (kcal)
RCF Concentrate mL
ProViMin g
g/mL
Add water to make fl oz/ mL
Daily Intake Servings Protein Fat CH2O Energy

(g) (g) (g) (kcal)
BREAKFAST
RCF/ProViMin Mixture
Fat
Grains/Starch
Meat, high-fat
Milk, high-fat
Vegetables
MIDMORNING SNACK
LUNCH
Fat
Grains/Starch
Meat, high-fat
Milk, high-fat
Vegetables
MIDAFTERNOON SNACK
DINNER
Fat
Grains/Starch
Meat, high-fat
Milk, high-fat
Vegetables
EVENING SNACK
Volume
(mL)
Daily Totals
Comments
Nutritionist
292 Glucose Transport Protein Defects, PDH Complex Deficiency, and Intractable Seizures
TABLE 15-6. Ketogenic Diet Clinical Summary Sheet

Mo Day Year

Length/ Weight Head Na/K/Cl/ Blood Urine Lactate Pyruvate Plasma Hgb/Hct Albumin/ Ferritin Protein Fat CH2O Energy Fluid
2 1
Height Circum CO glucose Ketones ALA TT
(mg/dL/ (g/dL, (g/day) (g)
(mo/d/yr) (cm) (kg) (cm) (mEq) mmol/L) (mmol/L) (mmol/L) (µmol/L) (g/dL/%) mg/dL) (ng/mL) (g/day) (% energy) (% energy) (kcal) (mL)
1
Transthyretin
REFERENCES
Dis 2000;23 Suppl 1:29A.
2. Ballaban-Gil K, Callahan C, O'Dell C, et al: Complications of the ketogenic diet. Epilepsia 1998;744-748.
3. Barbosa E, Freeman J, Elfert G: Ketogenic diets for treatment of childhood epilepsy. In Walser M, et al (eds)
Nutritional Management. The Johns Hopkins Handbook. Philadelphia: WB Saunders, CO, 1984, pp 272-292.
1996.
5. Bell GI, Burant CF, Takeda J, Gould GW: Structure and function of mammalian facilitative sugar transporters.
J Biol Chem 1993;258:19161-19164.
6. Best TH, Franz DN, Gilbert DL, et al: Cardiac complications in pediatric patients on the ketogenic diet. Neurology
2000;54:2328-2330.
7. Bonne G, Benelli C, DeMeirleir L, et al: E1 pyruvate dehydrogenase deficiency in a child with motor neuropathy.
Pediatr Res 1993;33;284-288.
8. Byrd DJ, Krohn HP, Winkler L, et al: Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic
acidaemia and hyperammonaemia. Eur J Pediatr 1989;148:543-547.
9. Cederbaum SD, Blass JP, Minkoff N, et al: Sensitivity to carbohydrate in a patient with familial intermittent lactic
acidosis and pyruvate dehydrogenase deficiency. Pediatr Res 1976;10:713-720.
10. Couch SC, Schwarzman F, Carroll J, et al: Growth and nutritional outcomes of children treated with the ketogenic
diet. J Amer Diet Assoc 1999;99;1573-1575.
11. Cross JH, Connelly A, Gadian DG: Clinical diversity of pyruvate dehydrogenase deficiency. Pediatr Neurol
1994;10:276-283.
12. DeMeirleir , Lissens W, Denis R, et al: Pyruvate dehydrogenase deficiency: Clinical and biochemical diagnosis.
Pediatr Neurol 1993;9:216-229.
13. DeVivo DC, Bohan TP, Coulter DL, et al: L-Carnitine supplementation in childhood epilepsy: Current perspectives.
Epilepsia 1998;39:1216-1225.
14. DeVivo DC, Burke C, Trifiletti R, et al: Glucose transporter protein deficiency: An emerging syndrome with
therapeutic implications. Am Neurol 1994;36;491.
15. DeVivo DC, Haymond MW, Obert KA, et al: Defective activation of the pyruvate dehydrogenase complex in
subacute necrotizing encephalomyelopathy (Leigh disease). Ann Neurol 1979;6:483-494.
16. DeVivo DC, Leckie MP, Ferrendelli JS, McDougal DB: Chronic ketosis and cerebral metabolism. Ann Neurol
1978;3:331-337
17. DeVivo DC, Trifiletti R, Jacobson RI, et al: Defective glucose transport across the blood-brain barrier as a cause of
persistent hypoglycorrhachia, seizures and developmental delay. N Engl J Med 1991;325:703-709.
18. Dodson WE, Prensky AL, DeVivo DC, et al: Management of seizure disorders: Selected aspects. Part II. J Pediatr
1976;89:695-703.
19. Edelstein SI, Chisholm M: Management of intractable childhood seizures using the non-MCT oil ketogenic diet in
20 patients. J Amer Diet Assoc 1996:96:1181-1182.
20. Elsas LJ, Longo N: Glucose transporters: Human disorders and insulin receptor regulation. Intl Pediatr
1995;10(1):57-68.
21. Endo H, Hasegawa K, Narisawa K, et al: Defective gene in lactic acidosis: Abnormal pyruvate dehydrogenase E1
α-subunit caused by a frame shift. Am J Hum Genet 1989;44:358-364.
22. Falk RE, Cederbaum SD, Blass JP, et al: Ketonic diet in the management of pyruvate dehydrogenase deficiency.
Pediatrics 1976;58:713-721.
23. Feldstein TJ: Carbohydrate and alcohol content of 200 oral liquid medications for use in patients receiving
ketogenic diets. Pediatrics 1996;97:506-511.
25. Freeman JM, Freeman JB, Kelly MT: The Ketogenic Diet: Treatment for Epilepsy, ed 3. New York: Demos
Publications, 2000.
26. Freeman JM, Vinning EPG, Pillar DJ, et al: The efficacy of the ketogenic diet in 1998; A prospective evaluation of
intervention in 150 children. Pediatrics 1998;102:1358-1363.
27. Gasch AT: Use of the traditional ketogenic diet for treatment of intractable seizure epilepsy. J Amer Diet Assoc
1990;90:1433-1434.
28. Harada M, Tanouchi M, Arai K, et al: Therapeutic efficacy of a case of pyruvate dehydrogenase complex deficiency
monitored by localized proton magnetic resonance spectroscopy. Magn Res Imaging 1996;14:129-133.
29. Herzberg GZ, Fivush BA, Kinsman SL, Gearhart JP: Urolithiasis associated with the ketogenic diet. J Pediatr
1990;117:743-745.
30. Hommes FA, Berger R, Luit-DeHaan G: The effect of thiamine treatment on the activity of pyruvate
dehydrogenase: Relation to the treatment of Leigh's encephalomyelopathy. Pediatr Res 1973;7:616-619.
31. Huttenlocher PR, Wilbourn AJ, Signore JM: Medium-chain-triglycerides as a therapy for intractable childhood
epilepsy. Neurology 1971;21:1097-1103.
32. Kerr DS: Treatment of congenital lactic acidosis: A review. Intl Pediatr 1995;10:75-81.
33. Kerr DS, Lap H, Berlin CM, et al: Systemic deficiency of the first component of the pyruvate dehydrogenase
complex. Pediatr Res 1987;22:312-318.
34. Kerr DS, Wexler ID, Zinn AB: Disorders of pyruvate metabolism and tricarboxylic acid cycle. In Fernandes J, et al
(eds): Inborn Metabolic Diseases: Diagnosis and Treatment, ed 3. New York: Springer-Verlag, 2000, pp 126-138.
35. Kinsman SL, Vining EPG, Quaskey SA, et al: Efficacy of the ketogenic diet for intractable seizure disorders:
Review of 58 cases. Epilepsia 1992;33:1132-1136.
36. Klepper J, Fischberg J, Vera JC, et al: GLUT1-deficiency: Barbiturates potentiate haploinsufficiency in vitro.
Pediatr Res 1999;46:677-683.
37. Klip A, Tsakiridis T, Marette A, Ortiz PA: Regulation of expression of glucose transporters by glucose: A review of
studies in vivo and in cell cultured. FASEB J 1994;8:43-53.
38. Kodama S, Yagi R, Ninomiya M, et al: The effect of a high fat diet on pyruvate decarboxylase deficiency without
central nervous system involvement. Brain Dev 1983;5:381-389.
39. Kretzschmar HA, DeArmond SJ, Koch TK, et al: Pyruvate dehydrogenase complex deficiency as a cause of
subacute necrotizing encephalopathy (Leigh disease). Pediatrics 1987;79:370-373.
40. Kuroda Y, Ito M, Toshima K, et al: Treatment of chronic congenital lactic acidosis by oral administration of
dichloroacetate. J Inher Metab Dis 1986;9:244-252.
41. Kuroda Y, Naito E, Takeda E, et al: Congenital lactic acidosis. Enzyme 1987;38:108-114.
42. Kumar A, Aitas AT, Hunter AG, Beaman DC: Sweeteners, dyes and other excipients in vitamin and mineral
preparations. Clin Pediatr 1996;Sept:443-450.
43. Livingston S, Pauli LL, Pruce I: Ketogenic diet in the treatment of childhood epilepsy. Dev Med Child Neurol
1977;19:833-834.
44. MacCracken KA, Scalisi JC: Development and evaluation of a ketogenic diet program. J Amer Diet Assoc
1999;99:1554-1558.
1982.
46. Maher F, Vannucci SJ, Simpson IA: Glucose transport proteins in brain. FASEB J 1994;8:1003-1011.
1987;1:1-17.
48. Matalon R, Stumpf DA, Michals K, et al: Lipoamide dehydrogenase deficiency with primary lactic acidosis:
Favorable response to treatment with lipoic acid. J Pediatr 1984;104:65-69.
49. McCormick K, Viscardi RM, Robinson B, Heininger J: Partial pyruvate decarboxylase deficiency with profound
lactic acidosis and hyperammonemia: Responses to dichloracetate and benzoate. Am J Med Genet
1985;22:291-299.
50. Meites S (ed): Pediatric Clinical Chemistry: Reference Normal Values, ed 3. Washington, DC: AACC Press, 1989.
51. Naito E, Ito M, Takeda E, et al: Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-
responsive congenital lactic acidemia. Pediatr Res 1994;36:340-346.
52. Nordli DR, DeVivo DC: The ketogenic revisited: Back to the future. Epilepsia 1997;38:743-749.
53. Nordli DR, Koenigsberger D, Schroeder J, DeVivo DC: Ketogenic diets. In Resor SR, et al (eds): The Medical
Treatment of Epilepsy. New York: Marcel Dekker, Inc. 1992, p 455-472.
54. Prasad AN, Stafstrom CR, Holmes GL: Alternative epilepsy therapies: The ketogenic diet, immunoglobulins, and
steroids. Epilepsia 1996;37 (Suppl 1):531-593.
55. Przyrembel H: Therapy of mitochondrial disorders. J Inher Metab Dis 1987;10:129-146.
56. Robinson BH: Lactic acidemia: Disorders of pyruvate carboxylase, pyruvate dehydrogenase. In Scriver CR, et al
(eds): The Metabolic and Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing
Division, 2001, pp 2275-2296.
57. Robinson BH, MacMillan H, Petrova-Benedict R, Sherwood WG: Variable clinical presentation in patients with
defective E1 component of pyruvate dehydrogenase complex. J Pediatr 1987;111:525-533.
58. Scholte HR, Busch HFM, Luyt-Houwen IEM: Vitamin responsive pyruvate dehydrogenase deficiency in a young girl
with external ophthalmoplegia, myopathy and lactic acidosis. J Inher Metab Dis 1992;15:331-334.
59. Schwartz RM, Boyes S, Aynsley-Green A: Metabolic effects of three ketogenic diets in the treatment of severe
epilepsy. Dev Med Child Neurol 1989;31:152-160.
60. Schwartz RH, Eaton J, Bower BD, Aynsley-Green A: Ketogenic diets in the treatment of epilepsy: Short-term
clinical effects. Dev Med Child Neurol 1989;31:145-151.
61. Seidner G, Alvarez MG, Yeh JI, et al: GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain
hexose carrier. Nat Genet 1998;18:188-191.
62. Shevell MI, Matthews PM, Scriver CR: Cerebral dysgenesis and lactic acidemia: An MRI/MRS phenotype
associated with pyruvate dehydrogenase deficiency. Pediatr Neurol 1994;11:224-229.
63. Sirven J, Whedon B, Caplan D, et al: The ketogenic diet for intractable epilepsy in adults: Preliminary results.
Epilepsia 1999;40:1721-1726.
1976.
1983;7:280-288.
1989;143:828-832.
67. Stacpoole PW, Barnes CL, Harbanis MD, et al: Treatment of congenital lactic acidosis with dichloroacetate: A
review. Arch Pediatr Adolesc Med 1997;77:535-541.
68. Theda C, Woody RC, Sakkubai N, et al: Increased very long-chain-fatty acids in patients on a ketogenic diet: A
cause of diagnostic confusion. J Pediatr 1993;122:724-726.
69. Thio LL, Wong M, Yameda KA: Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic
transmission. Neurology 2000;54:325-331.
70. Toth PP, El-Shanti H, Eivins S, et al: Transient improvement of congenital lactic acidosis in a male infant with
pyruvate decarboxylase deficiency treated with dichloroacetate. J Pediatr 1993;123:427-430.
71. Uziel G, Garavaglia B, DiDonato S: Carnitine stimulation of pyruvate dehydrogenase complex (PDHC) in isolated
human skeletal muscle mitochondria. Muscle Nerve 1988;11:720-724.
72. Vinning EP, Freemen JM, Ballaban, GK, et al: A multicenter study of the efficacy of the ketogenic diet. Arch Neurol
1998;5:1433-1437.
73. Wexler I, Hemalatha S, McConnell J, et al: Outcomes of pyruvate dehydrogenase deficiency treated with ketogenic
diets: Studies in patients with identical mutations. Neurology 1997;49:1655-1661.
74. Wick H, Schweizer K, Baumgartner R: Thiamine dependency in a patient with congenital lactic acidaemia due to
pyruvate dehydrogenase deficiency. Agents and Actions 1977;7:405-410.
75. Wilder RM: Effects of ketonuria on the course of epilepsy. Mayo Clin Bulletin 1921;2:307-314.
76. Woody RC, Brodie M, Hampton DK, Fiser RH: Corn oil ketogenic diet for children with intractable seizures. J Child
Neurol 1988;3:21-24.
77. Woody RC, Steele RW, Knapple WL, Pilkington NS: Impaired neutrophil function in children with seizures treated
with the ketogenic diet. J Pediatr 1989;115:427-430.
PROTOCOL 16 — Glycogen Storage Disease Types Ia and Ib

RCF ® Ross Carbohydrate-Free Soy Formula Base With Iron or
ProViMin ® Protein-Vitamin-Mineral Formula Component With Iron Powder
I. Introduction
Glycogen storage disease (GSD) type Ia (von Gierke's disease) results from a deficiency of glucose-6-
phosphatase, normally found in liver, kidney, and intestinal mucosa. GSD type Ib results from a defect
in the enzyme glucose-6-phosphate translocase, affecting transfer of glucose-6-phosphate into
endoplasmic reticulum (12). These diseases usually manifest during the first year of life as severe
hypoglycemia or profound hepatomegaly. Secondary biochemical features include
hypertriacylglycerolemia, hypercholesterolemia, hyperuricemia, and lactic acidemia. Platelet
dysfunction, inflammatory bowel disease, and severe neutropenia (type Ib only) have been described
(12). Other forms of GSD type I (ie, Ic and Id) have been reported. However, the subcategories may
not be distinct clinical disorders from GSD type Ib (39, 40).
Glycogen
Glucose-1-P
Glucokinase
ADP ATP
Glucose-6-P* Glucose
H2O Pi
Fructose 6-P Glucose-6-phosphatase Endoplasmic reticulum
Adenine
Fructose 1,6-P Phosphate Trap
Inosine
Lactate* Pyruvate Alanine*

Uric acid*
Fatty acids
Triacylglycerols*
* Accumulates in untreated GSD Type I
TCA
Acetyl-CoA Site of enzyme defect
cycle
Cholesterol* Site of transport defect
Figure O. Hepatic glycogen metabolism in GSD I

In the past, many patients with GSD type I died from complications associated with biochemical
abnormalities. Patients who survived had a poor prognosis. Muscle wasting and stunted growth were
common in poorly controlled individuals. Current diet regimens, resulting in normal blood glucose
concentration, have proven beneficial in eliminating pathophysiologic sequelae found in poorly
controlled patients. Well-controlled patients attain normal linear growth and have dramatically reduced
risk for hepatic adenomas, renal insufficiency, gout, pancreatitis, osteoporosis, and atherosclerosis
(23, 32, 37). Despite good metabolic control, renal insufficiency and hyperlipidemia may still occur.

A. The Defect
1. GSD type Ia results from deficiency of glucose-6-phosphatase, which is normally found in
liver, kidney, and intestine.
© 2001 Ross Products Division Glycogen Storage Disease 301

2. GSD type Ib results from defect in glucose-6-phosphate translocase, affecting transfer of
glucose-6-phosphate into endoplasmic reticulum.
3. GSD type Ic results from defect in microsomal phosphate or pyrophosphate transport.
4. GSD type Id results from defect in microsomal glucose transport caused by deficiency of
GLUT7 transport protein.
1. Infants or children with any of following clinical symptoms and biochemical findings should be
evaluated for GSD type I (7, 12):
a. Hepatomegaly.
b. Growth retardation.
c. Bleeding tendency (1).
d. Severe neutropenia (type Ib) (15, 41).
e. Hypoglycemia.
f. Hyperlacticacidemia.
g. Hyperuricemia (22).
h. Hypertriacylglycerolemia.
i. Hypercholesterolemia.
C. Differential Diagnosis (7, 12)
1. Definitive diagnosis requires liver biopsy and DNA analysis to identify deficiency of glucose-6-
phosphatase or deficiency in any 1 of 3 microsomal translocase systems.
2. Cultured skin fibroblasts or blood CANNOT be used for enzyme diagnosis because glucose-6-
phosphatase is not present in these cell types.

1. Maintain normal blood glucose concentration by providing frequent complex dietary
carbohydrate (CH2O).
2. Maintain normal blood glucose concentration throughout day and night to ameliorate
secondary biochemical abnormalities.

A. Plasma Glucose Concentration
1. Maintain normal plasma glucose concentration between 70 and 120 mg/dL (3.9 and
6.7 mmol/L 2 hrs postprandial) or within normal range found in laboratory used (26, 36).

1. Support normal growth rate of infants and children.
2. Maintain normal development.
a. Avoid prolonged fasting > 5 to 7 hours. Some patients cannot tolerate fasting > 3.5 hours.
b. Avoid excessive hepatic lipid accumulation.
C. Biochemistries
1. Maintain normal plasma biochemistries in ranges noted below or per laboratory used.
Analyte Normal Range
Cholesterol (plasma) < 201 mg/dL (5.20 mmol/L)
1
Lactate Arterial 3.3 - 6.8 mg/dL (0.36 - 0.75 mmol/L)
Venous 4.5 - 11.8 mg/dL (0.50 - 1.30 mmol/L)
Triacylglycerols (plasma) 300 - 700 mg/dL2 (3.4 - 7.9 mmol/L) (treatment range)
Uric acid (serum/plasma) 2.0 - 5.4 mg/dL (119 - 327 mmol/L)
1
Slightly higher lactate concentrations may be acceptable for treatment (12).
2
Patients with GSD type I usually do not attain normal plasma triacylglycerol concentrations and maintain
concentrations of 300 to 700 mg/dL (28).
302 Glycogen Storage Disease © 2001 Ross Products Division

A. Sucrose/Fructose and Lactose/Galactose
1. Limit foods and medications containing sucrose, fructose, lactose, and galactose.
a. Fructose and galactose are metabolized to glucose-6-phosphate and can elevate blood
lactate and triacylglycerol concentrations (9, 29).
b The amount of fructose allowed in the GSD diet is not well described. Very small amounts
may be tolerated by some patients.
Warning: Opinion varies as to extent galactose and fructose should be eliminated from
diet, and age when relaxation in restriction should occur. Dietary lactose
should be limited to ~23 g per day (based on 0.5 L 2% milk) (12).
B. Energy
1. Recommended Dietary Allowances (RDAs) are same as for normal infants and children (14).
2. Intakes should be sufficient to support normal weight gain in infants and children and maintain
normal weight for height in adults (Table 16-1, p 305).
3. Energy intake should be divided into daytime feedings (65% -75% total prescribed energy)
and nocturnal CH2O infusion (25%-35% total prescribed energy).
Warning: Excessive energy intakes may cause obesity and hypertriacylglycerolemia in
individuals with GSD type I (6).
C. Protein
1. Prescribe amount that supplies 10% to 15% of daily energy prescribed (Table 16-1, p 305).
a. Additional protein is not recommended for GSD type I.
D. Fat
1. Prescribe amount that provides 25% to 35% of daily energy requirement (Table 16-1, p 305).
Fat intake may need to be reduced below 25% of energy to prevent obesity in severely
affected patients who require dietary oligosaccharides that lead to energy excess.
a. Prescribe minimum of 3% of total energy as linoleic acid.
b. Prescribe minimum of 1% of total energy as α-linolenic acid.
E. Carbohydrate
1. Recommended amounts will vary based on age, weight, and maintenance of normoglycemia.
a. Prescribe amount that provides remainder of prescribed energy (Table 16-1, p 305).
b. Prescribe as complex CH2O. After 6-8 months of age, supply raw cornstarch at 1.25 to
2.5 g/kg body weight/feeding between meals (8, 16, 30, 31). Actual requirement may be
above or below this range to maintain desired blood glucose concentrations.
1) Cornstarch should be calculated as part of prescribed CH2O energy.
2) Raw cornstarch is not recommended for use in intragastric infusions because of
solidification and clogging of tube.
Warning: Young infants (< 6 months) consuming large amounts of raw cornstarch may
develop gastrointestinaI distress (flatulence, colicky symptoms, diarrhea)
because pancreatic amylase has not reached normal adult activity (21).
F. Fluid
circumstances, offer minimum of 1.5 mL fluid to neonates for each kcal ingested and 1.0 mL
to children and adults (4).
G. Nocturnal Feedings
1. Nocturnal feedings usually provide between 25% and 35% of total daily energy requirements
(30, 44).

2. Intragastric infusion method: Calculation of glucose requirements
a. Glucose requirements vary depending on individual glucose production rates (GPR).
1) The following are normal GPR for different ages (5).
Neonates 5.61 - 6.53 mg/kg/min
Infants < 6 yrs 6.86 - 7.34 mg/kg/min
Late Childhood 5.12 - 5.68 mg/kg/min
2) Reported glucose supplements used to maintain normoglycemia are as follow:
Infants 7 - 9 mg/kg/min (11)
Children < 6 yrs 5 - 7 mg/kg/min (11, 44)
6 yrs ≤ 14 yrs 5 - 6 mg/kg/min (5)
Adolescents 4 - 5 mg/kg/min (11)
Adults 3 - 4 mg/kg/min (12)

A. Protein
1. Calculate amount of RCF, ProViMin (Table 16-3, p 308), beikost, or table foods (Table 16-4,
p 308) required to fill protein prescription. Nutrient information for beikost (baby food) may be
obtained by contacting the following manufacturers:
1-800-233-2468 1-800-443-7237 Pittsburgh, PA 15219
1-800-872-2229
2. Request list of ingredients and nutrient composition.
B. Fat
1. Calculate amount of fat from RCF, ProViMin (Table 16-3, p 308), beikost, or table foods
(Table 16-4, p 308) required to fill fat prescription
2. Subtract amount determined above from total fat prescription.
Note: When using RCF, fat is calculated before protein because of possible excess
fat. If ProViMin is used as sole protein source, protein is calculated first since
ProViMin contains only trace amounts of fat (Table 16-3, p 308).
3. Supply remaining fat prescription (Table 16-1, p 305) with measured amount of oils
(Appendix 10, p A-9), beikost, or table foods (Table 16-4, p 308).
4. Supply 3% of total energy as linoleic acid and 1.0% as α-linolenic acid.
Warning: Essential fatty acid deficiency may occur if intakes of linoleic and α-linolenic
acids are inadequate.
C. Carbohydrate
1. Daytime feedings.
a. Sucrose/Fructose and Lactose/Galactose
1) See Table 16-2, p 306, for foods allowed and restricted in GSD Type I diet.
b. For infants and some toddlers, Polycose (Appendix 9, p A-9) or complex CH2O may be
used to fill prescription (Table 16-1, p 305). Polycose may be added to RCF or ProViMin
mixture.
c. Raw cornstarch (Table 16-5, p 308) replaces complex CH2O when pancreatic amylase
activity is present (beginning with very small amounts of raw cornstarch about mid-
infancy).
1) Infants < 12 months of age have tolerated cornstarch (38) but use of pancreatic
enzyme may be needed. Introduction of very small amounts of raw cornstarch
beginning at 6 months of age may be necessary to induce pancreatic amylase.
Warning: Introduction of excess raw cornstarch may cause diarrhea and flatulence.
d. Recommended complex CH2O supplementation, which makes up part of total CH2O
prescription (Table 16-1 p 305), varies from 1.25 to 2.5 g CH2O/kg/feed.
1) Actual requirements vary. Individualize amount of CH2O to maintain normoglycemia
and promote protein synthesis.

Warning: Inadequate CH2O administration may result in reduced whole body protein
synthesis and elevated plasma lactate concentrations (12, 30, 45).
e. Timing of daytime feeds varies depending on type of CH2O used and patient's ability to
maintain normoglycemia.
1) Spacing of CH2O daytime feeds is usually every 2 to 3 hours for infants and every
3 to 4 hours for children.
2) Doses of raw cornstarch > 2.5 g/kg have maintained normoglycemia longer than 4
hours in some individuals (8, 12).
3) In contrast, feeds < 1.25 g/kg raw cornstarch given more frequently may be beneficial
for some children (43).
f. Administration of RCF or ProViMin/CH2O mixture for infants and children
1) Mix prescribed amounts of Polycose and/or uncooked cornstarch in RCF or ProViMin.
i. Polycose and RCF or ProViMin may be mixed and stored for up to 48 hours.
ii. Add prescribed amount of uncooked cornstarch to RCF or ProViMin at time of
feeding.
2) Uncooked cornstarch may also be given in water and administered in 1:2 ratio.
i. Sugar-free flavoring may be added to water/CH2O mixture to improve
"acceptability."
ii. Administer above mixture between meals at frequencies throughout day that
maintain normoglycemia.
Warning: Exceeding the 1:2 ratio of cornstarch to water will reduce its effectiveness in
maintaining normoglycemia. Cooked cornstarch is not effective in
maintaining normoglycemia.
3) Alternate complex carbohydrates (ie, cooked rice, pasta, rolled oats, millet, couscous,
legumes and lentils) may substitute for raw cornstarch during daytime feeds (12) if
they are effective in maintaining normoglycemia.

1. RCF without ProViMin
a. Add sufficient boiled, cooled water to RCF and carbohydrate mixture to yield prescribed
volume. Tap water may replace boiled, cooled water when preparing RCF for older
infants, children, and adults.
b. Shake well until contents are thoroughly mixed.
2. RCF with ProViMin or ProViMin alone.
a. Measure or weigh specified amounts of boiled, cooled water, RCF, ProViMin, fat, and
carbohydrate into clean containers.
b. Pour 1/2 specified amount of boiled, cooled water into clean blender. Running blender at
slow speed, gradually add ProViMin and blend total mixture for approximately 15 seconds.
c. Slowly pour specified amount of RCF, fat, carbohydrate and additional water to make
prescribed volume into blender and continue blending for 1 to 3 seconds.
4. Warm or cool RCF/ProViMin mixture to room temperature before feeding to infants. Shake
well before feeding.
5. Do not warm RCF/ProViMin mixture in microwave oven. Unevenly heated formula can burn
6. Notify parents (caretakers) when they may discontinue using aseptic technique in preparing
E. Nocturnal Feeding.
1. Several methods may be used to provide CH2O for night feedings.
a. Intermittent oral feedings of raw cornstarch mixed with water (8, 12); Polycose, or raw
cornstarch mixed with RCF or ProViMin.
b. Continuous CH2O source (eg, Polycose ® Glucose Polymers) via intragastric infusion (8,
16, 17, 21, 35).
1) Intermittent oral feeding of raw cornstarch and continuous CH2O infusion have
resulted in similar positive clinical outcomes (6, 30, 44).

2. Calculate amount of Polycose or raw cornstarch (oral feedings only) required to fill patient's
glucose requirement.
3. Polycose may be added to RCF/ProViMin to provide prescribed CH2O (Table 16-1, p 305) and
fed orally or by intragastric infusion.
4. For intragastric infusion, provide sufficient amount of prescribed CH2O mixture to meet
volume required over total hours to prevent premature cessation of CH2O source.
5. Intragastric Infusion Rates.
a. Infusion rates will differ with each patient. Adjust rate to supply prescribed amount of
CH2O over selected period of infusion.
b. To prevent severe hypoglycemia, nocturnal intragastric infusion usually extends for 8 to
10 hours beginning within 3 hours of last daytime feeding and ending 30 minutes after 1st
meal of following morning or within 30 minutes of removal of tube feeding.
Warning: Severe hypoglycemia may occur if oral feeding is not established soon after
infusion is completed.
F. Diet Guide
1. Provide parents, caregivers, or patient with completed Diet Guide (Table 16-6, p 309) with
each diet change.

a. See Protocol 15, Table 15-3, p 289, and Table 16-3, p 308, for composition of RCF and
ProViMin. Nutrient composition of beikost and table foods are dependent on specific foods
prescribed. Contact manufacturer or nutrient database in Amino Acid Analyzer © software
for composition.
not available.
b. If RCF or ProViMin mixture provides < 100% of RDIs for age, supplement diet with
needed minerals and vitamins if not provided by beikost or table foods and laboratory
tests indicate need.
Warning: Low calcium intake (23) and chronic lactic acidosis (27) may result in poor
bone mineralization in patients with GSD type I.
B. Osmolarity
b. Osmolarity of RCF is 0.08 mosm/mL concentrated.
2. If osmolarity is > 450 mosm/L for infants (24), > 750 mosm/L for children, < 1,000 mosm/L for
adults (34), or is greater than tolerated by patient, increase water content of prescribed
1. Dehydration will result if renal solute load is greater than renal-concentrating ability of
patient (13).
renal solute load.
capacity as low as 600 mosm/L .
b. Upper limit of renal solute load for neonates is approximately 1,100 mosm/L (13, 33).
4. If potential renal solute load is excessive, increase water content of RCF/ProViMin mixture
and recalculate.

Warning: Compromised renal failure, found in some patients with GSD type I, may
result in inadequate handling of renal solute load.

A. Blood Glucose Concentration
1. Evaluate blood glucose concentrations (local laboratory measurements) as needed to
maintain between 70 and 120 mg/dL (3.9 to 6.7 mmol/L).
2. Home monitoring.
a. Monitor blood glucose concentrations daily in all children receiving nocturnal infusions or
after diet changes using glucometer.
b. Quantite blood glucose concentration early in morning soon after nocturnal infusion is
completed.
c. Monitor blood glucose concentration of all children until at least 5 years of age. Most
common periods of hypoglycemia are midmorning and midafternoon.
3. If blood glucose concentration is below recommended range:
a. Increase prescribed CH2O by approximately 10% to 15% and decrease fat by an equal
number of kcalories and reevaluate after next feeding or following day at same time of
day.
b. If blood glucose concentration remains low, repeat above process until concentration is in
normal range.
B. Protein Status
1. Evaluate plasma albumin concentration every 3 months during infancy and twice yearly in
children (Appendix 17, p A-18, for standards).
a. Increase prescribed protein by 5% to 10% and reevaluate plasma albumin concentration
in 1 month.
b. If plasma albumin or transthyretin concentration remains low, repeat above process until
C. Iron Status
1. Plasma ferritin concentration:
a. Evaluate at 6, 9, and 12 months of age and yearly thereafter (Appendix 17, p A-18, for
standards).
a. Evaluate hemoglobin, hematocrit and differential at 6, 9, and 12 months of age and every
6 months thereafter (Appendix 17, p A-18, for standards).
D. Plasma Triacylglycerol, Cholesterol, Lactic Acid, and Uric Acid Concentrations
1. Evaluate every 3 months until 3 years of age and every 6 months or as indicated thereafter.
2. Above analytes should be measured along with blood glucose concentration.
3. If plasma triacylglycerol, lactic acid, and uric acid concentrations are above treatment range:
a. Obtain a blood glucose concentration;
1) If low, either increase prescription of cornstarch or other CH2O or adjust schedule of
feeding to provide sufficient CH2O to prevent hypoglycemia.
b. Elevated concentrations of these analytes are negatively related to blood glucose
concentration and indicate poor metabolic control.

E. Growth Status
a. Measure monthly until patient is 1 year old, every 3 months to 4 years of age, and every
6 months thereafter, or as needed. Plot measurements for infants and children on NCHS
growth charts.
b. Maintain length/height and weight between 10th and 90th percentile. Some normal
c. If length/height or weight falls below usual growth channel:
1) Reassess degree of metabolic control (Section IX, Suggested Evaluation of Nutrition
Support, p 302) for blood glucose concentration, and related analytes listed in IX.D,
above.
2) Adjust nutrition support to normalize blood glucose concentration and related analytes
and repeat anthropometrics in 1 month.
3) If length/height or weight remains low, readjust nutrition support until usual growth
channel and/or catch-up growth is achieved.
Warning: Failure to grow is often indicative of poor metabolic control. In GSD type Ib ,
neutropenia resulting in recurrent infections may inhibit growth (38). Some
patients may not achieve growth potential even with good diet compliance
(10).
2. Obesity may be chronic in children with GSD type I who are consuming excessive raw
cornstarch and energy.
a. If weight gain is excessive or above usual growth channel:
1) Calculate total energy intake per day including raw cornstarch regimen to determine if
energy intake is excessive.
2) Adjust energy prescription to maintain acceptable weight and normal blood glucose
concentration and related analytes.
3) If weight remains excessive, repeat steps 1) and 2) until acceptable weight is slowly
achieved.
F. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of CH2O, fat, protein, energy, minerals, and vitamins before each blood test.
not available.
G. Clinical Summary
A. Example 1
Establish and fill prescription for 1-month-old infant weighing 4 kg using Recommended Daily
Nutrient Intakes from Table 16-1, p 305, and average nutrient contents from Tables 16-3 and 16-
4, p 308.
Energy 130 kcal/kg x 4 kg = 520 kcal/day
Fat 30% of 520 kcal = 156 kcal ÷ 9 kcal/g fat = 17.3 g/day
Protein 10% of 520 kcal = 52 kcal ÷ 4 kcal/g protein = 13.0 g/day (3.25 g/kg)
CH2O 60% of 520 kcal = 312 kcal ÷ 4 kcal/g CH2O = 78 g/day
Fluid 1.5 mL x 520 kcal = 780 mL

Medical Food Mixture Measure Fat
Protein CH2O Energy
(g) (g) (g) (kcal)
ProViMin Powder 5g 0.1 3.6 0.1 16
Polycose Powder 83 g 0.0 0.0 78.0 315
Add water to make 26 oz total volume (769 mL). Offer additional water ad libitum.
Total per day 17.1 13.0 78.1 522

Total per kg -- 3.3 -- 130
Percent Energy 29.5 10 59.8 ---
Approximate osmolarity is < 250 mosm/L. Estimated potential renal solute load is < 150 mosm.
3. Feeding Schedule:
a. Divide feedings equally and feed every 3 to 4 hours or as needed (12, 43). Each feeding
of above formula mixture provides 3 g CH2O/fl oz.
b. As child grows and pancreatic amylase activity normalizes, raw cornstarch may be
substituted for Polycose to fill CH2O requirements.
B. Example 2
Establish and fill prescription for 5-year old weighing 18 kg using Recommended Daily Nutrient
Intakes from Table 16-1, p 305, and nutrients from Tables 16-3 through 16-5, p 308.
Energy = 1,300 kcal/day
Fat 25% of 1300 kcal = 325 kcal ÷ 9 kcal/g fat = 36.0 g/day
Protein 10% of 1300 kcal = 130 kcal ÷ 4 kcal/g protein = 32.5 g
CH2O 65% of 1300 kcal = 845 kcal ÷ 4 kcal/g CH2O = 211 g
Nocturnal infusion 25% of 1300 kcal = 325 kcal as CH2O ÷ 4 kcal/g CH2O = 81.25 g
Total CH2O feeds 211 g/d - 81.25 g nocturnal = 130 g CH2O daytime
Raw cornstarch to be given as 2.0 g/kg body weight/feed as part of total CH2O prescription.
Fluid = 1,300 mL
Medical Food Mixture Measure Fat Protein CH2O Energy
(g) (g) (g) (kcal)
ProViMin Powder 17 g 0.2 12.4 0.34 53
Raw cornstarch1 15 Tbsp (120 g) 0.0 0.0 130.00 540
Add water to make 21 fl oz total volume (621 mL). Offer additional fluid ad libitum.
Total daytime feeds 36.2 32.4 130.4 998

1
Raw cornstarch should be added to RCF/ProViMin mix in 1:2 ratio. Additional water may be added to
RCF or ProViMin if needed to meet 1:2 ratio criterion. Supply raw cornstarch (2.0 g/kg body
weight/feed) divided throughout day.
3. Nocturnal infusion using Polycose powder
Carbohydrate Source Measure CH2O Energy
(g) (g)
Polycose Powder 86 g 81.2 327
Add water to make 600 mL
Infuse at 60 mL/hr for 10 hours (600 min)
Calculation for glucose/kg/min
81.2 g CH2O x 1000 mg/g = 81,200 mg
81,200 mg CH2O ÷ 18 kg BW ÷ 600 min = 7.5 mg glucose/kg/min

TABLE 16-1. Recommended Daily Nutrient Intakes (Ranges) for Infants and Children with Glycogen
Storage Disease Type I
Age Nutrient
1
Energy Fat Protein CH2O Fluid2
(kcal/kg) (% of energy) (% of energy) (% of energy) (mL/kg)
Infants
0 to < 3 mo 120 (145-95) 25 - 35 10 - 15 60-70 150-125
3 to < 6 mo 115 (145-95) 25 - 35 10 - 15 60-70 160-130
6 to < 9 mo 110 (135-80) 25 - 35 10 - 15 60-70 145-125
9 to < 12 mo 105 (135-80) 25 - 35 10 - 15 60-70 135-120
(kcal/day) (% of energy) (% of energy) (% of energy) (mL/day)

Girls and Boys
1 to < 4 yr 1,300 (900-1800) 25 - 35 10 - 15 60-70 900 - 1800
4 to < 6 yr 1,700 (1300-2300) 25 - 35 10 - 15 60-70 1,300 - 2,300
7 to < 11 yr 2,400 (1650-3300) 25 - 35 10 - 15 60-70 1,650 - 3,300
Women
11 < 15 yr 2,200 (1500-3000) 25 - 35 10 -15 60 - 70 1,500 - 3,000
15 < 19 yr 2,100 (1200-3000) 25 - 35 10 -15 60 - 70 1,200 - 3,000
> 19 yr 2,100 (1400-2500) 25 - 35 10 -15 60 - 70 1,400 - 2,500
Men
11 < 15 yr 2,700 (2000-3700) 25 - 35 10 -15 60 - 70 2,000 - 3,700
15 < 19 yr 2,800 (2100-3900) 25 - 35 10 -15 60 - 70 2,100 - 3,900
> 19 yr 2,900 (2000-3300) 25 - 35 10 -15 60 - 70 2,000 - 3,300
1
2
older infants and children for each kcal ingested.

TABLE 16-2. Fructose-, Sucrose-, and Galactose-Restricted Diet
Foods Allowed Foods Restricted
BEVERAGES
Coffee, RCF ® Ross Carbohydrate-Free Soy Formula All milk and milk products with added fructose, fruit,
Base With Iron, ProViMin ® Protein-Vitamin-Mineral or flavors that contain honey, molasses, or sugar;
Formula Component With Iron Powder, ProMod ® beer; brandy; rum; vodka; carbonated beverages
Protein Supplement, tea, artificially sweetened containing fructose, fruit juice, or sugar; fruit juices
beverages, soy milk products made without sucrose or drinks containing fruit juice; liqueur; sherry;
or fructose, nondairy creamers (without sugar) vermouth
BREADS, CEREALS, AND GRAINS

All None
CHEESES AND OTHER MILK PRODUCTS

Aged cheese, butter, buttermilk (fermented), or yogurt
DESSERTS
Those made with glucose hydrolyzed corn starch, Any made with milk, milk products, fructose, fruit,
corn syrup, or Polycose ® Glucose Polymers and fruit juice, high fructose corn syrups, honey,
without milk or milk products molasses, or sugar; cakes, pies, or pastries
containing sucrose or lactose (galactose)
EGGS
All Any to which fructose, fruit, high fructose corn syrup,
honey, molasses, or sugar has been added.
FATS
Bacon; butter, margarines and salad dressings that do Mayonnaise and salad dressings with added
not contain milk/milk products; lard; non-dairy coffee fructose, fruit, high fructose corn syrup, honey,
creamers free of fructose, high fructose syrup, honey, molasses, or sugar; milk products; sour cream
molasses, and sugars; oils; shortening; whipping
cream
FRUITS/JUICES
Avocado, raw lemons (limited), rhubarb; limited All others
amounts of gooseberries, loganberries, blackberries,
cranberries, currants, pomegranates, limes
LEGUMES (BEANS & PEAS), NUTS, AND SEEDS

All None
MEAT, FISH AND OTHER SEAFOOD, AND POULTRY

Plain meat, fish and other seafood; poultry; pork, veal Any to which honey, molasses, syrup, or milk/milk
products is added in processing or cooking
SUGARS/SWEETENERS
NutraSweet ® (Aspartame); Sweetmate ® Any containing fructose, high fructose corn syrup,
(acesulfame K), Splenda ® (sucralose) honey, molasses, sugar

Foods Allowed Foods Restricted
VEGETABLES
All None
MISCELLANEOUS
Bakers cocoa; bitter chocolate; monosodium Carob powder; catsup; chile sauces; chocolate milk
glutamate (MSG); pure seasonings and spices; or sweets; drugs, mineral/vitamin preparations
dextrin; glucose, maltose; Polycose ® Glucose containing fructose, sorbitol, or sugar; seasonings
Polymers; Pro-Phree ® Protein-Free Energy Module containing added fructose, high fructose syrup;
with Iron, Vitamin and Mineral supplements not honey, molasses, sugar; maple syrup; jams; jellies;
containing fructose, or lactose preserves
From reference 25.
Galactose-restricted foods modified from references 18, 19, 20.

TABLE 16-3. Major Nutrients in RCF ® Ross Carbohydrate-Free Soy Formula Base With Iron and ProViMin
® Protein-Vitamin-Mineral Formula Component With Iron
Nutrient RCF 1 ProViMin 2

(Per 100 mL) (Per 100 g powder)
Energy, kcal 81 312
Protein, g 4.0 73.0
Fat, g 7.2 1.4
Linoleic acid, g 0.81 0
α-Linolenic acid, g 0.04 0
1
Concentrated.
2
Approximate weights per g powder of ProViMin measured in level, dry US standard household measures:
1 Tbsp = 2.9 g
1/4 cup = 11 g
2/3 cup = 30 g
1 cup = 44 g
1
TABLE 16-4. Serving List of Foods
Food List Serving Size Fat Protein CH2O Energy

(approx) (g) (g) (g) (kcal)
Carbohydrate
Starch 1/2 cup <1 3 15 80
Other carbohydrates varies varies varies 15 varies
Fat 5 -- --- 45
Meat and meat substitutes
Very lean 1 oz 0-1 7 --- 35
Lean 1 oz 3 7 -- 35
Vegetables 1/2 cooked, --- 2 5 25
1 cup raw
1
From reference 2.
TABLE 16-5. Nutrient Composition of Raw Cornstarch

Nutrient Raw Cornstarch
(per Tbsp; 8 g)
Energy, kcal 36
Carbohydrate, g 8.7

TABLE 16-6. Diet Guide for Glycogen Storage Disease Type I
Name:_____________________________ Date: _______/_______/_______ Weight: ______________________ kg

Mo Day Year
MEDICAL FOOD MIXTURE Amount Fat Protein CH2O Energy
(g) (g) (g) (kcal)
RCF Concentrate, mL
ProViMin, g
Add water to make ________________ oz/mL (fl oz) Amount of CH2O /kg/feed ________________
Daily Intake Servings Fat Protein CH2O Energy

(g) (g) (g) (kcal)
BREAKFAST
Medical Food Mixture
Starch
Other Carbohydrate
Meat
Fat
MIDMORNING SNACK
LUNCH
Starch
Other Carbohydrate
Vegetables
Meat
Fat
MIDAFTERNOON SNACK
DINNER
Starch
Other Carbohydrate
Vegetables
Meat
Fat
BEDTIME SNACK
NOCTURNAL FEEDS
(g CH2O/kg/feed or
mg CH2O/kg/min)
DAILY TOTALS
Comments:
Nutritionist

310 Glycogen Storage Disease
TABLE 16-7. Glycogen Storage Disease Type I Clinical Summary Sheet

Mo Day Year

nighttime
feeding
Lt/Ht Wt HC GLU Plasma Serum Lactate Uric Acid Albumin Hct Hgb Fat Pro CH2O Energy GLU
1
TAG Chol [P/S] [P/S] (g) (g) (g/kg)
mo/d/yr (cm) (kg) (cm) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (mg/dL) (g/dL) (%) (g/dL) % energy % energy % energy (kcal) (mg/kg/min)
1
Triacylglycerol
REFERENCES
1. Ambruso DR, McCabe ERB, Anderson D, et al: Infectious and bleeding complications in patients with glycogenosis
type Ib. Am J Dis Child 1985;139:691-697.
2. American Dietetic Association. Exchange Lists for Meal Planning. Chicago: American Dietetic Association, 1995.
Dis 2000;23 Suppl 1:29A.
1996.
5. Bier DM, Leake RD, Hayward MW, et al: Measurement of "true" glucose production rates in infancy and childhood
with 6,6-dideuteroglucose. Diabetes 1977;26:1016-1023.
6. Chen YT: Type I glycogen storage disease: Nine years of management with cornstarch. Eur J Pediatr 1993;152
(Suppl 1): S56-S59.
7. Chen YT:: Glycogen storage diseases. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of Inherited
Disease, ed 8. New York: McGraw-Hill Medical Publishing Division, 2001, pp 1521-1552
8. Chen YT, Cornblath M, Sidbury JB: Cornstarch therapy in type I glycogen storage disease. N Engl J Med
1984;310:171-175.
9. Fernandes J: The effect of disaccharides on the hyperlactacidaemia of glucose-6-phosphatase-deficient children.
Acta Paediatr Scand 1974;63:695-698.
10. Fernandes J, Alaupovic P, Wit JM: Gastric drip feeding in patients with glycogen storage disease type I: Its effects
on growth and plasma lipids and apolipoproteins. Pediatr Res 1989;25:327-331.
11. Fernandes J: Leonard JV, Moses SW, et al: Glycogen storage disease: Recommendations for treatment. Eur J
Pediatr 1988;147:226-228.
12. Fernandes J, Smit GMA: The glycogen storage diseases. In Fernandes J, et al (eds). Inborn Metabolic Diseases:
Diagnosis and Treatment, ed 3. New York: Springer, 2000, pp 314-318.
13. Fomon SJ, Ziegler EE: Water and renal solute load. In Fomon SJ (ed) Nutrition of Normal Infants. St.Louis: Mosby
Books, 1993.
15. Gitzelmann R, Bosshard NU: Defective neutrophil and monocyte functions in glycogen storage disease type Ib: A
literature review. Eur J Pediatr 1993;152 (Suppl 1):S33-S38.
16. Goldberg T, Slonim AE: Nutrition therapy for hepatic glycogen storage diseases. J Amer Diet Assoc 1993;93:1423-
1430.
17. Greene HL, Slonim AE, Burr IM, Moran JR: Type I glycogen storage disease: Five years of management with
nocturnal intragastric feeding. J Pediatr 1980;96:590-595.
18. Gropper SS, Olds SJ, Gross KC: The galactose content of selected fruits and vegetable baby foods: Implications
for infants on galactose-restricted diets. J Amer Diet Assoc 1992;92 (Suppl):A-30.
19. Gross KC: Changes in free galactose, myo-inositol, and other monosaccharides in normal and non-ripening
mutant tomatoes. Phytochemistry 1983;22;1137-1139.
20. Gross KC, Acosta PB: Fruits and vegetables are a source of galactose: Implications in planning the diets of
patients with galactosaemia. J Inher Metab Dis 1991;14:253-258.
21. Hayde M, Windhalm K: Effects of cornstarch treatment in very young children with type I glycogen storage
disease. Eur J Pediatr 1990;149:630-633.
22. Kelly WN, Rosenbloom FM, Seegmiller JE, Howell RR: Excessive production of uric acid in type I glycogen
storage disease. J Pediatr 1968;72:488-496.
23. Lee PJ, Patel JS, Fewtrell M, et al: Bone mineralization in Type I glycogen storage disease. Eur J Pediatr
1995;154:483-487.
24. MacLean W, Graham G: Pediatric Nutrition in Clinical Practice. Menlo Park, Calif: Addison-Wesley Publishing, Co,
1982.
Home Economics Research Report No. 48. US Govt Printing Office, 1987.
26. Meites S (ed): Pediatric Clinical Chemistry: Reference Normal Values, ed 3. Washington, DC: AACC Press, 1989.
27. Moses S: Pathophysiology and dietary treatment of the glycogen storage diseases. JPEN 1990;11:155-174.
28. Parker PH, Ballew M, Greene HL: Nutrition management of glycogen storage disease. Ann Rev Nutr
1993;13:83-109.
29. Perlman M, Aker M, Slonim AE: Successful treatment of severe type I glycogen storage disease with neonatal
presentation by nocturnal intragastric feeding. J Pediatr 1979;94:772-774.
30. Slonim AE, Terry A, Lacy WW, et al: Nocturnal intragastric therapy in type I glycogen storage disease: Effect on
hormonal and amino acid metabolism. Metabolism 1979;28:707-715.
31. Smit GPA, Berger R, Potasnick R, et al: The dietary treatment of children with type I glycogen storage disease with
slow release carbohydrate. Pediatr Res 1984;18:879-881.

32. Smit GPA, Ferndandes J, Leonard JV, et al: The long-term outcome of patients with glycogen storage diseases.
1976.
1983;7:280-288.
35. Stanley CA, Mills JL, Baker L: Intragastric feeding in type I glycogen storage disease: Factors affecting the control
of lactic acidemia. Pediatr Res 1981;15:1504-1508.
36. Tietz NW (ed): Fundamentals of Clinical Chemistry. Philadelphia, PA: WB Saunders Company, 1976.
37. Ullrich K, Smit GPA: Clinical aspects of glycogen storage disease type I. Summary of the discussions. Eur J
Pediatr 1993;152 (Suppl 1):S87-S88.
38. Vici CD, Bartuli A, Mazziotta MRM, Sabetta G: Early introduction of uncooked cornstarch for treatment of glycogen
storage disease type I. Acta Paediatr Scand 1990;79:978-979.
39. Viega-da-Cunha M, Gerin I, van Schaftigen E: How many forms of glycogen disease type I. Eur J Pediatr
2000;159:314-318.
40. Visser G, Herwig J, Rake JP: Neutropenia and neutrophil dysfunction in glycogen storage disease type Ic. J Inher
Metab Dis 1998;21:227-231.
41. Visser G, Rake JP, Fernandes J, et al: Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in
glycogen storage disease type Ib: Results of the European study on glycogen storage disease type I. J Pediatr
2000;137;187-191.
42. Wendel U, Schroten H, Burdach S, Wahn V: Glycogen storage disease type Ib: Infectious complications and
measures for prevention. Eur J Pediatr 1993;152 (Suppl 1):S49-S51.
43. Wolfsdorf JI, Ehrlich S, Landy HS, Crigler JF: Optimal daytime feeding regimen to prevent postprandial
hypoglycemia in type I glycogen storage disease. Am J Clin Nutr 1992;56:587-592.
44. Wolfsdorf JI, Plotkin RA, Laffel LMB, Crigler JF: Continuous glucose for treatment of patients with type I glycogen
storage disease: Comparison of the effects of dextrose and uncooked cornstarch on biochemical variables. Am J
Clin Nutr 1990;52:1043-1050.
45. Yudkoff M, Nisim I, Stanley C, et al: Glycogen storage disease: Effects of glucose infusions on [15N] glycine
kinetics and nitrogen metabolism. J Pediatr Gastroenterol Nutr 1984;3:81-88.

PROTOCOL 17 — Hereditary Fructose Intolerance
Nutrition Support of Infants, Children, and Adults

I. Introduction
Hereditary fructose intolerance (HFI) is caused by a deficiency in activity of fructose-1-phosphate
aldolase (aldolase B) (Figure P), an enzyme normally present in liver, intestine, and kidney cortex (1,
6, 9, 13, 14). Incidence has been estimated at 1/20,000 to 1/40,000 live births (19).
Glycogen
Glucose
Sorbitol Glucose-6-phosphate
Sorbitol dehydrogenase
Hexokinase
Sucrose Fructose Fructose-6-phosphate
Fructokinase
Fructose-1-phosphate* Fructose-1:6-diphosphate*
Fructoaldolase B Fructoaldolase B
Glyceraldehyde Dihydroxyacetone phosphate Glyceraldehyde-3-phosphate
2-phosphoglycerate
= site of enzyme malfunction
* Accumulates in untreated HFI
Pyruvate/lactate
Figure P. Fructose metabolism in hereditary fructose intolerance

Fructoaldolase B deficiency results in accumulation of fructose-1-phosphate in tissues that possess
fructokinase, which causes depletion of inorganic phosphate and ATP. Whether liver and renal
impairment is due to the toxic effect of fructose-1-phosphate, the fall in tissue ATP content, or both, is
unclear. Fructose-induced hypoglycemia results from inhibition of both gluconeogenesis and
glycogenolysis (6). Interaction of phosphorylase a with its substrates, glycogen and inorganic
phosphate, is blocked after fructose administration, and this block could result from a combination of
ATP depletion and direct inhibition of activation of phosphorylase a by fructose-1-phosphate. Such an
inhibition explains why fructose-induced hypoglycemia cannot be corrected by administration of
glucagon (20, 31).
Symptoms appear only when fructose, sucrose, or sorbitol is introduced into the diet (10). Symptoms
are not specific, so diagnosis may be overlooked. Symptoms may occur early in life and be severe;
later they are less marked as the child develops an aversion to sweets (31).
Vomiting is such a constant finding that its absence in a subject ingesting fructose argues against the
diagnosis. Poor feeding, diarrhea, and later, failure to thrive are less frequent. Some manifestations
reflect liver impairment: hepatomegaly, bleeding tendency, jaundice, edema or ascites (11, 12).
Postprandial hypoglycemic manifestations such as pallor, seizures, and shock are infrequent; they are
318 Hereditary Fructose Intolerance © 2001 Ross Products Division

present in about one-third of patients and occasionally lead the pediatrician to suspect fructose
intolerance (31).
The main laboratory findings concern dysfunction of the liver. These are frequent and severe in
infants with early clinical manifestations and may be lacking later: deficient clotting factors with
occasional pattern of consumption-CoAgulopathy, hypoalbuminemia, hypocholesterolemia, increased
transaminase activity, elevated blood concentrations of tyrosine (TYR) and methionine (MET), and
hyperbilirubinemia. Other findings such as moderate proteinuria, glucosuria, generalized
hyperaminoaciduria, metabolic acidosis with loss of bicarbonate, and high urinary pH are due to renal
proximal tubular dysfunction (31). Histologic examination of liver after clotting factors have returned to
normal shows fibrosis without evidence of inflammation, diffuse fatty vacuolization in liver cells, and
necrosis of a few scattered hepatocytes (31).

Some infants with severe liver failure may die if the diagnosis is overlooked (8). In the majority of
cases, outcome is excellent. With a fructose-free diet, vomiting disappears immediately, as does the
bleeding tendency, in less than 24 hours. The renal tubular dysfunction disappears 2 or 3 days later,
and the general condition improves within a few days. All the clinical and laboratory findings are
normal within 1 or 2 weeks, except for hepatomegaly which persists for many years. Normal growth in
length and weight is reached within 2 or 3 years. Liver biopsy shows rapid disappearance of
intralobular fibrosis and a decrease of periportal fibrosis; in contrast, fatty vacuolization of liver cells
persists or increases and its distribution changes from the diffuse to the periportal type. Hepatomegaly
and steatosis disappear with the fructose-free diet between the ages of 5 and 10 years (31).

A. The Defect
1. HFI results from defect in fructoaldolase (aldolase B) in liver, kidney cortex, and small
intestine (9-11).
B. Clinical Evaluation (16, 17, 19, 24, 27, 28, 33)
1. Infants or children who have any of the following clinical or laboratory signs should be
evaluated for HFI.
a. Acute exposure:
1) Apathy, lethargy, coma, convulsions, dizziness, nausea, sweating, trembling, vomiting.
b. Chronic exposure:
1) Abdominal distention, diarrhea, drowsiness, apathy, edema, ascites, failure to thrive,
hemorrhages, hepatomegaly, jaundice, incessant crying or irritability, poor feeding,
poor growth, vomiting (7).
2. Protracted exposure to fructose results in fibrosis, steatosis, cirrhosis of liver, and aversion to
sweets.
3. Laboratory findings:
a. Urinary:
1) Increased amino acids, bicarbonate; ± increased fructose; increased glucose, lactate,
phosphorus, potassium, protein, and urate.
b. Blood:
1) Increased bilirubin, fructose, lactate, liver enzymes, MET, TYR, and urate
2) Decreased bicarbonate,-CoAgulation factors, glucose, pH, phosphorus, potassium,
and proteins.
c. Anemia, thrombocytopenia.
1. Molecular analysis of DNA is safest method of diagnosis (1, 2, 4-6, 13, 15-22, 30-32).
2. Assay of aldolase B activity in liver tissue obtained by needle biopsy when liver insufficiency
has regressed after initiation of fructose-free diet (27).
IV. Rationale For Nutrition Support

A. Correct primary imbalance in Metabolic Relationships
1. Remove or restrict fructose, sorbitol, and sucrose to lowest amount compatible with
nutritionally adequate diet.
© 2001 Ross Products Division Hereditary Fructose Intolerance 319

A. Growth and Nutrition Status
in adults.
b. Avoid prolonged fasting.
B. Laboratory Indices
1. Maintain normal blood concentrations of:
a. Bicarbonate.
b. Coagulation factors.
c. Glucose, lactate.
d. Liver enzymes.
e. MET, TYR.
f. Phosphorus, potassium.
g. Proteins.
h. Urate.
2. Maintain normal liver and renal function.

A. Fructose, Sorbitol, Sucrose
1. Remove all foods containing fructose, sorbitol, or sucrose from diet until 3 years of age (3).
2. After age 3 years, 10 to 20 mg/kg body weight may be ingested if growth, laboratory indices
and liver and renal functions remain normal (26, 33).
B. Protein
1. Recommended Daily Nutrient Intakes are somewhat higher than for normal infants, children,
and adults (Table 17-1, p 319).
2. Protein intakes may be up to 2 times recommended without any adverse effects if liver
function is normal.
C. Energy
1. Recommended Daily Nutrient Intakes are same as for normal infants, children, and adults
(Table 17-1, p 319).
2. Intake should be sufficient to maintain normal weight gain in infants and children and maintain
appropriate weight for height in adults.
D. Fluid
2. Requirements may be higher than recommended secondary to fever.

A. Fructose, Sorbitol, Sucrose
1. See Table 17-2, p 320 for foods allowed and excluded (25, 28, 29).
a. For information on nutrient content of beikost (baby food), contact the following
manufacturers:
1-800-233-2468 1-800-443-7237 Pittsburgh, PA 15219
1-800-872-2229

b. Up-to-date lists of product ingredients are necessary to determine which foods may be
included since ingredients change often. Request both nutrient composition and
ingredients list.
B. Protein
1. Calculate amount of Similac ® With Iron (use until 2nd birthday), beikost, whole cow's milk, or
table foods (Tables 17-3 to 17-5, pp 321-321) required to fill protein prescription.
a. Protein intakes up to 2 times greater than Recommended Dietary Allowances (RDAs) (18)
are not cause for concern unless liver function is abnormal.
2. Add beikost or table foods to provide variety in taste, color, and texture after infant is 3 to
4 months old or is developmentally ready (Table 17-5, p 321, for appropriate portion sizes).
C. Energy
1. Calculate energy provided by Similac, beikost, whole cow's milk, or table foods (Tables 17-3
to 17-5, pp 321-321) required to fill energy prescription.
2. If energy prescription is not met, increase number of food servings.
D. Fluid
1. If Similac powder or concentrated liquid is prescribed, mix to obtain formula that provides
20 to 27 kcal/fl oz (Table 17-4, p 321).
2. See Table 17-5, p 321, for approximate amount of Similac to offer.
3. Offer infants additional fluid between Similac feeds of >20 kcal/fl oz.
E. Diet Guide
1. Provide parents, caretakers or patient with completed Diet Guide (Table 17-6, p 322) with
each diet change.

2. Check diet to determine if it supplies RDIs of protein, minerals, and vitamins.
a. See Table 17-1, p 319, and Appendices 6, 13 and 14, pp A-7, A-14 and A-15.
not available.
c. If diet provides < 100% of RDIs, supplement diet if laboratory tests indicate need.
Vitamins A, C, and folate may be low.
d. Care must be taken to ensure that supplements do not contain fructose, sorbitol, or
sucrose.

A. Protein Status
1. Evaluate plasma albumin concentration every 3 months until patient is 1 year of age and twice
2. If plasma albumin concentration is below normal for age:
a. Increase prescribed amount of protein by 5% to 10% and reevaluate plasma albumin
b. If plasma albumin concentration remains low, repeat above process until concentration is
in normal range.
B. Iron Status
b. If plasma ferritin concentration is below normal for age:
1) Increase iron intake to 2 mg/kg body weight with supplements (ferrous sulfate)
2) Evaluate plasma ferritin concentration monthly.
3) Continue iron supplements until plasma ferritin is in normal range.

a. Evaluate hemoglobin and hematocrit concentrations at 6, 9, and 12 months of age and
C. Growth Status
1. Length/height and weight
a. Measure monthly until patient is 1 year old, every 3 months to 4 years of age, and every
6 months thereafter. Plot measurements for infants and children on NCHS growth charts.
infants and children will fall above or below these percentiles. If length/height or weight
falls below usual growth channel:
1) Increase prescribed protein and energy by 5% to 10% and remeasure after 1 month.
2) If length/height or weight remains low, check to make sure all fructose, sorbitol, and
sucrose are deleted from diet and repeat above process until usual growth channel is
achieved.
D. Nutrient Intake
1. Maintain records of food intake for 3 days monthly (Appendices 24 and 25, pp A-26 and A-27).
2. Evaluate intakes of protein, energy, minerals, and vitamins. Determine if foods used contain
any fructose, sorbitol or sucrose.
3. If diet provides < 100% of RDIs, supplement with needed minerals, and vitamins if not
provided by beikost or table foods and if laboratory test results indicate need. Vitamins A, C,
and folate may require supplementation.
E. Clinical Summary.
management (Table 17-7, p 323)
A. Example 1
Intakes from Table 17-1, p 319, and average nutrient content from Table 17-3 through 17-5,
p 321-321.
Protein 3.0 kg x 3.5 kg = 10.5 g
(g) (kcal)
1
Similac with Iron 24 Ready to Feed 530 mL 10.1 490

Approximate osmolarity of medical food mixture is <450 mosm/L. Estimated potential renal solute load is
< 75 mosm.
1
To meet energy needs, 175 mL of Similac (20 kcal/fl oz) per kg of body weight must be fed. If infant will
not ingest 175 mL Ready to Feed Similac/kg, use Similac Concentrated Liquid and dilute to make
24-27 kcal/fl oz.
2
If 2.9 g protein/kg not tolerated, lower protein to 2.2 g/kg and use Pro-Phree ® (Appendix 11, p A-10) to
help supply energy, minerals and vitamins.

A. Rationale
1. Infectious illness and trauma both cause catabolism of body protein (34).
2. Well-nourished persons with HFI respond to infection and trauma as do normal persons.

a. Enhance energy intake when possible by offering Polycose ® Glucose Polymers liquid or
powder (Appendix 9, p A-9) or Pro-Phree ® Protein-Free Energy Module With Iron,
Vitamins & Minerals (Appendix 11, p A-10) added to water or Pedialyte, if tolerated.
b. Return patients to Similac or usual diet as rapidly as possible.
1) Begin with 1/2 original strength of Similac formula
XII. Prescription and Over-The-Counter Medications

A. Contact local pharmacist or drug manufacturer for current information on excipients in drugs that
may contain fructose, sorbitol or sucrose.
B. Sucrose was present in 63% of vitamin and mineral preparations evaluated and sorbitol was also
added to some products (23).

TABLE 17-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults with
Hereditary Fructose Intolerance
Age Nutrient
1
Infants
0 to < 3 mo 3.0 < 4.5 120 (145 - 95) 150 - 125
3 to < 6 mo 3.0 < 4.5 115 (145 - 95) 160 - 130
6 to < 9 mo 2.5 < 4.0 110 (135 - 80) 145 - 125
9 to < 12 mo 2.5 < 4.0 105 (135 - 80) 135 - 120

Girls and Boys
1 to < 4 yr 30 < 60 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 35 < 70 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 40 < 80 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to <15 yr 50 < 100 2,200 (1500 - 3000) 1,500 - 3,000
15 to <19 yr 50 < 100 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr 50 < 100 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to <15 yr 60 < 120 2,700 (2000 - 3700) 2,000 - 3,700
15 to <19 yr 65 < 130 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr 65 < 130 2,900 (2000 - 3300) 2,000 - 3,300
1
2
Under normal circumstances, offer a minimum of 1.5 mL fluid to neonates and 1.0 mL to children and adults for each
kcal ingested.

TABLE 17-2. Fructose-, Sorbitol- and Sucrose-Restricted Diet (3)
Foods Allowed Foods Excluded

BEVERAGES
Buttermilk, evaporated milk; coffee; cow's milk; human Any milks with added fructose, fruit, or flavors that contain
milk; RCF ® Ross Carbohydrate-Free Soy Formula Base honey, molasses, sorbitol or sugar; beer; brandy; rum;
With Iron; Similac ® Infant Formula With Iron; tea vodka; carbonated beverages containing fructose, fruit
juice, molasses, sorbitol or sugar; fruit juices or drinks
containing fruit juice; liqueur; sherry; vermouth
BREADS, CEREALS AND GRAINS

Corn, cornmeal, corn cereals; breads, some French and All bran; breads or cereals containing fruit, nuts, honey,
Italian breads without added sugar, pumpernickel or rye; molasses, sugar, sorbitol, or high fructose corn syrup;
flour, refined white; oats, oatmeal; pastas made with Prepared cereals such as cornflakes, Grapenuts, muesli,
refined flour; rice, brown or white, rice cereals; Rye Crisp; Rice Krispies, sugar puffs, containing fruits, nuts, honey,
tortillas, flour; wheat germ; wheat, shredded molasses, sugar, sorbitol, or high fructose corn syrup
CHEESES/OTHER MILK PRODUCTS

Cheese: cheddar, cottage, cream, mozzarella, Neufchatel, Ice cream; ice milk; shakes; sherbets; yogurt with fructose,
ricotta, Swiss, pasteurized cheese food (American) all fruit, honey, molasses, sorbitol or sugar
without fructose, sorbitol, or sugar; calcium and sodium
caseinates; cream; whey; yogurt (plain)
DESSERTS
None unless made with glucose, hydrolyzed corn starch, Any made with fructose, fruit, fruit juice, high fructose corn
corn syrup, or Polycose ® Glucose Polymers syrups, honey, molasses, sorbitol, or sugar
EGGS
All Any to which fructose, fruit, high fructose corn syrup,
honey, molasses, sorbitol or sugar has been added
FATS
Bacon; butter; cream; cream cheese; lard; margarines; Mayonnaise and salad dressings to which fructose, fruit,
non-dairy coffee creamers free of fructose, high fructose high fructose corn syrup, honey, molasses, sorbitol or
corn syrup, honey, molasses, sorbitol and sugar; oils; sugar have been added
shortening
FRUITS/JUICES
Avocado, rhubarb All others
LEGUMES (BEANS & PEAS), NUTS, SEEDS

Tempeh, tofu All others
MEAT, FISH AND OTHER SEAFOOD, POULTRY

Plain meat, fish and other seafood, poultry Any to which fructose, fruit, high fructose corn syrup,
honey, molasses, sorbitol, or sugar is added in processing
or cooking
SUGARS/SWEETENERS
None Any containing fructose, high fructose corn syrup, honey,
molasses, sorbitol, sugar
VEGETABLES
Asparagus; broadbeans, immature; celery; chard, Swiss; All others
cucumber; kale; lettuce; mustard greens; mushrooms;
parsnips; peas, green; potato, white, mature; spinach;
turnip greens; watercress

Foods Allowed Foods Excluded
MISCELLANEOUS
Cornstarch; gelatin without fruit or sugar; dextrin, Carob powder; catsup; chile sauces; chocolate; drugs,
galactose, glucose, maltose, lactose; Polycose ® Glucose mineral/vitamin preparations containing fructose, sorbitol,
Polymers; Pro-Phree ® Protein-Free Energy Module With or sugar; seasonings containing added fructose, high
Iron, Vitamins & Minerals fructose; syrup; honey; molasses; sorbitol; sugar; maple
syrup; jams; jellies: preserves
TABLE 17-3. Exchange Lists for Children and Adults with Hereditary Fructose Intolerance
Food Measure Protein Energy

(g) (kcal)
Cow's milk, whole 8 fl oz. 8.0 240
Meat 1 oz 7.0 75
Fat Varies 0.0 45
Starch/bread Varies 3.0 80
Vegetables2
cooked 1/2 cup 2.0 25
raw 1 cup 2.0 25
Similac ® With Iron, concentrated liquid 100 mL 2.8 136
1
Modified from Exchange Lists for Weight Maintenance. Chicago: The American Dietetic Association, 1995.
2
See Table 17-2 for vegetables to exclude.
TABLE 17-4. Amounts of Similac ® Concentrated Liquid or Powder Required to Make Formulas of 24 or
27 kcal/fl oz
Concentration Similac
Concentrated Liquid Powder
(mL) (water to make) (g) (water to make)
24 kcal/fl oz 71 mL 118 mL1 18.72 118 mL1
27 kcal/fl oz 76 mL 118 mL 21.02 118 mL
1
4 fl oz
2
1 scoop of Similac powder = 8.5 g
TABLE 17-5. Foods that Will Supply Daily Nutrient Needs of Infants with Hereditary Fructose Intolerance
Food/Amount Age of Infant (mo)

0 to <3 3 to <6 6 to <9 9 to <12
1
Similac With Iron, mL/kg 130 - 150 125 - 140 120 - 135 115 - 130
2, 3
Infant cereals, Tbsp/kg 0 1-2 2 2
Meats, pureed, Tbsp/kg 0 0 0.5 - 1 0.5 - 1
2, 4
Vegetables, pureed, Tbsp/kg 0 1 1 1
1
Mix concentrated liquid or powder to yield 24 to 27 kcal/ fl oz.
2
Introduce teaspoon-size portions after infant is 3 to 4 months of age or developmentally ready. Allow 3 to 5 days
between addition of each new food to determine if infant is allergic to it. Gradually increase portion sizes until
recommended amounts are being ingested.
3
Use only cereals free of fruit, fruit juice or sugar.
4
See Table 17-2, p 320, for vegetables to exclude.

TABLE 17-6. Hereditary Fructose Intolerance Diet Guide
Name:_____________________________________________
Date: _________/________/________
Mo Day Year
Birthdate: : _________/________/________ Age: _______________________

Mo Day Year
Length/Height: ____________________ (cm/in) Weight: __________________ (kg/lb)
Medical Food Amount Protein Energy

(g) (kcal)
Similac with Iron mL
Similac with Iron, powder g
mL
mL
Whole milk cups
Add water to make ______________________ mL _______________ (fl oz)
Fat
Meat
Vegetables
Total per day
Total per kg
Comments:
Nutritionist

TABLE 17-7. Hereditary Fructose Intolerance Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

Length/ Weight Head Glucose Potassium Phosphorus Ferritin Albumin Hgb Uric Fructose Protein Energy
Height Circum Acid Sucrose
Sorbitol
(mo/d/yr) (cm) (kg) (cm) (mg/dL) (mEq/L) (mg/dL) (ng/mL) (g/dL) (g/dL) (mg) (g) (g) (kcal)
Hereditary Fructose Intolerance 323
REFERENCES
1. Ali M, Rellos P, Cox TM: Hereditary fructose intolerance. J Med Genet 1988;35;353-365.
2. Ali M, Rosiem U, Cox TM: DNA diagnosis of fatal fructose intolerance from archival tissue. Q J Med 1993;8:25-30.
3. Bell L, Sherwood WG: Current practices and improved recommendations for treating hereditary fructose
intolerance. J Amer Diet Assoc 1987;87:721-728.
4. Brooks CC, Buist N, Tuerck J, Tolan DR: Identification of a splice-site mutation in the aldolase B gene from an
individual with hereditary fructose intolerance. Am J Hum Genet 1991;49:1075-1081.
5. Brooks CC, Tolan DR: A partially active mutant aldolase B from a patient with hereditary fructose intolerance.
FASEB J 1994;8:107-113.
6. Brooks CC, Tolan DR: Association of the widespread A149P hereditary fructose intolerance mutation with newly
identified sequence polymorphisms in the aldolase B gene. Am J Hum Genet 1993;52:835-840.
7. Burmeister LA. Valdivia T, Nuttall FQ: Adult hereditary fructose intolerance. Arch Intern Med 1991;151;773-776.
8. Collins J: Time for fructose solutions to go. Lancet 1993;341-600.
9. Cox TM: Aldolase B and fructose intolerance. FASEB J 1994;8:62-71.
10. Cox TM: Fructose intolerance: Diet and inheritance. Proc Nutr Soc 1991;50:305-309.
11. Cox TM: Hereditary fructose intolerance. Bailliere's Clin Gastroent 1990;4:61-78.
12. Cross NCP, Cox TM: Hereditary fructose intolerance. Intl J Biochem 1990;22:685-689.
13. Cross NCP, Cox TM: Molecular analysis of aldolase B genes in the diagnosis of hereditary fructose intolerance in
the United Kingdom. Q J Med 1989;271:1015-2020.
14. Cross NCP, Cox TM: Partial aldolase B gene deletions in hereditary fructose intolerance. Am J Hum Genet
1990;47:101-106.
15. Dazzo C, Tolan DR: Molecular evidence for compound heterozygosity in hereditary fructose intolerance. Am J Hum
Genet 1990;46:1194-1199.
16. Edstrom CS: Hereditary fructose intolerance in the vomiting infant. Pediatrics 1990;85:600-603.
17. Endres W, Sierck T, Shin YS: Clinical course of hereditary fructose intolerance in 56 patients. Acta Paediatr Jpn
1988;30:452-456.
19. Froesch ER, Wold HP, Baitsch H: Hereditary fructose intolerance. An inborn defect of hepatic fructose-1-
phosphate splitting aldolase. Am J Med 1963;34:151-167.
20. Gopher A, Viasman N, Mandel H, Lapidot A: Determination of fructose metabolic pathways in normal and
fructose-intolerant children: A13C NMR study using [U-13C] fructose. Proc Natl Acad Sci 1990;87:5449-5453.
21. Kaiser UB, Hegele RA: Case report: Heterogeneity of aldolase B in hereditary fructose intolerance. Am J Med Sci
1991;302:364-368.
22. Kajihara S, Mukai T, Arai Y, et al: Hereditary fructose intolerance caused by a nonsense mutation of the aldolase B
gene. Am J Hum Genet 1990;47:S62-S67.
23. Kumar A, Aitas AT, Hunter AG, Beaman DC: Sweeteners, dyes and other excipients in vitamin and mineral
preparations. Clin Pediatr 1996;Sept:443-450.
24. Labrune P, Chatelon S, Huguet P, Odievre M: Unusual cerebral manifestations in hereditary fructose intolerance.
Arch Neurol 1990;47:1243-1244.
Home Economics Research Report No. 48. US Govt Printing Office, 1987.
26. Mock DM, Perman JA, Thaler M, Morris RC: Chronic fructose intoxication after infancy in children with hereditary
fructose intolerance. N Engl J Med 1983;309:764-770.
27. Odievre M: Disorders of fructose metabolism. In Fernandes J, et al (eds): Inborn Metabolic Diseases: Diagnosis
and Treatment. New York: Springer Verlag, 1990, pp 107-112.
28. Odievre M, Gentil C, Gautier M, Alagille D: Hereditary fructose intolerance in childhood. Diagnosis, management
and course in 55 patients. Am J Dis Child 1978;132-605-608.
29. Rumessen JJ: Fructose and related food carbohydrates. Sources, intake, absorption and clinical implications.
Scand J Gastroenterol 1992;27:819-828.
30. Santamaria R, Scarano MI, Esposito G, et al: The molecular basis of hereditary fructose intolerance in Italian
children. Eur J Clin Chem Clin Biochem 1993;31:675-678.
31. Steinmann B, Gitzelmann R, Van den Berghe G: Disorders of fructose metabolism. In Scriver CR, et al (eds): The
2001, pp 1489-1520.
32. Tolan DR, Brooks CC: Molecular analysis of common aldolase B alleles for hereditary fructose intolerance in North
America. Biochem Med Metab Biol 1992;48:19-25.
33. van den Berghe G: Disorders of fructose metabolism. In Fernandes J, et al (eds): Inborn Metabolic Diseases, ed 3.
New York: Springer, 2000, pp 111-116.
34. Wannamacher RW: Key role of various individual amino acids in host response to infection. Am J Clin Nutr
1977;30:1269-1280.
PROTOCOL 18 — Pyruvate Carboxylase Deficiency
Nutrition Support of Infants and Children With

I. Introduction
Pyruvate can be converted to phosphoenolpyruvate (PEP), oxaloacetate (OAA), acetyl-CoA (AcCoA),
alanine, or lactate. The enzymes involved are pyruvate kinase (PK), phosphoenolpyruvate
carboxykinase (PEPCK), pyruvate dehydrogenase (PDH), pyruvate carboxylase (PC), alanine
aminotransferase (AAT), and lactate dehydrogenase (LDH) (10, 32).
LDH
Carbohydrate Pyruvate* Lactate*
AAT
Glucose
PK PC PDH, Alanine*
Biotin Thiamin
AcCoA Fatty Acids

PEPCK
PEP OAA Aspartate
Site of enzyme malfunction

* Accumulates in untreated PC deficiency
Figure Q. Metabolic fates of pyruvate (modified from reference 32)

PC, a biotin-requiring enzyme, is located in the mitochondrial matrix where it catalyzes the first step in
gluconeogenesis and supplies OAA from pyruvate. OAA is in equilibrium with aspartate. PC deficiency
may result from biotinidase deficiency or from a structural change in the PC apoprotein (10, 32).
Aspartic acid, made from OAA, or used to synthesize OAA, may become deficient in severe PC
deficiency. With depletion of aspartate, the urea cycle does not function normally and citrullinemia,
hyperammonemia, and hyperlysinemia result. Aspartate is important in the shuttle mechanism that
transfers reducing equivalents across the mitochondrial membrane. Inadequate concentrations of
aspartate in the cytosol result in an increase in the lactate/pyruvate ratio (9, 10, 32).
Clinical symptoms of PC deficiency are heterogeneous ranging from a severe infantile (A and B) type
to a benign variant (C) (3, 17, 18, 33, 45).

Patients with no PC apoenzyme activity often die in infancy. Patients with milder forms of PC deficiency
(> 10% activity) treated with a moderate carbohydrate and protein and low-fat diet supplemented with
citrate, glutamine (GLUNH2), aspartate, asparagine (ASPNH2), and thiamin have had good outcomes
(4, 17, 33, 39, 45).

A. The Defect
1. Defective functioning of PC results from defective PC apoenzyme, biotinidase deficiency, or
absence of an inhibitor of TPP-ATP phosphoryltransferase (40).
330 Pyruvate Carboxylase Deficiency © 2001 Ross Products Division

1. Any infant or child who presents with the following symptoms should be evaluated for PC
deficiency:
a. Clinical:
1) Anorexia, irritability, lethargy, delayed neurologic development, coma, ± mental
retardation, ± hepatomegaly, hypotonia (4, 8, 15, 16, 30, 32).
b. Laboratory:
1) Metabolic acidosis; α-ketoglutarate in urine; ± elevated lactate/pyruvate ratio;
elevated lactate and pyruvate; ± elevated acetoacetate/ß-hydroxybutyrate ratio;
± elevated blood ammonia; ± hypoglycemia; ± elevated plasma alaniSne (ALA),
citrulline (CIT) (9), lysine (LYS), proline (PRO), absent or decreased PC activity in
cultured skin fibroblasts, leukocytes or hepatocytes.
2. Prenatal diagnosis may be made by measuring PC activity in amniocytes and chorionic villus
cells (4, 6, 8, 12, 14-16, 20, 25, 32).
3. See references 2, 3, 8, 27, 32, 34, 40, 44, and 46 for methods of diagnosis.

1. Provide energy from major nutrients as follows: 15% protein, 50% carbohydrate, 35% fat.
2. Administer sodium bicarbonate as needed to maintain normal acid-base status (2, 7, 10, 19).
B. Stimulate Pyruvate Dehydrogenase Activity.
1. Supplement with oral thiamin (5, 7, 19, 20).
C. Supply Product of Blocked Primary Pathway
1. Supplement with precursors of OAA; ASP, citric acid, GLUNH2 (2, 4, 5, 21, 28).

A. Maintain Following Analytes in Plasma in Ranges Noted or in Normal Range for Age Established
by Laboratory Used:
Analyte
Acetoacetate 0.03 - 0.30 mmol/L
ß-Hydroxybutyrate < 0.100 mmol/L
Citric acid 0.060 - 0.160 mmol/L
Glucose 3.9 - 6.1 mmol/L
Lactate 0.5 - 2.0 mmol/L (37)
Pyruvate 0.035 - 0.100 mmol/L (37)
Ammonia 0 - 35 µmol/L (37)
B. Maintain Following Plasma Amino Acids and Glucose in Ranges Noted or in Normal Range for
Age Established by Laboratory Used:
Amino Acid (37) (µmol/L)
Alanine 163- 653

Arginine 34 - 140
Aspartate 1 -25
CIT 1 - 55
Glutamine 250 - 823
LYS 50 - 254
PRO 50 - 273
C Growth, Development, and Nutrition Status

1. Support normal growth rate in infants and children.
© 2001 Ross Products Division Pyruvate Carboxylase Deficiency 331

b. Avoid prolonged fasting.

A. Energy
3. For infants who sleep more than 4 hours at night, add uncooked Argo ® cornstarch (2 g/kg
body weight) to last feed at night (43).
Warning: Inadequate energy intake will result in growth failure (22).
B. Fat (22)
a. Supply about 35% of total daily energy as fat (11).
1) Prescribe 3% of total energy as linoleic acid and 1.0% as α-linolenic acid.
α-linolenic acid are inadequate.
C. Protein
1. Prescribe amount that supplies about 15% of total energy for infants (Table 18-1, p 332).
D. Carbohydrate
E. Thiamin (15, 16 19, 24, 31, 42)

1. Supplement diet with 32-64 mg/kg of thiamin daily.
F. Citric Acid, L-Arginine, L-ASPNH2, L-ASP , L-GLUNH2 (15, 21, 28, 29, 31, 41)
1. Supplement diet with any or all nutrients listed in F required to maintain plasma citrate
concentrations in normal range.
2. Supplement with citrate daily (up to 7.5 mmol/kg/day, part as sodium and part as potassium
salt) (1) to maintain normal plasma citrate and OAA concentrations.
3. Supplement with following amounts of L-amino acids daily, if required. Modify based on
plasma concentrations.
L-Arginine To maintain normal plasma concentration
L-Asparagine 68 mg/kg
L-Aspartic acid 18 - 360 mg/kg
L-Glutamic acid 52 mg/kg
L-Glutamine 460 mg/kg
G. Biotin Has Not Proven To Be of Benefit in Patients With No PC Activity (35).
H. Fluid
I. Fasting
1. Instruct parents and/or caretakers to prevent infants from fasting > 4 hours, children > 6 hours,
and adults > 8 hours.

A. Fat
1. Determine amount of infant formula with iron, beikost, or table foods (Tables 18-2, p 332, and
18-3, p 333) required to supply about 35% of energy prescription as fat.

B. Protein
1. Calculate grams of protein required to provide about 15% of energy prescription.
2. Determine protein provided by infant formula with iron, beikost, or table foods (Tables 18-2
and 18-3, pp 332 and 333) required to supply fat prescription.
3. Subtract amount determined above from total protein prescription (Table 18-2, p 332).
4. Supply any remaining prescribed protein with ProViMin (Table 6-4, p 118), skim milk
(Appendix 8, A-8), or other fat-free or low-fat protein sources (Table 18-3, p 333).
C. Energy
1. Calculate energy supplied by infant formula with iron (until 1st birthday), beikost, or table
foods required to supply fat and that supplied by ProViMin (Table 18-2, p 332), skim milk
(Appendix 8, A-8), and other protein-containing foods (Table 18-2, p 332).
a. Use infant formula with iron until 2nd birthday to help supply needed iron.
3. Supply remaining prescribed energy with Polycose ® Glucose Polymers powder (23 kcal/Tbsp,
3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9), sugar (48 kcal/Tbsp), beikost, or table
foods containing little or no fat (Tables 18-2 and 18-3 pp 332 and 333).
4. Add beikost or table foods after infant is 3 to 4 months old or is developmentally ready to
provide variety in taste, color, and texture (Table 18-2, p 332).

2. Measure or weigh specified amounts of boiled, cooled water; infant formula; ProViMin;
carbohydrate; citric acid; and L-amino acids into clean containers.
4. Slowly pour specified amount of infant formula, citric acid, and L-amino acids into blender and
continue blending for no longer than 1 to 3 seconds.
5. Dissolve powdered carbohydrate in some of remaining water and pour into ProViMin mixture,
mix well, add water to yield prescribed volume and pour into opaque sterilized nursing bottles
or cups. Prepared formula not used immediately should be refrigerated and used within
24 hours. Shake well before feeding.
8. Store unopened cans at room temperature. Cover opened can and store in dry place (not in
refrigerator). Use within 1 month after opening.
E. Diet Guide
each diet change.
2. If necessary, use uncooked Argo cornstarch (2 g/kg body weight, 1:2 ratio cornstarch to water)
in daytime feeds to prevent hypoglycemia (43).
Warning: Never permit patient to fast > 4 hours if an infant, > 6 hours if child, and less
time if patient is febrile, has diarrhea, or is vomiting.

a. See Table 18-2, p 332, for composition ProViMin, skim milk, and infant formulas with iron.

vitamins (Table 6-4, p 118 and Appendices 13 and 14, pp A-14 and A-15).
formulas.
not available.
c. If ProViMin mixture provides < 100% of RDIs for infants and < 75% for children and
supplements).
B. Osmolarity
b. Osmolarity per gram of ProViMin powder is 2.74 mosm.
adults, or is greater than tolerated by patient, increase water content of prescribed medical
food mixture and recalculate its osmolarity (26).
renal solute load.
capacity as low as 600 mosm/L (36).
recalculate.

A. Protein Status
1. Evaluate plasma albumin concentration every 3 months until patient is 1 year old and every
2. If plasma albumin concentration is below standard:
b. If plasma albumin concentration remains low, repeat above process until value is in
normal range.
B. Iron Status
2) Evaluate plasma ferritin concentration monthly in increased iron intake.
a. Hemoglobin and hematocrit should be evaluated at 6, 9, and 12 months of age and every
C. Growth Status

achieved.
D. Nutrient Intake
and 25, pp A-26 and A-27).
not available.
b. See Appendix 28, p A-29, for information about ordering software for diet evaluation. This
software does not calculate fatty acids.
F. Clinical Summary
A. Example
Intakes from Table 18-1, p 332, and average nutrient content from Tables 18-2 and 18-3, pp 332
and 333.
Protein 420 kcal x 0.15 = 63 kcal ÷ 4 kcal = 15.8 g
Carbohydrate 420 kcal - 210 kcal = 210 kcal ÷ 4 kcal = 52.5 g
Food List Measure Fat Protein Energy
(g) (g) (kcal)
Similac With Iron Ready to Feed 415 mL 16.3 5.8 282
ProViMin 13.7 g 0.0 10.0 43
Soy oil 2 mL 1.8 0.0 16
Polycose Liquid 40 mL 0.0 0.0 80

is < 170 mosm.

A. Rationale
protein (47).
2. Well-nourished patients respond to infection and trauma as do normal persons.

a. Enhance energy intake when possible by offering uncooked Argo ® cornstarch (1:2 ratio
cornstarch to fluid) ad libitum as tolerated, liquid Jell-O ®, Polycose powder or liquid
(Appendix 9, p A-9) added to fruit juices or Pedialyte if tolerated, and caffeine-free soft
drinks (not diet drinks).
1) 1/3 cup Polycose powder may be added to liquid Pedialyte to yield 8 fl oz.
b. Return patient to ProViMin medical food mixture and pre-illness diet as rapidly as
possible.
1) Begin with 1/2 original strength of ProViMin medical food mixture.
c. Feed Polycose solution (5-7 g/kg of carbohydrate) or carbohydrate-containing foods every
2 to 3 hours.
1) If unable to feed every 2 to 3 hours, administer solution of raw cornstarch (2-3 g/kg) to
infants older than 6 months.
2) Begin with very small amounts of raw cornstarch and gradually increase to prevent
gas, bloating and diarrhea.
d. Administer 10% glucose solution intravenously if oral intake cannot be maintained.
a. Add uncooked cornstarch, 2 to 3 g/kg/day to any liquids and feed every 2 to 3 hours (43).

Pyruvate Carboxylase Deficiency
Age Nutrient
1
(% of energy) (% of energy) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 12 - 15 30 - 35 120 (145 - 95) 150 - 125
3 to < 6 mo 12 - 15 30 - 35 115 (145 - 95) 160 - 130
6 to < 9 mo 12 - 15 30 - 35 110 (135 - 80) 145 - 125
9 to < 12 mo 12 - 15 30 - 35 105 (135 - 80) 135 - 120
(% of energy) (% of energy) (kcal/day) (mL/day)
Girls and Boys

1 to < 4 yr 12 - 15 30 - 35 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 12 - 15 30 - 35 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 12 - 15 30 - 35 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 12 - 15 30 - 35 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 12 - 15 30 - 35 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr 12 - 15 30 - 35 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 12 - 15 30 - 35 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 12 - 15 30 - 35 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr 12 - 15 30 - 35 2,900 (2000 - 3300) 2,000 - 3,300
1
2
Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to children and adults for each
kcal ingested.
TABLE 18-2. Average Nutrient Contents of Ross Infant Formulas and Gerber ® Baby Foods1

(g) (g) (kcal)
Cereals, dry, Ready To Serve 1 Tbsp2 0.17 0.25 15
Cereals, with fruit, 2nd and 3rd Foods, jarred 1 Tbsp2 < 0.10 0.16 11
2
Desserts: 2nd and 3rd Foods 1 Tbsp < 0.04 0.11 12
2
Fruits, 1st, 2nd and 3rd Foods 1 Tbsp 0.00 0.09 10
Fruit, juice 1 fl oz 0.00 0.07 16
Meat with gravy, 2nd and 3rd Foods 1 Tbsp2 0.67 1.58 14
2
Vegetables: 1st, 2nd and 3rd Foods 1 Tbsp 0.04 0.20 6
3
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed 100 mL 3.74 1.86 68
3
Isomil ® Soy Formula With Iron, Ready to Feed 100 mL 3.70 1.66 68
4
Milk, skim 100 mL 0.19 3.53 36
ProViMin ® Protein-Vitamin-Mineral Formula Component With Iron 100 g 2.00 73.00 312
Similac ® With Iron, Ready to Feed 3 100 mL 3.65 1.40 68
1
2
3
See Appendices 4 through 7, pp A-4 to A-7, for complete nutrient composition.
4
See Appendix 8, p A-8 for complete nutrient composition.

TABLE 18-3. Exchange Lists for Nutrition Support of Children and Adults With Pyruvate Carboxylase
Deficiency1

(g) (g) (kcal)
Meat, lean 1 oz 3 7 55
Milk, skim 1 cup trace 8 90
Fat2 varies 5 0 45
Fruit 1/2 cup canned or 1/2 cup fresh or juice 0 0 80
1/2 cup dried 0 0 60
Starch/Bread varies trace 3 25
Vegetable 1/2 cup cooked, or 1 cup raw 0 2 25
1
2
Care must be taken to select fats that provide adequate linoleic and α-linolenic acids, such as those high in canola or
soybean oil.

TABLE 18-4. Pyruvate Carboxylase Deficiency Diet Guide
Name:______________________________________________________________
Date: __________/_________/_________
Mo Day Year
Birthdate: __________/_________/__________ Age: _______________________

Mo Day Year
Medical Food Amount Protein Fat Energy

(g) (g) (kcal)
ProViMin g
mL
mg
mg
mg
Skim milk cups
Add water to make ________________________ mL ________________ (fl oz)
Cereals: With Fruit
Desserts
Fruits/Juices
Meats
Vegetables
Total per day

Total per kg
Comments:
____________________________________________________
Nutritionist

TABLE 18-5. Pyruvate Carboxylase Deficiency Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

Length/ Weight Head ALA CIT LYS PRO Plasma NH3 Blood Citrate Blood Ferritin Albumn Hgb Fat ASP Citrate GLU Protein Energy B1
Height Circum Lactate Glucose (g/dL) ASPNH2 GLUNH2
(mo/d/yr) (cm) (kg) (cm) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (mmol/L) (mmol/L) (mg/dL) (ng/mL) (g/dL) (g) (%) (mg) (mg) (mg) (g) (kcal) (mg/day)
Pyruvate Carboxylase Deficiency 335
REFERENCES
1. Ahmad A, Kahler SG, Kishnani PS, et al: Treatment of pyruvate carboxylase deficiency with high doses of citrate
and aspartate. Am J Med Genet 1999;87:331-338.
2. Atkin BM, Buist NRM, Utter MF, et al: Pyruvate carboxylase deficiency and lactic acidosis in a retarded child
without Leigh's Disease. Pediatr Res 1979;13:109-116.
3. Atkin BM, Utter MF, Weinberg MG: Pyruvate carboxylase and phosphoenolpyruvate carboxykinase activity in
leukocytes and fibroblasts from a patient with pyruvate carboxylase deficiency. Pediatr Res 1979;13:38-43.
4. Baal MG, Gabreels FJM, Renier WO, et al: A patient with pyruvate carboxylase deficiency in the liver: Treatment
with aspartic acid and thiamine. Dev Med Child Neurol 1981;23:521-530.
5. Bartlett K, Ghneim HK, Stirk JH, et al: Pyruvate carboxylase deficiency. J Inher Metab Dis 1984;7:Suppl 1:74-78.
6. Besley GTN: First trimester diagnosis of pyruvate carboxylase deficiency. J Inher Metab Dis
1996;19 Suppl 1:69 (Abs).
7. Brunette MG, Delvin E, Hazel B, Scriver CR: Thiamine-responsive lactic acidosis in a patient with deficient low-Km
pyruvate carboxylase activity in liver. Pediatrics 1972;50:702-711.
8. Caruso U, Adami A, Bertini E, et al: Respiratory chain and pyruvate metabolism defects: Italian collaborative
survey on 72 patients. J Inher Metab Dis 1996;19:143-148.
9. Coude FX, Ogier H, Marsac C, et al: Secondary citrullinemia with hyperammonemia in four neonatal cases of
pyruvate carboxylase deficiency. Pediatrics 1981;68:914.
10. DeVivo DC, DiMauro S: Disorders of pyruvate metabolism, the citric acid cycle, and the respiratory chain.
In Fernandes J, et al (eds): Inborn Metabolic Diseases. Diagnosis and Treatment. New York: Springer Verlag,
1990, pp 127-157.
11. DeVivo DC, Haymond MW, Leckie MP, et al: The clinical and biochemical implications of pyruvate carboxylase
deficiency. J Clin Endocrinol Metab 1977;45:1281-1296.
12. Feldman GL, Wolf B: Letter to the Editor: Measurement of pyruvate carboxylase activity in amniotic fluid cells.
Pediatr Res 1979;14:153.
Washington DC: National Academy of Sciences, 1980 and 1989.
14. Greter J, Gustafsson J, Holme E: Pyruvate carboxylase deficiency with urea cycle impairment. Acta Paediatr
Scand 1985;74:982-986.
15. Gröbe H, Bassewitz DB, Dominick H-Chr, Pfeiffer RA: Subacute necrotizing encephalomyelopathy. Clinical,
ultrastructural, biochemical and therapeutic studies in an infant. Acta Paediatr Scand 1975;64:755-762.
16. Grover WD, Auerbach VH, Patel MS: Biochemical studies and therapy in subacute necrotizing
encephalomyelopathy (Leigh's Syndrome). J Pediatr 1972;81;39-44.
17. Hamilton J, Rae MD, Logan RW, Robinson PH: A case of benign pyruvate carboxylase deficiency with normal
development. J Inher Metab Dis 1996;19 (Suppl 1):68 (Abs).
18. Hansen TL, Christensen E, Brandt NJ: Studies on pyruvate carboxylase, pyruvate decarboxylase, and lipoamide
dehydrogenase in subacute necrotizing encephalomyelopathy. Acta Paediatr Scand 1982;71:263-267.
19. Haworth JC, Robinson BH, Perry TL: Lactic acidosis due to pyruvate carboxylase deficiency. J Inher Metab Dis
1981;4:57-58.
20. Hommes FA, Polman A, Reefrink JD: Leigh's encephalomyelopathy: An inborn error of gluconeogenesis. Arch Dis
Child 1968;43:423-426.
21. Kerr DS, Wexler ID, Zinn AB: Disorders of pyruvate metabolism and the tricarboxylic acid cycle. In Fernandes J, et
al (eds): Inborn Metabolic Diseases, ed 3. New York, Springer, 2000, pp 127-138.
1989;143:537-542.
1982.
24. Maesaka H, Komiya K, Misugi K, Tada K: Hyperalaninemia, hyperpyruvicemia and lactic acidosis due to pyruvate
carboxylase deficiency of the liver: Treatment with thiamine and lipoic acid. Eur J Pediatr 1976;122:159-168.
25. Marsac C, Augerseau CH, Feldman G, et al: Prenatal diagnosis of pyruvate carboxylase deficiency. Clin Chim Acta
1982;119:121-127.
1987;1:1-17.
27. Merinero B, Perez-Cerda C, Ugarte M: Investigation of enzyme defects in children with lactic acidosis. J Inher
Metab Dis 1992;15:696-706.
28. Oizumi J, Ng WG, Donnell GN: Pyruvate carboxylase defect: Metabolic studies on cultured skin fibroblasts. J Inher
Metab Dis 1986;9:120-128.
29. Oizumi J, Shaw KNF, Carter M, et al: Neonatal pyruvate carboxylase deficiency with renal tubular acidosis and
cystinuria. J Inher Metab Dis 1983;6:89-94.
30. Pollock MA, Cumberbatch M, Bennett MJ, et al: Pyruvate carboxylase deficiency in twins. J Inher Metab Dis
1986;9:29-30.
31. Przyrembel H: Therapy of mitochondrial disorders. J Inher Metab Dis 1987;10:129-146.
32. Robinson BH: Lactic acidemia: Disorders of pyruvate carboxylase, pyruvate dehydrogenase). In Scriver C, et al
(eds): The Metabolic and Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill Medical Publishing
Division, 2001, pp 2275-2296.
33. Robinson BH, Oei J, Sherwood WG, et al: The molecular basis for two different clinical presentations of classical
pyruvate carboxylase deficiency. Am J Hum Genet 1984;36:283-294.
34. Robinson BH, Sherwood WG: Lactic acidaemia. J Inher Metab Dis 1984;7 Suppl 1:69-73.
35. Saudubray JM, Marsac C, Charpentier C, et al: Neonatal congenital lactic acidosis with pyruvate carboxylase
deficiency in two siblings. Acta Paediatr Scand 1976;65:717-724.
1976.
37. Soldin SJ, Brugnara C, Hicks JM (eds): Pediatric Reference Ranges, ed 3. Washington, DC: AACC Press, 1999.
1989;143:828-832.
39. Stern HJ, Nayar R, DePalma L, Rifai N: Prolonged survival in pyruvate carboxyl's deficiency: Lack of correlation
with enzyme activity in cultured fibroblasts. Clin Biochem 1995;28:85-89.
40. Tada K, Takada G, Omura K, Itokawa Y: Congenital lactic acidosis due to pyruvate carboxylase deficiency:
Absence of an inhibitor of TPP-ATP phosphoryltransferase. Eur J Pediatr 1978;127:141-147.
41. Tang TT, Good TA, Dyken PR, et al: Pathogenesis of Leigh's encephalomyelopathy. J Pediatr 1972;81:189-190.
42. Tsuchiyama A, Dyanagi K, Hirano S, et al: A case of pyruvate carboxylase deficiency with later prenatal diagnosis
of an unaffected sibling. J Inher Metab Dis 1983;6:85-88.
43. Ullrich K, Schmidt H, van Teeffelen-Heithoff A: Glycogen storage disease type I and III and pyruvate carboxylase
deficiency: Results of long-term treatment with uncooked cornstarch. Acta Paediatr Scand 1988;77:531-536.
44. van Biervliet JPGM, Bruinvis L, van der Heiden C, et al: Report of a patient with severe, chronic lactic acidaemia
and pyruvate carboxylase deficiency. Dev Med Child Neurol 1977;19:392-401.
45. van Coster RN, Fernhoff PF, DeVivo DC: Pyruvate carboxylase deficiency: A benign variant with normal
development. Pediatr Res 1991;30:1-4.
46. Vidailhet M, Lefebvre E, Beley G, Marsac C: Neonatal lactic acidosis with pyruvate carboxylase inactivity J Inher
Metab Dis 1981;4:131-132.
1977;30:1269-1280.

PROTOCOL 19 — Fasting Chylomicronemia

I. Introduction
Lipoprotein lipase (LPL) is required for hydrolysis of triacylglycerols and their conversion to
intermediate-and low-density lipoproteins. Apolipoprotein C-II is required for activation of LPL (5, 12,
29).
LPL deficiency is transmitted as an autosomal recessive disorder and is characterized by fasting
chylomicronemia, abdominal pain, pancreatitis, eruptive xanthomas, and hepatosplenomegaly.
Symptoms of apolipoprotein C-II deficiency are the same as for LPL deficiency since LPL does not
function without apoprotein C-II. Some patients develop fasting chylomicronemia because they have a
LPL inhibitor in their plasma. LPL inhibitor appears to be inherited differently than LPL deficiency (5,
12, 21, 28).

LPL deficiency is not associated with atherosclerosis. However, recurring pancreatitis can be life
threatening. Restriction of dietary fat to 8% to 15% of energy is usually adequate to prevent
symptoms (5, 9, 17, 19, 22, 25).

A. The Defect
1. Fasting chylomicronemia may result from 1 of 3 defects (5):
a. Lipoprotein lipase deficiency (5).
b. Apolipoprotein C-II deficiency (4, 13).
c. Inhibitor of lipoprotein lipase (5).
1. Infants or children with any of the following clinical symptoms resulting from unknown causes
should be evaluated for chylomicronemia (5, 11, 14 18):
a. Abdominal pain presenting as colic.
b. Abdominal distention.
c. Hepatomegaly.
d. Splenomegaly.
e. Acute or chronic pancreatitis.
f. Eruptive xanthomas.
g. Lipemia retinalis.
h. "Milk" or "cream" layer on blood or plasma that is refrigerated overnight.
1. Differential diagnosis is required for genetic counseling.
2. See references 5, 17, and 29 for methods of diagnosis.

1. Restrict dietary fats to level that maintains fasting plasma triacylglycerol concentrations in
treatment range.

A. Fasting Plasma Triacylglycerol Concentrations
1. Maintain fasting plasma concentrations < 500 mg/dL in infants and < 750 mg/dL in children
and adults.
a. 5th and 95th percentiles in normal infants are 34 and 112 mg/dL
b. 5th and 95th percentiles in normal children and adults are 29 and 324 mg/dL (12, 17, 23,
25).
© 2001 Ross Products Division Fasting Chylomicronemia 343

B. Growth and Nutrition Status
1. Support normal growth rate in infants and children (3, 15) and maintain appropriate weight for
height in adults.
2 Maintain normal nutrition status.
C. Prevent Symptoms and Physical Manifestations of Chylomicronemia (5)
D. Prevent Fat-Soluble Vitamin Deficiency (24)

A. Energy
Warning: Inadequate energy intake will result in growth failure (15) in infants and
children and weight loss in adults.
B. Fat
a. Tolerance for fat varies depending on defect present (2, 6-9, 22, 24, 25) and is
determined by measuring fasting plasma triacylglycerol concentrations.
b. Supply 8 % to 15% of energy as fat (Table 19-1, p 344) (3, 7-9, 22, 24, 25).
1) Prescribe minimum of 3% of total energy as linoleic acid and 1% of total energy as
α-linolenic acid.
2) Addition of soy oil for infants and canola oil for children and adults may be required as
source of α-linolenic acid.
α-linolenic acid are inadequate.
C. Protein
1. Prescribe amount that supplies 15% to 20% of total energy for infants (Table 19-1, p 344).
D. Carbohydrate
E. Fluid
2. Requirements may be higher than recommended secondary to fever.
F. Fat-Soluble Vitamins (24)
1. Prescribe amounts that maintain normal plasma concentrations.
a. Plasma retinol should be maintained > 20 µg/dL.
b. Plasma 25-dihydroxyvitamin D should be maintained between 30 and 60 ng/mL.
c. Plasma α-tocopherol should be maintained > 0.6 mg/dL.
G. High-Dose Antioxidant Therapy (13)
1. Heaney, et al (13) used the following antioxidant therapy to prevent pancreatitis in three
patients with lipoprotein lipase deficiency.
Beta-carotene 9,000 IU/day
Methionine (not an antioxidant) 500 mg/day
Selenium 600 µg/day 1
Vitamin C 540 mg/day
Vitamin E 270 IU/day
Warning: THIS AMOUNT OF SELENIUM MAY CAUSE TOXIC SYMPTOMS IF GIVEN FOR A
PROLONGED TIME.
344 Fasting Chylomicronemia © 2001 Ross Products Division

A. Protein
1 Supply prescribed protein for neonates and infants with ProViMin ® until the 2nd birthday to
supply iron (Table 19-2, p 344).
2. Supply prescribed protein for children (> 2.0 years of age) and adults with lean meat, poultry
and fish; skim milk; and egg whites (Table 19-3, p 345). Fat in lean meat, poultry, and sea
foods must be counted as part of fat prescription.
B. Fat
1. Use soy or walnut oil to provide fat required for infant (Appendix 10, p A-9).
2. Use measured amounts of soy, walnut, or canola oil; beikost; or table foods to provide fat for
children and adults.
C. Energy
1. Calculate energy supplied by ProViMin, skim milk, other protein-containing foods, and fat.
(23 kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9), sugar (48 kcal/Tbsp),
beikost, or table foods containing little or no fat (Tables 19-2 and 19-3, pp 344 and 345).
a. Do not use honey for infants because it may contain botulinum toxin.
4. Add beikost or table foods after infant is 3 to 4 months old to provide variety in taste, color,
and texture (Table 19-2, p 344).
5. See Table 19-4, p 345, for types and amounts of foods that will supply infant's daily nutrient
needs.

2. Measure or weigh specified amounts of boiled, cooled water, ProViMin, fat, and carbohydrate
into clean containers.
4. Slowly pour specified amount of fat into blender and continue blending for no longer than 1 to
3 seconds.
5. Dissolve powdered carbohydrate in some of remaining water and pour into ProViMin and fat
mixture, mix well, add water to yield prescribed volume,
mixing because of nutrient loss. Shake well before feeding.
E. Diet Guide
1. Provide parents, caretakers, or patient with completed Diet Guide (Table 19-5, p 346, or 19-6,
p 347) with each diet change.

a. See Table 19-2, p 344 for composition of ProViMin and beikost, Table 19-3, p 345, for
Exchange Lists of foods for children and adults, Appendix 8, A-8, for composition of skim
milk, and Appendix 9, p A-9, for composition of Polycose.

not available.
b. If ProViMin mixture provides < 100% of RDIs for infants and < 75% for children and
supplements).
B. Osmolarity
b. Osmolarity per gram ProViMin powder is 2.74 mosm.
2. If osmolarity is > 450 mosm/L for infants, or is greater than tolerated by patient, increase
water content of prescribed medical food mixture and recalculate its osmolarity (16).
2. If concentration of prescribed food mixture prescribed is > 27 kcal/fl oz, estimate its potential
renal solute load.
recalculate.

A. Fat Tolerance
1. Initial.
a. Evaluate fasting plasma triacylglycerol concentrations weekly by quantitative methods
until fat intake as percentage of total daily energy maintains triacylglycerol concentration
in treatment range (18).
2. Ongoing.
a. After fat tolerance is determined, measure fasting plasma triacylglycerol concentrations
monthly until patient is 3 months of age, every 2 months to 1 year of age, and every
3 months thereafter, unless patient is noncompliant.
B. Protein Status
1. Evaluate plasma albumin concentration every 3 months until patient is 1 year old and 6
months thereafter (Appendix 17, p A-18, for standards).
normal range.
C. Iron Status

D. Growth Status
a. Measure monthly to 1 year and every 6 months thereafter. Plot measurements on NCHS
growth charts.
achieved.
E. Nutrient Intake
and 25, pp A-26 and A-27).
not available.
F. Clinical Summary
A. Example 1
Intakes from Table 19-1, p 344, and nutrient composition of ProViMin from Table 19-2, p 344, and
soy oil from Appendix 10, p A-9.
(g) (g) (kcal)
ProViMin 17.0 g 0 12.4 53
Soy oil 7 mL 6.3 0.0 56
Polycose Liquid 156 mL 0 0.0 312

Percentage of energy as fat 13.5%
is < 180 mosm.
Linoleic acid is 3.2 g or 6.8% of energy. α-Linolenic acid is 0.44 g or 0.9% of energy.

B. Example 2
Establish and fill prescription for 3-year-old child using Recommended Daily Nutrient Intakes from
Table 19-1, p 344, and nutrient contents from Table 19-3, p 345.
Energy 1,300 kcal
Fat 1,300 kcal x 0.15 = 195 kcal ÷ 9 = 22 g
Protein 23 g (minimum)
Fluid 1,400 mL
Measure Fat Protein Energy
(g) (g) (kcal)
Fat 4 exchanges1 20 0 180
Fruits 6 exchanges 0 0 420
Milk, skim 3 cups trace 24 270
Starch/Breads 4 exchanges trace 12 320
Vegetables 4 exchanges 0 8 100
Total per day 23 51 1,396

1
Use 1 Tbsp of canola oil as 3 exchanges

A. Rationale
protein (29).
2. Well-nourished patients with chylomicronemia respond to infection and trauma as do normal
persons.
Jell-O ®, Polycose powder or liquid (Appendix 9, p A-9) added to fruit juices or Pedialyte if
tolerated, and caffeine-free soft drinks (not diet drinks).
1) Add 1/3 cup Polycose powder to Pedialyte liquid to yield 8 fl oz.
possible.
Warning: Intravenous lipid solutions supplying > 15% of energy are contraindicated in
treatment of chylomicronemias.
XII. Contraindicated Drugs (22)

A. Alcohol
B. ß-Adrenergic Blocking Agents
C. Diuretics
D. Estrogens
E. Isoretinoin

Chylomicronemia
Age Nutrient
1
(% of energy) (% of energy) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 15 - 20 8 - 15 120 (145 - 95) 150 - 125
3 to < 6 mo 15 - 20 8 - 15 115 (145 - 95) 160 - 130
6 to < 9 mo 15 - 20 8 - 15 110 (135 - 80) 145 - 125
9 to < 12 mo 15 - 20 8 - 15 105 (135 - 80) 135 - 120
(g/day) (% of energy) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 23 - 30 8 - 15 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr 30 - 37 8 - 15 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr 37 - 44 8 - 15 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr 46 - 53 8 - 15 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr 46 - 53 8 - 15 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr 53 - 60 8 - 15 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr 45 - 52 8 - 15 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr 59 - 66 8 - 15 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr 63 - 69 8 - 15 2,900 (2000 - 3300) 2,000 - 3,300
1
2
Modified from reference 1. Under normal circumstances, offer a minimum of 1.5 mL fluid to neonates and 1.0 mL to
TABLE 19-2. Approximate Macronutrient Contents of Gerber ® Baby Foods (Beikost) and ProViMin ®1

(g) (g) (kcal)
2
Cereals, with fruit, 2nd and 3rd Foods, jarred 1 Tbsp < 0.10 0.16 10
2
Desserts: 2nd and 3rd Foods 1 Tbsp 0.04 0.11 11
2
Fruits, 1st, 2nd and 3rd Foods 1 Tbsp 0.00 0.09 10
Fruit, juice 1 fl oz 0.00 0.07 16
2
Meats, 2nd and 3rd Foods 1 Tbsp 0.67 1.58 15
ProViMin 100 g 2.00 73.00 312
2
Vegetables: 1st, 2nd and 3rd Foods 1 Tbsp 0.12 0.20 6
1
2

TABLE 19-3. Exchange Lists for Nutrition Support of Children and Adults With Fasting Chylomicronemias1
Food List Amount Fat Protein Energy

(g) (g) (kcal)
2
Milk, skim 1 cup trace 8 90
Fat 3 varies 5 0 45
Fruit 1/2 cup canned 0 0 80
1/2 cup fresh or juice, or 1/2 cup dried 0 0 60
Vegetable 1/2 cup cooked or 1 cup raw 0 2 25
1
2
From reference 20.
3
soybean oil.
TABLE 19-4. Types and Amounts of Infant Foods That Will Supply the Daily Nutrient Needs of Infants With
Chylomicronemia
Food Amount of Food Required by Age

0 to < 3 months 3 to < 6 months 6 to < 9 months 9 to < 12 months
1
ProViMin, 20 kcal/oz, mL 175 - 150/kg 160 - 130/kg 130 - 110/kg 110 - 90/kg
2
Infant cereals, Tbsp None 0.5 - 1/kg 1/kg 1/kg
2
Fruits, puréed, Tbsp None 1/kg 1/kg 1/kg
2
Meats, 2nd & 3rd Foods, Tbsp None None 1/kg 1/kg
2
Vegetables, puréed, Tbsp None 1/kg 1/kg 1/kg
1
Formula must be sufficient to supply energy normally supplied by fat.
2
Introduce teaspoon-size portions after infant is 3 to 4 months of age, or when tongue thrust disappears. Allow 3 to
5 days to elapse between addition of each new food to determine if infant is allergic to food. Gradually increase
portion sizes until recommended amounts are consumed.

TABLE 19-5. Diet Guide for Infants With Fasting Chylomicronemia
Date: ____________/___________/__________
Mo Day Year
Name:_____________________________________________________________________
Birthdate: ____________/___________/__________ Age: ___________________________

Mo Day Year
Length: ____________________________ (cm/in) Weight: __________________ (kg/lb)
Fat Protein Energy

Medical Food Mixture Amount (g) (g) (kcal)
ProViMin g
g/Tbsp
mL
mL
mL
Add water to make mL (fl oz)
Baby Food Amount
Cereals Tbsp
Desserts Tbsp
Fruits/Juices Tbsp/fl oz
Meats, 2nd & 3rd Foods Tbsp
Vegetables Tbsp
Total per day

Total per kg
Comments:
______________________________________________
Nutritionist

TABLE 19-6. Diet Guide for Children and Adults With Fasting Chylomicronemia
Date: _____________/______________/______________
Mo Day Year
Name:_____________________________________________________________________
Date: _____________/______________/______________ Age: ______________________

Mo Day Year
Length: __________________ (cm/in) Weight: _______________________ (kg/lb)
Food List Exchanges Fat Protein Energy
(g) (g) (kcal)
Meat, lean
Milk, skim
Fat
Fruit
Starch/Bread
Vegetables
Total per day
Comments:
______________________________________________
Nutritionist

TABLE 19-7. Fasting Chylomicronemia Clinical Summary Sheet
348 Fasting Chylomicronemia
Date of Birth: __________/__________/__________

Mo Day Year

Length/ Weight Head TAG1 Ferritin Albumin Hgb Fat Linoleic α-Linolenic Acid Protein Energy
Height Circum (g/dL) Acid
(mo/d/yr) (cm) (kg) (cm) (mg/dL) (ng/mL) (g/dL) (g) (% kcal) (g) (g) (g) (kcal)
1
Triacylglycerols
REFERENCES
1996.
2. Berger GMB: An incomplete form of familial lipoprotein lipase deficiency presenting with Type I
hyperlipoproteinemia. Am J Clin Pathol 1987;88:369-373.
3. Black DM, Sprecker DL: Dietary treatment and growth of hyperchylomicronemic children severely restricted in
dietary fat. Am J Dis Child 1993;147:60-62.
4. Brechenridge WC, Alaupovic P, Cox DW, Little JA: Apolipoprotein and lipoprotein concentrations in familial
apolipoprotein C-II deficiency. Atheroscler 1982;44:233-235.
5. Brunzell JD, Deeb SS: Familial lipoprotein lipase deficiency, apoC-II deficiency and hepatic lipase deficiency. In
Scriver CR, et al (eds): The Metabolic and Molecular Bases of Inherited Disease, ed 8. New York: McGraw-Hill
Medical Publishing Division, 2001, pp 2789-2816.
6. Brunzell JD, Chait A, Nikkila EA, et al: Heterogeneity of primary lipoprotein lipase deficiency. Metabolism
1980;29:624-628.
7. Bucher H, Rampini S, James RW, et al: Marked changes of lipid levels during puberty in a patient with lipoprotein
lipase deficiency. Eur J Pediatr 1997;156:121-125.
8. Deckelbaum RJ, Dupont C, LeTarte J, Pencharz P: Primary hypertriglyceridemia in childhood. Am J Dis Child
1983;137:396-398.
9. Feoli-Fonseca JC, Levy E, Godard M, Lambert M: Familial lipoprotein lipase deficiency in infancy: Clinical,
biochemical, and molecular study. J Pediatr 1998;133:417-423.
11. Gasbarrini G, Mingrone G, Greco AV, Castagneto M: An 18-year old woman with familial chylomicronaemia who
would not stick to diet. Lancet 1996;348:794.
12. Havel RJ, Kane JP: Introduction: Structure and metabolism of plasma lipoproteins. In Scriver CR, et al (eds): The
2001, pp 2705-2716.
13. Heaney AP, Sharer N, Rameh B, et al: Prevention of recurrent pancreatitis in familial lipoprotein lipase deficiency
with high-dose antioxidant therapy. J Clin Endocrinol Metab 1999;84:1203-1205.
14. Levy RI, Rifkind BM: Diagnosis and management of hyperlipoproteinemia in infants and children. Am J Cardiol
1973;31:547-556.
1989;143:537-542.
1982.
17. Nyhan WL, Ozand PT: Lipoprotein lipase deficiency type I hyperlipoproteinemia. In Atlas of Metabolic Diseases,
New York: Chapman and Hall Medical 1998, pp 515-522.
18. Ohno M, Ishibashi S, Nakao K, et al: A neonatal case of apolipoprotein C-II deficiency. Eur J Pediatr
1989;148:550-552.
19. Ohta T, Nakamura R, Ikeda Y, et al: Follow up study on children with dyslipidaemia detected by mass screening at
18 months of age: Effect of 12 months dietary treatment. Eur J Pediatr 1993;152:939-943.
21. Rane HS, Garu R, Lahari KR, Desai AJ: Primary hyperlipoproteinemia type I. Indian J Pediatr 1984;51:243-245.
22. Santamarina-Fojo S: The familial chylomicronemia syndrome: Endocrinol Metab Clin NA 1998;27:551-567.
23. Schaefer EJ, Levy RI: Pathogenesis and management of lipoprotein disorders. N Engl J Med 1985;312:1300-1310.
24. Shankar KN, Bara HS, Shetty J, Joshi MK: Lipoprotein lipase deficiency. J Postgrad Med 1997;43:81-82.
25. Siafakas CG, Brown MR, Miller TL: Neonatal pancreatitis associated with familial lipoprotein lipase deficiency.
J Pediatr Gastroenterol Nutr 1999;29:95-98.
1976.
27. Taskinen MR: Hypolipoproteinemia and lipoprotein lipase deficiency. In Fernandes J, et al (eds): Inborn Metabolic
Diseases: Diagnosis and Treatment. New York: Springer-Verlag, 1990, pp 381-394.
1977;30:1269-1280.

PROTOCOL 20 — Mitochondrial Fatty Acid Oxidation Defects

I. Introduction
Fatty acids are a primary metabolic fuel for the body when fasting is prolonged and a direct source of
energy for heart and skeletal muscle. Ketones such as acetoacetate and ß-hydroxybutyrate, obtained
during hepatic fat metabolism, are an important energy source for the brain in particular, as well as
other tissues. Infants and young children may have problems adapting to fasting due to their high
basal energy needs required to maintain body temperature; the high rate of brain metabolism; and the
low activity of several enzymes involved in energy production (42).
During fasting, fatty acids are released from adipocytes and carried to other tissues by lipoproteins or
albumin. Fatty acids with > 10 carbons are activated to-CoA esters in the cytosol. These acyl-CoA
compounds are carried to the mitochondria by carnitine palmitoyl transferase types I and II (CPT I
and II). Fatty acids with < 10 carbons do not require CPT I and II to enter the mitochondria, where they
are activated to-CoA esters (42).
In the mitochondria, fatty acids are degraded by the sequential removal of 2-carbon fragments as
acetyl-CoA (Figure R). Four carbon chain length-specific enzymes are required: an acyl-CoA
dehydrogenase, an enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and a 3-ketoacyl-CoA
thiolase (Figure R). In the liver, most of the acetyl-CoA is used for ketone body synthesis (42).
Deficiencies of very long-chain-, long-chain-, medium-chain-, short-chain-, 3-hydroxy-, and short-
chain-hydroxyacyl-CoA dehydrogenases and mitochondrial trifunctional protein (51, 54) have been
reported. Medium-chain-acyl-CoA dehydrogenase deficiency (MCADD) was found to occur in about
1/8,900 live births in Pennsylvania (63). Similar initial symptoms are found in all the dehydrogenase
deficiencies. Some patients may develop symptoms as neonates. Symptoms are often induced by
fasting or an infection with vomiting or diarrhea. Lethargy, muscle weakness, seizures, coma, and
death may occur. Fatty infiltration of organs is often found on autopsy (37, 42).
Substrate Chemical structure Enzyme
Acyl -CoA R-CH 2-CH 2-CH 2-CO -S-CoA
FAD
Acyl - CoA dehydrogenase

FADH 2
Enoyl -CoA R-CH 2-CH -CH -CO -S-CoA

H2O
Enoyl -CoA hydratase
3-Hydroxyacyl -CoA R-CH 2-CHOH -CH 2-CO -SCoA

NAD 3-Hydroxyacyl -CoA dehydrogenase
NADH 2
3-Ketoacyl -CoA R-CH2 -CO -CH2 -CO -S-CoA
3-Ketoacyl -CoA thiolase
Acetyl -CoA CH3 -CO -S-CoA Site of possible enzyme defect.
Figure R. Mitochondrial ß-oxidation (modified from reference 42)

Development of pigmentary retinopathy or peripheral neuropathy is specifically associated with long-
chain-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency (3, 19, 37, 46). Some mothers who are
heterozygous for mitochondrial fatty acid oxidation (FAO) defects develop acute fatty liver of
pregnancy during the 3rd trimester of pregnancy (49, 60).
© 2001 Ross Products Division Mitochondrial FAO Defects 355

Variable outcomes of nutrition support have been reported in infants and children with long-chain-FAO
defects. As with most metabolic disorders, severity of the enzyme defect, time of diagnosis, and long-
term metabolic control influence the long-term outcome for these patients. Although fatal hypoketotic
hypoglycemic episodes may occur in children with any long-chain-FAO defect, long-term intensive
nutrition support has been associated with positive outcomes in several reports (14, 23, 32, 39, 52,
61). A diet restricted in long-chain-fatty acids but supplemented with fractionated coconut oil (MCT) is
the most effective treatment for infants and children affected with disorders of long-chain-FAO.
Reported benefits include decreased frequency of metabolic crises, improved muscle tone, sustained
physical growth, and developmental gains.
Of 120 patients with MCADD reported in the United States, 23 expired; of the 97 surviving patients,
16% had muscle weakness, 14% had failure to thrive, 40% had developmental delay, 22% had
speech disabilities, 11% had attention deficit disorder, and 9% had cerebral palsy. All children were
told to avoid fasting, 70 received supplemental L-carnitine, 60 received a low-fat diet, 2 were given
supplemental glycine (GLY), and 1 received supplemental riboflavin (22).

A. The Defect (24, 42, 46, 52-54, 62)
1. Disorders of mitochondrial FAO may result from 1 of several defects:
a. Very-long-chain-acyl-CoA dehydrogenase deficiency.
b. Long-chain-acyl-CoA dehydrogenase deficiency.
c. Long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency.
d. Medium-chain-acyl-CoA dehydrogenase deficiency.
e. Short-chain-acyl-CoA dehydrogenase deficiency.
f. Short-chain-hydroxyacyl-CoA dehydrogenase deficiency.
g. Mitochondrial trifunctional protein deficiency.
B. Differential Diagnosis (44, 58, 59)
1. Infants or children who, on fasting, have episodes of arrhythmias (4), lethargy, vomiting,
hepatomegaly, or Reye-like syndrome, seizures, cardiomyopathy, peripheral neuropathy,
pigmentary retinopathy, or coma associated with any of the following laboratory findings
should have a diagnostic work-up for FAO defect:
a. Hypoketotic hypoglycemia.
b. Minimal metabolic acidosis.
c. Elevated blood urea nitrogen (BUN) concentration.
d. Elevated blood ammonia concentration.
e. Elevated plasma urate concentration (11).
f. Elevated concentration of transaminases.
g. Myoglobinuria (13).
h. Plasma carnitine deficiency.
i. Dicarboxyluria.
j. Rhabdomyolysis (43).
2. Siblings of children who have died with sudden infant death syndrome (SIDS) or Reye's
syndrome should be evaluated for FAO defect (11, 21, 35, 42).
3. See references 5, 9, 17-19, 28, 31, 42, 51, and 57 for methods of diagnosis to determine
which defect is present.

1. Restrict type and amount of dietary fat to level tolerated by patient and appropriate to
diagnosis to decrease production of abnormal metabolites (6, 16).
B. Supply "Conditionally Essential" Nutrients
1. Supplement L-carnitine to maintain plasma free carnitine in normal range (≥ 30 µmol/L).
C. Provide Alternate Pathway to Decrease Accumulated Toxic Precursors

1. Supplement GLY to enhance urinary loss of toxic acyl compounds as nontoxic
acylglycine (41).
356 Mitochondrial FAO Defects © 2001 Ross Products Division

D. Stabilize Altered Enzyme Proteins
1. Supplement oral riboflavin in pharmacologic amounts (12, 26).

A. Blood Glucose and Plasma Carnitine Concentrations
1. Maintain normal blood glucose concentrations.
2. Maintain normal plasma free carnitine ≥ 30 µmol/L (26, 45, 56).
3. Prevent accumulation of abnormal metabolites.
1. Support normal growth rate in infants and children, and maintain appropriate weight for height
in adults.
2. Prevent EFA deficiency.
b. Avoid prolonged fasting
5. Maintain adequate hydration
6. Avoid lipid storage in heart, liver and muscles (22, 45).

A. Energy
Warning: Inadequate energy intake will result in growth failure in infants and children,
weight loss in adults, and can adversely affect metabolic control if catabolism
of fat stores occurs (27).
B Protein
1. Prescribe amount that supplies 10-12% of total energy (Table 20-1, p 359).
C. Fat (44)
1. Prescribe amount of total fat that promotes goals of nutrition support (10, 16).
a. Very-long chain and long-chain-FAO defects:
1) Prescribe ~30% of energy as fat.
2) About 50% of fat energy should be derived from MCT and remainder from fats that
supply linoleic and α-linolenic acids (20, 34).
3) Docosahexaenoic acid may be essential for the patient with long-chain-3-hydroxyacyl-
CoA dehydrogenase deficiency.
i. Harding, et al (20) suggest 65 mg/day for children < 20 kg and 130 mg/day for
children > 20 kg.
b. Medium- and short-chain-FAO defects:
1) Provide 15-25% of total daily energy as fat (7, 33).
c. Prescribe 3% of total energy as linoleic acid and 1.0% as α-linolenic acid.
Warning: EFA deficiency may occur if intakes of linoleic acid and α-linolenic acid are
inadequate. Symptoms include dermal scaliness and increased skin
permeability, reduced growth rate, renal abnormalities, increased erythrocyte
fragility, increased susceptibility to infections, and decreased rate of
development (26, 40, 50).
D. Carbohydrate

E. Fluid
F. L-Carnitine
1. Prescribe amount that maintains normal plasma free carnitine concentration > 30 µmol/L.
2. Amounts of 50 to 150 mg/kg have been suggested (41, 46).
3. Efficacy of carnitine supplementation in treatment of FAO defects is debated but use is almost
standard therapy.
G. Glycine
1. Supplement diet with 100 to 200 mg/kg/day (41).
H. Riboflavin
1. Supplement diet with 100 to 200 mg/day, if beneficial (12, 26).
I. Fasting
1. Instruct parents, patient, or caretakers to prevent infants from fasting > 4 hours, children
> 6 hours, and adults > 8 hours.
2. Raw cornstarch (1.75-2.5 g/kg) helps prevent hypoglycemia (8).
Warning: Increased frequency of feeding, tube feedings, and IV glucose may be
necessary if patient is febrile, has diarrhea, or is vomiting.

A. Protein
1. Calculate grams of protein required to provide 10% to 12% of energy prescription.
2. Determine amount of protein provided by ProViMin, (Table 20-2, p 359), beikost, table foods
(Tables 20-2 and 20-3, pp 359 and 360), or skim milk (Appendix 8, p A-7) required to fill
protein prescription.
Warning: Do not use skim milk before patient is 2 years old.
B. Fat
1. Very-long-chain and long-chain-FAO defects:
a. Calculate grams of fat required to provide ∼30% of energy prescription.
1) Supply about 50% of fat energy with MCT oil (Appendix 26, p A-28).
i. MCT oil contains 8.2 kcal/g, 114.8 kcal/Tbsp, and 7.6 kcal/mL.
Warning: Administer MCT oil ONLY if defect in long-chain-FAO is confirmed since
addition of MCT oil is harmful to individuals with medium- or short-chain-FAO
defects.
b. If fat sources fail to supply 3% of energy as linoleic acid and 1% as α-linolenic acid, add
adequate amount of appropriate vegetable oil to supply (Appendix 10, p A-9).
c. Amount of MCT oil will need to be decreased if sources of EFAs increase dietary fat to
> 30% of energy.
d. Order docosahexaenoic acid from Martek Biosciences Corp, Columbia, MD, USA.
2. Medium- and short-chain-FAO defects:
a. Calculate grams of fat required to provide 15% to 25% of energy prescription.
b. Determine amount of vegetable oil (Appendix 10, p A-9), beikost, or table foods
(Tables 20-2 and 20-3, pp 359 and 360) required to fill fat prescription.
c. Use fat source that supplies adequate linoleic acid and α-linolenic acid.
C. Energy
1. Add energy supplied by beikost or table foods to those required to supply fat and to those
supplied by ProViMin, skim milk, carbohydrate, or other protein-containing foods.

3. Supply any remaining prescribed energy with Polycose ® Glucose Polymers powder
(23 kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9), sugar (48 kcal/Tbsp), or
puréed or table foods containing little or no fat (Tables 20-2 and 20-4, pp 359 and 360).
4. Add beikost or table foods after infant is 3 to 4 months old or is developmentally ready to
provide variety in taste, color, and texture (Table 20-2, p 359).
5. If additional carbohydrate is needed, see Table 20-4, p 360.

1. Add liquid L-carnitine to ProViMin medical food mixture.
E. Glycine (Appendix 26, p A-28)

1. Weigh GLY on scale that reads in grams.
2. Add sufficient boiled, cooled water to yield 100 mg/mL. (eg, 10 g GLY to yield 100 mL).
3. Store in refrigerator for 1 week, if not frozen.
4. Measure into medical food mixture with disposable syringe.
F. Riboflavin (Appendix 26, p A-28)

1. Have parents or patients finely crush number of tablets required to supply prescribed
milligrams of riboflavin if patient cannot swallow tablets.
2. Mix with medical food mixture.
3. Give 25 to 30 mg with each feed. Additional will not be absorbed. A greater amount is
absorbed when given with food than when fasting.
G. Fluid and Mixing Instructions for ProViMin

1. Boil bottles, nipples, rings, and mixing utensils for 5 minutes and cool. Boil more water for
5 minutes, then cool to room temperature.
2. Measure or weigh specified boiled, cooled water, ProViMin, fat, carbohydrate, L-carnitine,
GLY, and riboflavin into clean containers.
3. Pour about 1/2 specified volume of boiled, cooled water into clean blender. Running blender
at slow speed, gradually add ProViMin and fat and blend for at least 15 seconds.
4. Dissolve powdered carbohydrate in part of the water and pour into blended ProViMin and
infant formula mixture, add boiled, cooled water to yield final prescribed volume, mix well, and
pour into opaque sterilized nursing bottles or cups. Prepared formula not used immediately
should be refrigerated and used within 24 hours. Shake well before feeding.
7. Store unopened cans at room temperature. Cover opened can of ProViMin and store in dry
place (not in refrigerator). Use within 1 month after opening.
8. Notify parents or caretakers when they may discontinue use of aseptic technique in making
formula.
F. Diet Guide
each diet change.
Warning: Never permit patient to fast > 4 hours if infant, > 6 hours if child, or > 8 hours
if adult; shorten fasting time if patient is febrile, has diarrhea, or is vomiting.

a. See Table 20-2, p 359, for composition of ProViMin and Appendix 8, A-8, for skim milk.

vitamins (Table 6-4, p 118, and Appendices 13 and 14, pp A-14 to A-15).
not available.
b. If ProViMin mixture provides < 100% of RDIs for infants and < 75% for children,
supplements).
B. Osmolarity
b. Osmolarity per gram ProViMin powder is 2.74 mosm.
adults (30, 48), or is greater than tolerated by patient, increase water content of prescribed
renal solute load.
recalculate.

A. Quantitative Urine Organic Acids
1. Dicarboxylic aciduria may be detected in children with poorly controlled fat intake.
a. Fatty acids, either intact or partially oxidized, may undergo peroxisomal oxidation to
produce enzyme defect-specific dicarboxylic acids (36, 42).
b. Decrease in production of these metabolites will be seen with good dietary control.
c. Analyze urine organic acids every 2 to 3 months during 1st year and every 6-months
thereafter.
2. MCT supplementation is associated with increased urinary excretion of sebacic and suberic
acids (60).
B. Essential Fatty Acids
1. Low concentrations of docosahexaenoic (< 20 µg/mL), linoleic or α-linolenic acids in fasting or
preprandial plasma sample and triene to tetraene ratio > 0.03 are indicators of EFA deficiency
(20, 25).
2. With adequate EFA intake, plasma linoleic and α-linolenic acid concentrations will be within
normal limits and triene to tetraene ratio will be normal (0.02 ± 0.01).
a. Triene to tetraene ratio is considered more sensitive measure of deficiency than plasma
EFA concentration (25).
3. Evaluate EFA profile monthly for 1 year or when first establishing diet treatment.
4. If plasma linoleic or α-linolenic acid concentration is low or if triene to tetraene ratio is
elevated:
a. Increase linoleic or α-linolenic acid intake by 5% and reevaluate in 1 month.
b. If concentrations continue to be abnormal, repeat above until value is in normal range.
c. Correction in intake may require changing type of EFA oil source (Appendix 10, p A-9).
5. Decrease frequency of monitoring to every 3 months for older patients when diet treatment is
established and plasma EFA concentrations and triene/tetraene ratio are in normal range.

C. Plasma Carnitine Concentrations
1. Measure plasma free and total carnitine monthly until patient is 6 months of age; every 3 to
6 months thereafter.
2. If either free or total carnitine concentration is below normal:
a. Increase prescribed L-carnitine by 5% and reevaluate plasma concentrations after
1 month.
b. If either concentration continues below normal, repeat above process until value is in
normal range.
3. Plasma acylcarnitine concentrations are useful for monitoring (1).
D. Protein Status
1. Evaluate plasma albumin concentration every 3 months until patient is 1 year old, thereafter
measure twice yearly (Appendix 17, p A-18, for standards).
concentration after 1 month.
normal range.
E. Iron Status
F. Growth Status
a. Measure monthly to 1 year, every 3 months to 4 years, and twice yearly thereafter. Plot
achieved.
G. Nutrient Intake
and 25, pp A-26 and A-27).
not available.
H. Clinical Summary

A. Establish and fill prescription for 2 month-old infant weighing 5.2 kg who has LCHAD deficiency
using Recommended Daily Nutrient Intakes from Table 20-1, p 359, and nutrient contents from
Table 20-2, p 359, and Appendix 9, p A-9.
Fat 624 kcal x 0.30 = 187 kcal ÷9 = 20.8 g
Docosahexaenoic acid 65 mg x 5.2 kg = 338 mg
Linoleic acid 624 kcal x 0.03 = 18.7 kcal ÷9 = 2.1 g
α-Linolenic acid 624 kcal x 0.01 = 6.2 kcal ÷9 = 0.69 g
MCT oil 187 kcal x 0.50 = 93.5 kcal ÷ 8.2 = 11.4 g
Protein 624 kcal x 0.12 = 74.9 kcal ÷4 = 18.7 g
Fluid 145 mL/kg x 5.2 kg = 754 mL (25 oz)
Medical Food Mixture Measure Fat Linoleic α-Linolenic MCT Protein Energy
Acid Acid
(g) (g) (g) (g) (g) (kcal)
ProViMin 25.6 g 0.37 0.00 0.00 0.37 18.7 80
Soy oil 10.4 mL 9.40 4.78 0.73 0.00 0.0 84
Polycose Powder 96 g 0.0 0.00 0.00 0.00 0.0 365
MCT oil 12.3 mL 11.30 0 00 0.00 11.30 0.0 94
Total per day 21.07 4.78 0.73 11.67 18.7 623

Percentage of energy 29 6.90 1.05 15 11.98
is < 200 mosm.
B. Example 2
Establish and fill prescription for newborn weighing 3.5 kg who has MCADD using Recommended
Daily Nutrient Intakes from Table 20-1, p 359, and nutrient content from Table 20-2, p 359, and
Appendix 9, p A-9.
Glycine 100 mg x 3.5 kg = 350 mg
Riboflavin 200 mg = 200 mg

(g) (g) (kcal)
ProViMin 16.9 g 0.2 12.4 53
Glycine 350 mg 0.00 0.00 0.0
Soy oil 13 mL 11.7 0.0 103
Polycose Liquid 132 mL 0.0 0.0 264

Percentage of energy 25%
is < 170 mosm.

A. Rationale
protein (55).
2. Well-nourished patients with FAO defects respond to infection and trauma as do normal
persons
Jell-O ®, Polycose powder or liquid (Appendix 9, p A-9) added to fruit juices or Pedialyte if
tolerated, and caffeine-free soft drinks (not diet drinks).
1) Add 1/3 cup Polycose powder to Pedialyte liquid to yield 8 fl oz.
possible.
c. Feed Polycose solution (5-7 g/kg of carbohydrate) or carbohydrate-containing foods every
2 to 3 hours.
1) If unable to feed every 2 to 3 hours, administer solution of raw cornstarch (2 to 3 g/kg)
(1:2 ratio cornstarch to fluid) to children older than 9 months.
d. Administer 10% glucose solution intravenously if oral intake cannot be maintained.
3. Decrease intake of fatty acids.
a. Decrease fat content of diet or medical food mixture.
1) Increase Polycose in medical food mixture.
2) Remove oil prescribed for EFAs.
3) Remove MCT oil if not tolerated.
a. Add uncooked cornstarch, 2 to 3 g/kg/day, to any liquids and feed every 2 to 3 hours.
5. Prevent accumulation of toxic fatty acyl groups.
a. Add liquid L-carnitine to Pedialyte.
Warning: Intravenous administration of lipids is contraindicated.

TABLE 20-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With a
Mitochondrial FAO Defect
Age Nutrient
1
(% of energy) (kcal/kg) (mL/kg)
Infants
0 to < 3 mo 10 - 12 120 (145 - 95) 150 - 125
3 to < 6 mo 10 - 12 115 (145 - 95) 160 - 130
6 to < 9 mo 10 - 12 110 (135 - 80) 145 - 125
9 to < 12 mo 10 - 12 105 (135 - 80) 135 - 120
Girls and Boys
1 to < 4 yr ≥ 23 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr ≥ 30 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr ≥ 34 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr ≥ 46 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr ≥ 46 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr ≥ 50 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr ≥ 45 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr ≥ 59 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr ≥ 63 2,900 (2000 - 3300) 2,000 - 3,300
1
From reference 15.
2
From reference 2. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to children
and adults for each kcal ingested.
TABLE 20-2. Average Nutrient Contents of Gerber ® Baby Foods (Beikost), ProViMin ®, and MCT Oil1

(g) (g) (kcal)
Cereals, with fruit, 2nd ® and 3rd Foods ®, 1 Tbsp2 0.07 0.16 10
jarred
2
Desserts: 2nd and 3rd Foods 1 Tbsp 0.04 0.10 12
Fruits, 1st ®, 2nd ® and 3rd Foods ® 1 Tbsp2 0.00 0.19 10
Juices 1 fl oz 0.00 0.07 16
3
MCT oil 100 mL 93.30 0.00 765
2
Meats, 2nd ® and 3rd Foods ® 1 Tbsp 0.67 1.58 14
ProViMin 100 g 2.00 73.00 312
Vegetables: 1st ®, 2nd ® and 3rd Foods ® 1 Tbsp2 0.04 0.19 6
1
2
3
MCT oil contains 8.2 kcal/g fat.

TABLE 20-3. Exchange Lists for Nutrition Support of Children and Adults With Mitochondrial FAO Defects 1

(g) (g) (kcal)
Meat, lean 1 oz 3.0 7 55
Meat, very lean 1 oz 1.0 7 35
2
Milk, skim 1 cup 0.5 8 90
Fat 3 varies 5.0 0 45
Fruit 1/2 cup canned or 1/2 cup fresh or juice 0.0 0 60
1/2 cup dried 0.0 0 80
Vegetable 1/2 cup cooked, or 1 cup raw 0.5 2 25
1
2
From reference 38.
3
soybean oil.
TABLE 20-4. Fat-Free Foods to Help Supply Energy in Low-Fat Diets
Foods/Supplement Measure Energy

(kcal)
Carbonated beverages 4 fl oz 60
Corn syrup 1 Tbsp 57
Fruit and juice drinks 4 fl oz 60
Hard candy 3 pieces, approx 60
Jam, jelly 1 Tbsp 50
Jell-O ® 1/4 cup, prepared 65
Polycose ® Glucose Polymers, liquid 1 fl oz 59
Polycose ® Glucose Polymers, powder 2 Tbsp 45
Popsicles ®, frozen juice bars 1/2 cup 50
Slush Drinks (ie, Mr. Misty ®) 3 fl oz 60
Syrup 1 Tbsp 55

TABLE 20-5. Mitochondrial FAO Defects Diet Guide
Name:
Date: __________/_________/_________ Diagnosis:

Mo Day Year
Birthdate: __________/_________/__________ Age:

Mo Day Year
Length/Height: ____________________ (cm/in) Weight: (kg/lb)
Medical Food Amount Fat Protein Energy

(g) (g) (kcal)
ProViMin g
L-carnitine mg
Glycine mg
Riboflavin mg
Skim milk cups
Add water to make

_______________ mL/fl oz

Cereals: With Fruit

Desserts, low fat
Fruits/Juices
Meats, lean
Vegetables
Total per day
Total per kg
Comments:
____________________________________________________
Nutritionist

TABLE 20-6. Mitochondrial FAO Defects Clinical Summary Sheet
362 Mitochondrial FAO Defects
Date of Birth: __________/__________/__________ Diagnosis:

Mo Day Year

Length/ Weight Head Organic Plasma Carnitine Triene/ Blood Ferritin Albumin Hgb Fat Linoleic Acid α-Linolenic L-Carn Protein Energy
Height Circum acids Tetraene Glucose Acid
Total Free Ratio
(mo/d/yr) (cm) (kg) (cm) (µmol/L) (µmol/L) (µmol/L) (mg/dL) (ng/mL) (g/dL) (g/dL) (g) (%) (g) (%) (g) (%) (mg) (g) (kcal)
REFERENCES
1. Abdenur JE, Chamoles NA, Specola N, et al: MCAD deficiency. Acylcarnitines (AC) by tandem mass spectrometry
(MS-MS) are useful to monitor dietary treatment. Adv Exp Med Biol 1999;466:353-363.
1996.
3. Bertini E, Dionisi-Vici C, Garavaglia AB, et al: Peripheral sensory-motor polyneuropathy, pigmentary retinopathy,
and fatal cardiomyopathy in long-chain-3-hydroxy-acyl-CoA dehydrogenase deficiency. Eur J Pediatr
1992;151;121-126.
4. Bonnet D, Martin D, de Lonlay P, et al: Arrhythmias and conduction defects as presenting symptoms of fatty acid
oxidation disorders in children. Circulation 1999;100:2248-2253.
5. Brivet M, Boutron A, Slama A, et al: Defects in activation and transport of fatty acids. J Inher Metab Dis
1999;22:428-441.
6. Brown-Harrison MC, Nada MA, Sprecher H, et al: Very long chain acyl-CoA dehydrogenase deficiency: Successful
treatment of acute cardiomyopathy. Biochem Mol Med 1996;58:59-65.
7. Catzeflis C, Bachmann C, Hale DE, et al: Early diagnosis and treatment of neonatal medium-chain-acyl-CoA
dehydrogenase deficiency: Report of two siblings. Eur J Pediatr 1990;149:577-581.
8. Chen YT, Cornblath M, Sidbury JB: Cornstarch therapy in type I glycogen storage disease. N Engl J Med
1984;310:171-175.
9. Coates P: New developments in the diagnosis and investigation of mitochondrial fatty acid oxidation disorders. Eur
J Pediatr 1994;153:S49-S56.
10. Costa CG, Dorland L, Tavares de Almeida I, et al: The effect of fasting, long-chain-triglyceride load and carnitine
load on plasma long-chain-acylcarnitine levels in mitochondrial very long-chain-acyl-CoA dehydrogenase
deficiency. J Inher Metab Dis 1998;21:391-399
11. Davidson-Mundt A, Luder AS, Greene CL: Hyperuricemia in medium-chain-acyl-coenzyme A dehydrogenase
deficiency. J Pediatr 1992;120:444-446.
12. DiDonato S, Gellera C, Peluchetti D, et al: Normalization of short-chain-acylcoenzyme A dehydrogenase after
riboflavin treatment in a girl with multiple acylcoenzyme A dehydrogenase-deficient myopathy. Ann Neurol
1989;25:479-484.
13. Dionisi-Vici C, Burlina AB, Bertini E, et al: Progressive neuropathy and recurrent myoglobinuria in a child with
long-chain-3-hydroxyacyl-coenzyme A dehydrogenase deficiency. J Pediatr 1991;118:744-746.
14. Duran M, Wanders RJA, deJager JP, et al: 3-Hydroxydicarboxylic aciduria due to long-chain-3-hydroxyacyl-
coenzyme A dehydrogenase deficiency associated with sudden neonatal death: Protective effect of medium-
chain-triglyceride treatment. Eur J Pediatr 1991;150:190-195.
16. Gillingham M, van Calcar S, Ney D, et al: Dietary management of long-chain-3-hydroxyacyl-CoA dehydrogenase
deficiency (LCHADD). A case report and survey. J Inher Metab Dis 1999;22:123-131.
17. Gregersen N, Winter V, Jensen PKA, et al: Prenatal diagnosis of medium-chain-acyl-CoA dehydrogenase (MCAD)
deficiency in a family with a previous fatal case of sudden unexpected death in childhood. Prenat Diagn
1995;15:82-86.
18. Hagenfeldt L, Venizelos N, von Dobeln U: Clinical and biochemical presentation of long-chain-3-hydroxyacyl-CoA
dehydrogenase deficiency. J Inher Metab Dis 1995;18:245-248.
19. Hale DE, Bennett MJ: Fatty acid oxidation disorders: A new class of metabolic diseases. J Pediatr 1992;121:1-11.
20. Harding CO, Gillingham MB, van Calcar SC, et al: Docosahexaenoic acid and retinal function in children with long-
chain-3-hydroxyacyl-CoA dehydrogenase deficiency. J Inher Metab Dis 1999;22:276-280.
21. Harpey JP, Charpentier C, Paturneau-Jouas M: Sudden infant death syndrome and inherited disorders of fatty acid
-oxidation. Metab Prob Newborn 1990;58 (Suppl 1):70-80.
22. Iafolla AK, Thompson RJ, Roe CR: Medium-chain-acyl-coenzyme-A dehydrogenase deficiency: Clinical course in
120 affected children. J Pediatr 1994;124:409-415.
23. Jackson S, Bartlett K, Land J, et al: Long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency. Pediatr Res
1991;29:406-411.
24. Jackson S, Kler RS, Bartlett K, et al: Combined enzyme defect of mitochondrial fatty acid oxidation. J Clin Invest
1992;90:1219-1225.
25. Jones PJH, Kubow S: Functions of essential fatty acids. In Shils ME, et al (eds): Modern Nutrition in Health and
Disease ed 9. Philadelphia: Williams & Wilkins, 1999, pp 84-88.
26. Kmoch S, Zeman J, Hrebicek M, et al: Riboflavin-responsive epilepsy in a patient with SER209 variant form of
short-chain-acyl-CoA dehydrogenase. J Inher Metab Dis 1995;18:227-229.
1989;143:537-542.
28. Losty HC, Lee P, Alfaham M, et al: Fatty infiltration in the liver in medium-chain-acyl-CoA dehydrogenase
deficiency. Arch Dis Child 1991;66:727-728.
1982.
1987;1:1-17.
31. Millington DS, Terada N, Chace DH, et al: The role of tandem mass spectrometry in the diagnosis of fatty acid
oxidation disorders. In Coates PM, et al (eds): New Developments in Fatty Acid Oxidation. New York: Wiley Liss,
1992, p 339.
32. Moore R, Glasgow JFT, Bingham MA, et al: Long-chain-3-hydroxyacyl-coenzyme A dehydrogenase deficiency —
Diagnosis, plasma carnitine fractions and management in a further patient. Eur J Pediatr 1993;152:433-436.
33. Nada MA, Vianey-Saban C, Roe CR, et al: Prenatal diagnosis of mitochondrial fatty acid oxidation defects. Prenat
Diagn 1996;16:117-124.
34. Parini R, Invernizzi F, Menni F, et al: Medium-chain-triglyceride loading test in carnitine acylcarnitine translocase
deficiency. Insights on treatment. J Inher Metab Dis 1999;22:733-739.
35. Perper JA, Ahdab-Barmada M: Fatty liver, encephalopathy and sudden unexpected death in early childhood due to
medium-chain-acyl-coenzyme A dehydrogenase deficiency. Am J Med Path 1992;131;329-334.
36. Pitt JJ: Novel glycine conjugates in medium-chain-acyl-CoA dehydrogenase deficiency. J Inher Metab Dis
1993;16:392-398.
37. Pollitt RJ: Disorders of mitochondria long-chain-fatty acid oxidation. J Inher Metab Dis 1995;18:473-490.
39. Przyrembel H, Jakobs C, Ijlst L, et al: Long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency. J Inher Metab Dis
1991;14:674-679.
40. Report of a Joint Expert Consulation: Fats and Oils in Human Nutrition. Rome: World Health Organization,1993.
41. Rinaldo P, Schmidt-Sommerfeld E, Posca AP, et al: Effect of treatment with glycine and L-carnitine in medium-
chain-acyl-CoA dehydrogenase deficiency. J Pediatr 1993;122:580-584.
42. Roe CR, Ding J: Mitochondrial fatty acid oxidation disorders. In Scriver CR, et al (eds): The Metabolic and
pp 2297-2326.
43. Ruitenbeek W, Poels PJE, Turnbull DM, et al: Rhabdomyolysis and acute encephalopathy in late onset medium-
chain-acyl-CoA dehydrogenase deficiency. J Neurol Neurosurg Psychiatry 1995;58:209-214.
44. Saudubray JM, Martin D, de Lonlay P, et al: Recognition and management of fatty acid oxidation defects. A series
of 107 patients. J Inher Metab Dis 1999;22:488-502.
46. Sewell AC, Bender SW, Wirth S, et al: Long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency: A severe fatty
acid oxidation disorder. Eur J Pediatr 1994;153:745-750.
1976.
1983;7:280-288.
49. Treem WR, Rinaldo P, Hale DE, et al: Acute fatty liver of pregnancy and long-chain-3-hydroxyacyl-coenzyme A
dehydrogenase deficiency. Hepatology 1994;19:339-345.
50. Uauy R, Treen M, Hoffman DR: Essential fatty acid metabolism and requirements during development. Semin
Perinatol 1989;13:118-130
51. Venizelos N, Ijlst L, Wanders JA, et al: Beta-oxidation enzymes in fibroblasts from patients with
3-hydroxydicarboxylic aciduria. Pediatr Res 1994;36:111-114.
52. Wanders RJA, Ijlst L, Duran M, et al: Long-chain-3-hydroxyacyl-CoA dehydrogenase deficiency: Different clinical
expression in three unrelated patients. J Inher Metab Dis 1991;14:325-328.
53. Wanders RJA, Ijlst L, Poggi F, et al: Human trifunctional protein deficiency: A new disorder of mitochondrial fatty
acid oxidation. Biochem Biophys Res Commun 1992;180:1139-1145.
54. Wanders RJA, Vreken P, DenBoer MEJ, et al: Disorders of mitochondrial fatty acyl-CoA ß-oxidation. J Inher Metab
Dis. 1999;22:442-487.
1977;30:1269-1280.
56. Warshaw JB, Curry E: Comparison of serum carnitine and ketone body concentrations in breast- and in formula-
fed newborn infants. J Pediatr 1980;97:122-125.
57. Whyte RK, Whelen D, Hill R, et al: Excretion of dicarboxylic and w-1 hydroxy fatty acids by low birth weight infants
fed with medium chain triglycerides. Pediatr Res 1986;20:122-125.
58. Wilcken B, Carpenter KH, Hammond J: Neonatal symptoms in medium-chain-acyl-coenzyme A-dehydrogenase
deficiency. Arch Dis Child 1993;69:292-294.
59. Wilcken B, Hammond J, Silink M: Morbidity and mortality in medium-chain-acyl-CoA dehydrogenase deficiency.
Arch Dis Child 1994;70:410-412.

60. Wilcken B, Leung KC, Hammond J, et al: Pregnancy and fetal long-chain-3-hydroxyacyl coenzyme A
dehydrogenase deficiency. Lancet 1993;314:407-408.
61. Wilson CJ, Champion MP, Collins JE, et al: Outcome of medium-chain-acyl-CoA dehydrogenase deficiency after
diagnosis. Arch Dis Child 1999;80;459-462.
62. Yamaguchi S, Indo Y,-CoAtes P, et al: Identification of very-long-chain-acyl-CoA dehydrogenase deficiency in
three patients previously diagnosed with long-chain-acyl-CoA dehydrogenase deficiency. Pediatr Res
1993:34:111-113.
63. Ziadeh R, Hoffman EP, Finegold DN, et al: Medium-chain-acyl-CoA dehydrogenase deficiency in Pennsylvania:
Neonatal screening shows high incidence and unexpected mutation frequencies. Pediatr Res 1995;37;675-678.

PROTOCOL 21 — Hypercalcemia

CALCILO XD ® Low-Calcium/Vitamin D-Free Infant Formula With Iron
I. Introduction: Hypercalcemia Results from Four Disorders Described Below

A. Williams Syndrome (WS) is an autosomal dominant disorder characterized by supravalvular aortic
stenosis, which may include peripheral pulmonary stenosis, elfin facies, and psychomotor
retardation (28). Developmental delay is found in approximately 72% of patients (34). The
phenotype of WS may be due to a hemizygous defect in the elastin gene (7q11.3) (25) or genes
contiguous to the elastin locus (38) which may account for some of the vascular problems and
dysmorphism associated with WS. Hypercalcemia and central nervous symptoms may result from
deletion of adjacent genes (25).
Infantile hypercalcemia is found in approximately 40% of patients with WS and usually
resolves by 4 years of age (26, 34). A dysfunction of the human calcitonin gene receptor, a
transmembrane peptide that acts both as a calcitonin receptor and extracellular calcium sensor,
has been reported in this disorder (38). Reports of patients with WS also identify defects in
vitamin D metabolism (12, 23, 48) and calcitonin secretion (8). Nephrocalcinosis secondary to
hypercalcemia has been reported (39).
B. Osteopetrosis is a group of diseases of defective osteoclast function resulting in reduced
resorption of calcified cartilage. Consequently, patients exhibit increased skeletal mass and bone
density and abnormal bone remodeling (13). Inheritance is either autosomal recessive or
autosomal dominant. The milder dominant form exhibits in adult life (5). Autosomal recessive
malignant infantile osteopetrosis is a rare disease affecting approximately 1:200,000 live births
with increased incidence in Saudi Arabia and Costa Rica. The cause of osteopetrosis is unknown
except for a small number of patients with a carbonic anhydrase II deficiency (44).
The accumulation of bone in osteopetrotic patients results in narrowing of the cranial nerve
foramina and reduction in the bone marrow cavity (38). Immunodeficiency results from reduced
leukocyte superoxide generation (2, 22, 27). These defects can lead to hearing loss, blindness,
and/or sepsis.
C. Primary Neonatal Hyperparathyroidism (PNH) is a rare disorder resulting in excessive production
of parathyroid hormone (PTH) due to parathyroid hyperplasia (7, 17). A defect in the gene that
expresses the calcium-sensing receptor protein in parathyroid, thyroid, and renal cells (24) may be
responsible for PNH (15, 16).
Patients with PNH present early in infancy with failure to grow, anorexia, irritability, lethargy,
respiratory distress, bone demineralization, and fractures. Severe hypercalcemia (> 15 to
20 mg/dL, 3.75 to 5.00 mmol/L) and increased plasma PTH concentrations are found.
D. Idiopathic Hypercalcemia may be due, in part, to disorders that result in excessive intestinal
calcium absorption, increased resorption of bone calcium, or enhanced renal resorption.
Additionally, disturbances of vitamin D and calcium-phosphate metabolism may be evident (31,
40). Phenotypes may be benign or malignant. Any infant or child with hypercalcemia must have a
thorough clinical evaluation for diagnosis (3).

A. Growth retardation is evident in many patients with WS. Skeletal development proceeds at a
normal rate, but remains at approximately the 3rd percentile (36). Poor growth has been reported
in the first years of life (37).
B. Only 30% of patients with osteopetrosis survive until 6 years of age, with life expectancy less than
10 years (13, 20, 49). Bone marrow transplantation, beneficial in ameliorating the clinical
consequences of autosomal recessive osteopetrosis, improves survival in some patients (18, 42).
Recombinant human interferon gamma has been used with mixed success to stimulate osteoclast
activity and bone resorption (21, 22, 27). Mixed findings have also been shown with administration
of large doses of Calcitriol ® (1, 25-dihydroxycholecalciferol), an active form of vitamin D3 and a
© 2001 Ross Products Division Hypercalcemia 371
potent stimulator of osteoclastic bone resorption (20, 49). Hematopoietic stem cell transplantation
is successful in correcting hematologic manifestations (10). Failure to grow and poor stature are
common findings in patients with severe osteopetrosis (43). Growth retardation may be
exacerbated by poor dentition and difficulty ingesting adequate nutrient intake (52).
C. PNH is fatal if not recognized and treated early in life. Parathyroidectomy normalizes plasma
calcium concentration and improves prognosis (7, 17). Pharmacologic therapy to activate the
calcium-sensing receptor is undergoing clinical trial.
D. Outcomes for patients with idiopathic hypercalcemia are variable and depend on the specific
disorder. Latent nephrocalcinosis has been reported (40).

A. The Disorder
1. Hypercalcemia may be identified in several disorders, including the following:
a. Williams syndrome.
b. Osteopetrosis (marble bone disease) .
1) Autosomal-recessive.
2) Autosomal-dominant, types I and II.
c. Neonatal hyperparathyroidism.
d. Idiopathic infantile hypercalcemia.
B. Differential Diagnosis
1. For methods of diagnosis, see references 1, 4-6, 32, 33, 35, 41, 44.
2. Therapy depends on disorder present.

1. Restrict dietary calcium (Ca) and vitamin D to that tolerated by patient to maintain treatment
plasma total Ca and 1,25-dihydroxyvitamin D concentrations.

A. Plasma Calcium Concentration
1. Maintain plasma total Ca concentration in near normal to normal range: 1.9 to 2.7 mmol/L
(7.6-10.8 mg/dL) (12, 14, 18, 19, 54).
B. Plasma 1,25-Dihydroxyvitamin D Concentration
1. Maintain normal plasma concentration (12, 23, 31, 54) (52-60 pg/mL, radioreceptor binding
assay, Quest Diagnostics, San Juan Capistrano, CA).
Warning: In osteopetrosis, high doses of Calcitriol result in elevation of
1,25-dihydroxyvitamin D.
adults.
a. Prevent rickets.

A. Calcium
1. Prescribe Ca intake that produces normal or near normal plasma Ca concentration.
a. Ca intakes ranging from 50 to 400 mg/day have been used (4, 9, 12, 14, 21, 48, 53).
2. Dietary Ca restriction is usually just one component of total treatment for osteopetrosis.
B. Vitamin D
1. No additional dietary vitamin D or vitamin D supplements should be added to Ca-restricted
diet.
2. Do not prescribe mineral/vitamin supplements that contain vitamin D or Ca.
372 Hypercalcemia © 2001 Ross Products Division

3. Exception: Patients with osteopetrosis who develop rachitic changes are treated with either
Calcitriol (1-2 µg/kg per day) or interferon gamma (1.5 µg/kg subcutaneous injection 3 times
per week), in addition to other therapies (20, 22).
C. Protein
1. Prescribe amount that promotes normal growth and development (Table 21-1, p 373).
D. Energy
1. Prescribe amount that should support normal weight and length gain for infants and children
and maintain appropriate weight for height for adults (Table 21-1, p 373).
E. Fluid
for each kcal ingested (3).
Note: Interferon-gamma therapy in patients with osteopetrosis may elevate body
temperature (21) resulting in increased water loss.

A. Calcium
1. Calculate amount of Ca supplied by Calcilo XD (Table 21-3, p 374), beikost, or table foods
required to fill protein prescription.
a. Ca content of beikost (baby food) may be obtained by contacting the following
manufacturers:
1-800-233-2468 1-800-443-7237 Pittsburgh, PA 15219
1-800-872-2229
b. Ca content of table foods may be obtained from the USDA Nutrient Data Laboratory; Ph
(301) 504-0630; Fax (301) 504-0632; web site www.nal.usda.gov.fnic/foodcomp.
1) General guidelines:
i. Meat/meat substitutes.
a) Exclude soybeans and soybean products (tofu, miso, natto, and tempeh),
canned salmon, smelt, mackerel, sardines with bones, canned shrimp, baked
beans, northern beans, French beans, mung beans, California red kidney
beans.
ii. Fruits.
a) Exclude juices with added calcium.
iii. Vegetables
a) Exclude collard, dandelion and turnip greens, kale, oriental radish, rhubarb,
and spinach.
Warning: Avoid all prepackaged foods containing milk and milk products, all soups
prepared with milk, and batter-dipped fried foods.
2. If additional Ca is needed, sources of Ca may be added to diet.
a. For infants, infant formula with iron may be used (Table 21-2, p 373).
b. For children, food sources of Ca are listed in Table 21-2, p 373.
3. Local water supply may contain significant amounts of Ca and should be assayed, unless
deionized water is used.
B. Protein
1. Calculate amount of Calcilo XD (Table 21-3, p 374) and beikost or table foods containing little
or no Ca required to fill protein prescription.
a. Weigh Calcilo XD powder on scale that reads in grams because of variability of household

b. See Table 21-3 (p 374, footnote 1) for approximate weight of Calcilo XD powder in level,
2. Requirements for children and adults may be met using beikost, table foods, or Calcilo XD.
C. Energy
1. Calculate energy provided by Calcilo XD (Table 21-3, p 374) and beikost or table foods
containing little or no Ca required to fill protein and Ca prescriptions.
3. Provide any remaining prescribed energy by concentrating Calcilo XD, or by supplementing
with Polycose ® Glucose Polymers powder (23 kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL)
(Appendix 9, p A-9), sugar (48 kcal/Tbsp), or other Ca-free energy sources.
1. To prepare 20-kcal/fl-oz formula, add sufficient boiled, cooled water to three scant scoops
(19.3 g) of Calcilo XD to yield 5 fl oz. Tap water may replace boiled, cooled water when
preparing Calcilo XD for older infants and children.
a. To make different amounts of a 20 kcal/fl oz formula, follow appropriate directions below
using level measures:
1) To prepare 1-8 fl oz bottle of formula, add water to 31 g (1/4 cup + 1 tsp) of Calcilo
XD to make 8 fl oz.
2) To make 1 L of formula, add water to 131 g (1-1/4 cups) of Calcilo XD to make 1 L.
3) To make 1 qt of formula, add water to 125 g (1 cup + 2-1/2 Tbsp) of Calcilo XD to
make 32 fl oz.
can and store in dry place (not in refrigerator). Use within 1 month after opening.
3. Warm or cool prepared Calcilo XD to room temperature before feeding to infants. Shake well
before feeding.
4. Do not use microwave oven to warm infant formula. Unevenly heated formula can burn
5. Notify parents or caretakers when they may discontinue use of aseptic technique in making
formula.
Warning: Municipal water may contain substantial quantities of calcium. Contact the
local public utilities office for information. Bottled deionized water may be
used to prepare Calcilo XD.
E. Diet Guide
each diet change.

a. See Table 21-3, p 374, for composition of Calcilo XD.
2. Check diet to determine if it supplies Recommended Dietary Intakes (RDIs) of minerals
(except Ca) and vitamins (except vitamin D) (Appendices 13 and 14, pp A-14 and A-15).
not available.
b. If Calcilo XD mixture provides < 100% of RDIs for infants, supplement diet with needed
minerals and vitamins — free of Ca and vitamin D — if not provided by beikost or table
supplements).

B. Osmolarity
b. Osmolarity of Calcilo XD is 2.02 mosm/g of powder.
2. If osmolarity is > 450 mosm/L for neonates (29), > 750 mosm/L for toddlers, > 1,000 mosm/L
for adults (46), or greater than tolerated by patient, increase water content of prescribed
renal solute load.
recalculate.

A. Plasma Calcium Concentration
1. Evaluate weekly by quantitative methods until patient is 6 months of age and monthly
thereafter, or as indicated.
2. If plasma Ca concentrations remain high, reduce Ca intake by 5% to 10% and reevaluate in
1 week.
3. Pharmacologic therapy may also need to be modified in response to elevated calcium
concentrations.
B. Urinary Calcium Excretion
1. Evaluate monthly until patient is 6 months of age and every 3 months thereafter.
C. Plasma 1,25-Dihydroxyvitamin D Concentration
1. Elevated plasma concentrations have been found in patients with WS (12, 23) and
osteopetrosis (27, 44, 50).
2. Measure as needed to maintain normal plasma concentration (ie, 52-60 pg/mL).
D. Protein Status
1. Evaluate plasma albumin concentration every 3 months until patient is 1 year of age and
a. Increase prescribed protein by 5% to 10% and reevaluate plasma albumin concentration
in 1 month.
b. If plasma albumin concentration continues below standard, repeat above process until
E. Rachitic Changes in Osteopetrosis
1. Evaluate plasma alkaline phosphatase concentration routinely to maintain normal plasma
concentration.
a. If plasma alkaline phosphatase concentration is elevated, reevaluate both nutrition
support and medical treatment and modify if needed.
2. Evaluate radiographs of long bones routinely.
F. Iron Status

2) Evaluate plasma ferritin concentration monthly on increased iron supplementation.
standards).
b. Hemoglobin and hematocrit improve with therapy but remain low (21).
c. Measure neutrophils and platelets as needed to monitor hematologic status. Nutrition
support alone may not normalize leukoerythroblastic anemia (space-occupying lesions of
marrow, decreased immature granulocytes, normal leukocytes, and low erythrocyte
concentrations) and thrombocytopenia found in osteopetrosis.
G. Growth Status
infants, children, and adults will fall above or below these percentiles. Growth retardation
has been described in these disorders (32, 37, 51, 53).
achieved.
Warning: Use of recombinant human interferon gamma therapy for osteopetrosis may
cause anorexia and weight loss (21, 22).
H. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of Ca, phosphorus, vitamin D, protein, and energy weekly in infants and
monthly for children and adults.
not available.
program does not quantitate vitamin D.
Warning: Ca prescription must be modified based on frequently obtained plasma Ca
concentrations and growth in infants and children. Side effects of severe
anemia as seen in patients with osteopetrosis may negatively affect appetite.
I. Clinical Summary
A. Example
Establish and fill prescription for 4-month-old girl weighing 5.0 kg using Recommended Daily
and 374.

Calcium < 50 mg total = < 50 mg/day
Medical Food Mixture Measure Calcium Protein Energy
(mg) (g) (kcal)
Calcilo XD 111 g < 50.0 12.6 575
Add water to make 750 mL (25 fl oz). Offer additional water ad libitum.
Total per day < 50.0 12.6 573

Total per kg < 10.0 2.5 115
is < 100 mosm.

Hypercalcemia
Age Nutrient
Protein1 Energy1 Fluid2
Infants
0 to < 3 mo 3.00 - 2.20 120 (145 - 95) 160 - 125
3 to < 6 mo 3.00 - 2.20 115 (145 - 95) 160 - 130
6 to < 9 mo 2.50 - 2.00 110 (135 - 80) 145 - 125
9 to < 12 mo 2.50 - 2.00 105 (135 - 80) 135 - 120

Girls and Boys
1 to < 4 yr ≥ 23.0 1,300 ( 900 - 1800) 900 - 1,800
4 to < 7 yr ≥ 30.0 1,700 (1300 - 2300) 1,300 - 2,300
7 to < 11 yr ≥ 34.0 2,400 (1650 - 3300) 1,650 - 3,300
Women
11 to < 15 yr ≥ 46.0 2,200 (1500 - 3000) 1,500 - 3,000
15 to < 19 yr ≥ 46.0 2,100 (1200 - 3000) 1,200 - 3,000
≥ 19 yr ≥ 50.0 2,100 (1400 - 2500) 1,400 - 2,500
Men
11 to < 15 yr ≥ 45.0 2,700 (2000 - 3700) 2,000 - 3,700
15 to < 19 yr ≥ 59.0 2,800 (2100 - 3900) 2,100 - 3,900
≥ 19 yr ≥ 63.0 2,900 (2000 - 3300) 2,000 - 3,300
1
From reference 11.
2
From reference 3. Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to children and
TABLE 21-2. Foods That May Be Added IF Additional Dietary Calcium Is Required
Food List Measure Calcium Protein Energy

(mg) (g) (kcal)
Dairy Products 1
Buttermilk 8 fl oz 285 8.1 99
Cheese, American, pasteurized, processed 1 oz 174 6.2 106
Cheese, Cheddar 1 oz 204 7.1 114
Cheese, cottage (2% fat) 1 cup 155 31.1 203
Cheese, Mozzarella (part skim milk) 1 oz 183 6.9 72
Ice cream, vanilla (regular) 1/2 cup 84 2.3 133
Ice cream, vanilla (French; soft serve) 1/2 cup 113 3.5 185
Milk (2% fat) 8 fl oz 297 8.1 121
Milk, goat's 8 fl oz 326 8.7 168
Milk, whole (3.3% fat) 8 fl oz 291 8.0 150
Sherbet, orange 1/2 cup 40 0.8 102
Yogurt, plain (made with whole cow's milk) 8 fl oz 296 8.5 150
Infant Formulas
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed 100 mL 71 1.86 68
2
2
Isomil ® Soy Formula With Iron, Ready to Feed 100 mL 71 1.66 68
2
Similac ® With Iron Infant Formula, Ready to Feed 100 mL 53 1.40 68
1
USDA Nutrient Data Laboratory website (www.nal.usda.gov/fnic/foodcomp).
2

TABLE 21-3. Nutrient Composition of Calcilo XD ® Low-Calcium/Vitamin D-Free
Infant Formula With Iron1, 2
Nutrient Per 100 g Powder

Energy, kcal 513
Protein, g 11.4
Carbohydrate, g 52.3
Fat, g 28.7
Linoleate, g 6.66
Minerals
Calcium, mg < 50
Chloride, mg/mEq 292/8.24
Copper, mg 0.46
Iodine, µg 31.0
Iron, mg 9.2
Magnesium, mg 31.0
Manganese, µg 26.0
Phosphorus, mg 128.0
Potassium, mg/mEq 420/10.74
Selenium, µg 11.3
Sodium, mg/mEq 125/5.4
Zinc, mg 3.8
Vitamins
A, µg RE 462
D, µg 0
E, mg α-TE 6.7
K, µg 41.0
Ascorbic acid, mg 46.0
Biotin, µg 23.0
B6, mg 0.31
B12, µg 1.28
Choline, mg 62.0
Folacin, µg 77.0
Inositol, mg 123.0
Niacin, mg 5.4
Pantothenic acid, mg 2.3
Riboflavin, mg 0.77
Thiamine, mg 0.51
Other
Osmolarity, mosm/100 g 202
Estimated potential renal solute load, mosm/100 g 93
1
Approximate weights of Calcilo XD Powder measured in level, dry US standard household
measures:
1 scoop = 8 g powder
1 Tbsp = 8.5 g powder
1/4 cup = 28 g
1/2 cup = 57 g
1 cup = 103 g
2
19.3 g powder with water added to yield 5 fl oz supplies 20 kcal/fl oz.

TABLE 21-4. Diet Guide for Children and Adults With Hypercalcemia
Date: ______/__________/__________
Mo Day Year
Birthdate: _________/__________/__________ Age:
Mo Day Year
Length: (cm/in) Weight: (kg/lb)
Medical Food Mixture Measure Calcium Protein Energy

(mg) (g) (kcal)
Calcilo XD g/Tbsp/cup
Add water to make mL/fl oz
Food List Measure/Servings
Fat
Fruit
Meat oz
Starch/Bread
Vegetables
Total per day
Total per kg
Comments:
______________________________________________
Nutritionist

TABLE 21-5. Hypercalcemia Clinical Summary Sheet
376 Hypercalcemia

Mo Day Year

Ht Wt HC Calcium Serum Serum Alk Ferritin Hgb Albumin Platelets Neutrophils Calcium Protein Energy
Serum Urine Phos 1,25-OH D Phos
9 9
(mo/d/yr) (cm) (kg) (cm) (µmol/L) (µmol/mg Cr) (µmol/L) (pg/mL) (µ/L) (ng/mL) (g/dL) (g/dL) (x 10 /L) (x 10 /L) (mg) (g) (kcal)
REFERENCES
1. Andersen PE, Bollerslev J: Heterogeneity of autosomal dominant osteopetrosis. Radiology 1987;164:223-225.
2. Beard CJ, Key LL, Newburger PE, et al: Neutrophil defect associated with malignant osteopetrosis. J Lab Clin Med
1986;108:498-505.
3. Behrman RE, Kleigman RM, Arvin AA: Nelson Textbook of Pediatrics, ed 15. Philadelphia: WB Saunders Co,
1996.
4. Bergman H, Brown J, Rogers A, Bourke E: Osteopetrosis with combined proximal and distal renal tubular acidosis.
Am J Kidney Dis 1992;2:357-362.
5. Bollerslev J: Osteopetrosis: Genetic and epidemiological study. Clin Genet 1987;31:86-90.
6. Brewer CM, Morrison N, Tolmie JL: Clinical and molecular cytogenetic (FISH) diagnosis of Williams syndrome.
Arch Dis Child 1996;74:59-61.
7. Cakmak O, Agis ER, Tezic T, Ates G: Primary hyperparathyroidism in infancy: A case report. J Pediatr Surg
1996;31:437-438.
8. Culler FL, Jones KL, Deftos LJ: Impaired calcitonin secretion in patients with Williams syndrome. J Pediatr
1985;107:720-729.
9. Dorantes LM, Mejia AM, Dorantes S: Juvenile osteopetrosis: Effects on blood and bone of prednisone and a low
calcium, high phosphate diet. Arch Dis Child 1986;61:666-670.
10. Eapen M, Davies S, Ramsay NK, Orehard PJ: Hematopoietic stem cell transplantation for infantile osteopetrosis.
Bone Marrow Transplant 1998;22;941-946.
12. Garabédian M, Jacqz E, Guillozo H, et al: Elevated plasma 1,25-dihydroxyvitamin D concentrations in infants with
hypercalcemia and elfin facies. N Engl J Med 1985;312:948-952.
13. Gerritsen EJA, Vossen JM, van Loo IHG, et al: Autosomal recessive osteopetrosis: Variability of findings at
diagnosis and during the natural course. Pediatrics 1994;93:247-253.
14. Goodyer PR, Frank A, Kaplan BS: Observations on the evolution and treatment of idiopathic infantile
hypercalcemia. J Pediatr 1984;105:771-773.
15. Ho C, Connor DA, Pollak CR, et al: A mouse model of human familial hypocalcuric hypercalcemia and neonatal
severe hyperparathyroidism. Nat Genet 1995;11:389-394.
16. Hosokawa YM, Pollak MR, Brown EM, Arnold A: Mutational analysis of the extracellular Ca (2+)-sensing receptor
gene in human parathyroid tumor. J Clin Endocrinol Metab 1995;80:3107-3110.
17. Huang CB, Huang SC, Chou FF, Chen WJ: Primary hyperparathyroidism in children: Report of a case and a brief
history of the literature. J Formos Med Assoc 1993;92:1095-1098.
18. Kaplan FS, August CS, Fallon MD, et al: Successful treatment of infantile malignant osteopetrosis by bone-marrow
transplantation (case report). J Bone Joint Surg 1988;70:617-623.
19. Kaplan P, Kirchner M, Watters G, Costa MT: Contractures in patients with Williams syndrome. Pediatrics
1989;84:895-899.
20. Key L, Carnes D, Cole S, et al: Treatment of congenital osteopetrosis with high dose calcitriol. N Engl J Med
1984;310:409-415.
21. Key LL, Oexmann MJ, Green L: Nutrition in patients with osteopetrosis on interferon gamma (editorial comments).
Nutrition 1997;13:988-990.
22. Key LL, Ries WL, Rodriguiz RM, Hatcher HC: Recombinant human interferon gamma therapy for osteopetrosis.
J Pediatr 1992;121:119-124.
23. Knudtzon J, Aksnes L, Akslen LA, Aarskog D: Elevated 1,25-dihydroxyvitamin D and normocalcaemia in presumed
familial Williams syndrome. Clin Genet 1987;32:369-374.
24. Kobayashi M, Tanaka H, Tzuzuku K, et al: Two novel mutations in calcium-sensing receptor gene associated with
neonatal severe hyperparathyroidism. J Clin Endocrin Metab 1997;82:2716-2719.
25. Kotzot D, Bernasconi F, Brecevic L, et al: Phenotype of the Williams-Beuren syndrome associated with
hemizygosity at the elastin locus. Eur J Pediatr 1995;154:477-482.
26. Kruse K, Pankau R, Gosch A, Wohlfahrt K: Calcium metabolism in Williams-Beuren syndrome. J Pediatr
1992;121:902-907.
27. Kubo T, Tanaka H, Ono H, et al: Malignant osteopetrosis treated with high doses of 1-α-hydroxyvitamin D3 and
interferon gamma. J Pediatr 1993;123:264-268.
28. Lashkari A, Smith AK, Graham JM: Williams-Beuren syndrome: An update and review for the primary physician.
Clin Pediatr 1999;38;189-208.
1982.
1987;1:1-17.
31. McGraw ME: Vitamin D metabolites in idiopathic infantile hypercalcemia. Arch Dis Child 1986;61:1246.

32. Morris CA, Demsey SA, Leonard CO, Dilts C, Blackburn BL: Natural history of Williams syndrome: Physical
characteristics. J Pediatr 1988;113:318-326.
33. Morris CA, Leonard CO, Dilts C, Demsey SA: Adults with Williams syndrome. Am J Med Genet
1990;6(suppl):102-107.
34. Nicholson WR, Hockey KA: Williams syndrome: A clinical study of children and adults. J Pediatr Child Health
1993;29:468-472.
35. Ohlsson A, Cumming WA, Paul A, Sly WS: Carbonic anhydrase II deficiency syndrome: Recessive osteopetrosis
with renal tubular acidosis and cerebral calcification. Pediatrics 1986;77:371-381.
36. Pankau R, Paitsch CJ, Gosch A, et al: Statural growth in Williams Beuren syndrome. Eur J Pediatr
1992;151:751-755.
37. Partsch CJ, Dreyer G, Gosch A, et al: Longitudinal Evaluation of growth, puberty, and bone maturation in children
with Williams syndrome. J Pediatr 1999;134:82-89.
38. Perez-Jurado LA, Li X, Francke U: The human calcitonin receptor gene (CALCR) at 7q21.3 is outside the deletion
associated with Williams syndrome. Cytogenet Cell Genet 1995;70:246-249.
39. Pober BR, Lacio RB, Rice C, et al: Renal findings in 40 individuals with Williams syndrome. Am J Med Genet
1993;46:271-274.
40. Pronicka E, Rowinska E, Kulczycka H, et al: Persistent hypercalcinuria and elevated 25-hydroxyvitamin D3 in
children with infantile hypercalcaemia. Pediatr Nephrol 1997;11:2-6.
41. Ruprecht A, Wagner H, Engel H: Osteopetrosis: Report of a case and discussion of differential diagnosis. Oral
Surg Oral Med Oral Pathol 1988;66:674-679.
42. Schroeder RE, Johnson FL, Silberstein MJ, et al: Longitudinal follow-up of malignant osteopetrosis by skeletal
rediography and restriction fragment lengths polymorphism analysis after bone marrow transplantation.
Pediatrics 1992;20:986-989.
43. Shapiro F: Osteopetrosis: Current clinical considerations. Clin Orthop 1993;294:34-44.
44. Sly WS, Shah GN: The carbonic anhydrase II deficiency syndrome: Osteopetrosis with renal tubular acidosis and
cerebral calcification. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of Inherited Disease, ed 8.
New York: McGraw-Hill Medical Publishing Division, 2001, pp 5331-5343.
1976.
1983;7:280-288.
1989;143:828-832.
48. Taylor AB, Stern PH, Bell NH: Abnormal regulation of circulating 25-hydroxyvitamin D in the Williams syndrome.
N Engl J Med 1982;306:972-975.
49. van Lie Peters EM, Aronson DC, Everts V, Dooren JL: Failure of calcitriol treatment in a patient with malignant
osteopetrosis. Eur J Pediatr 1993;152:818-821.
50. Whyte MP, Murphy WA, Fallon MD, et al: Osteopetrosis, renal tubular acidosis, and basal ganglia calcification in
three sisters. Am J Med 1980;69:64-74.
51. Wu YO, Sutton VR, Nickerson E, et al: Delineation of the common critical region in Williams' syndrome and
clinical correlation of growth, heart defects, ethnicity, and parental origin. Am J Med Genet 1998;78:82-89.
52. Williams R, Wang W: Managing osteopetrosis in children: a nutrition challenge. J Amer Diet Assoc
1996:96:172-175.
53. Yu JS, Oates RK, Walsh KH, Stuckey SJ: Osteopetrosis. Arch Dis Child 1971;46:257-263.
54. Zerwekh JE, Marks SC, McGuire JL: Elevated serum 1,25-dihydroxyvitamin-D in osteopetrotic mutations in three
species. Bone Miner 1987;2:193-199.

PROTOCOL 22 — Gyrate Atrophy of the Choroid and Retina

CYCLINEX ®-1 and CYCLINEX ®-2 Amino Acid-Modified Medical Foods
I. Introduction
Gyrate atrophy (GA) of the choroid and retina results from a defect in the enzyme ornithine-δ-
aminotransferase (OAT) (Figure S). A consequence of OAT deficiency is progressive chororetinal
degeneration starting in the first decade of life with myopia, night-blindness and loss of peripheral
vision. Without treatment, tunnel vision and blindness are evident by the 3rd or 4th decade of life.
Cataracts are common in all untreated patients by late in the 2nd decade of life (3, 21, 47).
Biochemical consequences of OAT defect are elevated plasma ornithine (ORN) concentration ranging
from 400 to 1,400 µmol/L and reduced concentration of plasma glutamate, glutamine, lysine, creatine,
and its precursor, guanidinoacetate. In addition, GA patients have low creatine and creatine phosphate
concentrations in skeletal muscle and brain that negatively affect energy metabolism (31, 42).
Mutations in OAT demonstrate allelic heterogeneity that may account for differences in clinical and
biochemical phenotypes (15, 27). Some patients with gyrate atrophy show a reduction in plasma ORN
concentrations in response to pharmacologic doses of pyridoxine (6, 14, 23, 41).
The actual incidence of gyrate atrophy is not known. There are over 150 documented cases of gyrate
atrophy; one-third are of Finnish origin.
Dietary protein
Body protein breakdown
Glutamate + -
NH4* + HC03
Ornithine*
Ornithine-δ-
aminotransferase
Urea Cycle
Citrulline
Urea
Arginine*
* Accumulates in untreated gyrate atrophy

Indicates site of enzyme malfunction
Figure S. Ornithine metabolism in gyrate atrophy of the choroid and retina.

Pyridoxine-responsive patients have a milder phenotype and preservation of visual acuity to later in life
than patients who do not respond to vitamin B6 (40). Dietary restriction of arginine (ARG) has been
successfully used to reduce plasma ORN and ARG concentrations. Long-term reduction in plasma
ORN concentration has reduced progression of retinal atrophy and improved visual function (19, 20,
21, 28, 38, 40). Creatine therapy improves muscle and brain creatine concentrations, but does not
prevent progression of retinal degradation (31, 42).
© 2001 Ross Products Division Gyrate Atrophy 385

A. The Defect
1. GA results from defect in OAT (22, 32, 40).
B. Diagnostic Studies
1. Diagnostic studies should be conducted in any person with the following symptoms:
a. Concentration of plasma ORN 10 to 15 times greater than normal (400 - 1,400 µmol/L)
and hyperornithinuria (21, 42, 48, 49).
b. Retinopathy of unknown etiology. The following progression of visual impairment may
occur in patients with GA (3, 40):
1) 1st decade of life: myopia and night-blindness.
2) 2nd decade of life: progressive loss of peripheral vision.
3) 3rd decade of life: cataracts
4) 4th and 5th decades of life: progressive impairment leading to total blindness.
2. See references 8, 32, 40, and 47 for methods of diagnosis.

1. Restrict dietary ARG to intake that maintains near normal plasma concentrations of ARG and
ORN (19, 32, 48).

1. Prescribe pharmacologic doses of pyridoxine if any residual enzyme activity is present.
2. Pyridoxine-responsive patients should be stabilized and maintained on appropriate dose of
pyridoxine before beginning nutrition support.

A. Plasma ORN Concentration
1. Maintain 2- to 4-hour postprandial plasma concentrations < 200 µmol/L when measured by
quantitative methods (47) or in normal range for age established in laboratory used.
a. Biochemical control has been classified as good (< 200 µmol/L), fair (200 - 400 µmol/L),
and poor (> 400 µmol/L).
b. In practice, obtaining blood 2 to 4 hours postprandially is not always possible. Acceptable
(Practical Aspect of Nutrition Support, p viii).
B. Plasma ARG Concentration

1. Maintain 2- to 4-hour postprandial plasma ARG concentrations at the following approximate
means for age:
Age (yr) Mean ± SD for Age
Infants and children (birth < 5) (29) 65 ± 40 µmol/L
Children and adolescents (5 < 18) (1) 89 ± 20 µmol/L
Adults (> 18) (1) 82 ± 25 µmol/L
C. Plasma Ammonia Concentration

1. Maintain normal concentrations of plasma ammonia < 35 µmol/L or within normal limits in
laboratory used.
D. Growth and Nutrition Status

adults.
2. Maintain normal nutrition status (7, 48).
1. Arrest progression of atrophy of choroid and retina and preserve or improve visual function.
386 Gyrate Atrophy © 2001 Ross Products Division

A. Pyridoxine Therapy
1. Some patients with GA may respond to pharmacologic doses of pyridoxine (vitamin B6):
a. Doses of 15 to 1500 mg of pyridoxine administered for 2 to 8 weeks have been used (6,
24, 28, 39, 40, 52).
b. Biochemical response to pyridoxine therapy is exhibited by up to 60% reduction in plasma
ORN (6, 14 , 23, 24, 39, 40, 51, 52).
c. A 2-week trial of pyridoxine therapy (300 - 600 mg/day) is suggested for all newly
diagnosed patients (40).
Warning: Prolonged use of high doses of pyridoxine results in peripheral
neuropathy (36).
B. L-ARG
1. L-ARG is an essential amino acid in patients with GA (49) and a precursor of ORN.
2. Prescribe ARG intake that promotes goals of nutrition support (Table 22-1, p 387).
3. Requirements vary widely:
a. From patient to patient, depending on activity of OAT and responsiveness to pyridoxine
therapy.
1) Age.
2) Growth rate.
3) Adequacy of protein and energy intakes.
4) State of health.
5) Plasma ORN concentrations
i. Hyperornithinemia and ornithinuria result in increased excretion of ARG (47, 49).
4. ARG intake suggested for beginning therapy depends on whether patient is responsive to
pyridoxine. Since most GA patients are not pyridoxine-responsive (47, 49), initial ARG
prescription should be at lower limit of ranges listed in Table 22-1, p 387.
5. Changing requirements of patients are determined by frequent monitoring of plasma ARG
concentrations (Section IX, Suggestion Evaluation of Nutrition support, p 383).
a. Hypoargininemia secondary to over-restriction of ARG may result in concomitant
hyperammonemia (28) and urinary excretion of orotic acid (30, 40).
Warning: ARG deficiency results in poor wound healing (4, 50), generalized skin
lesions (11), growth retardation (53), and hyperammonemia (28).
C. Protein
1. Prescribe, initially, amount at highest end of Recommended Dietary Allowances (RDAs) for
age (Table 22-1, p 387) (12, 13, 16, 18, 44).
Warning: Inadequate protein intake will result in failure to thrive in infants; weight loss,
low plasma transthyretin concentration, osteopenia, and hair loss in children
and adults. Excess protein intake will promote ammonia production and
increase the patient's requirement for ARG (7).
D. Energy
1. Prescribe amount that will support normal weight gain in infants and children and maintain
appropriate weight for height for adults (Table 22-1, p 387).
2. Requirements will vary widely and may be greater than normal when L-amino acids supply
in children, and weight loss in adults. Weight loss will result in elevated
plasma ARG concentration as a result of protein catabolism. Poor growth
results in lower than expected tolerance of ARG.
E. Fluid

A. Pyridoxine
1. Administer orally with each feed or several times per day, if beneficial.
2. Contact pharmacist for sources of pyridoxine.
B . L-ARG
(Table 22-2, p 387) required to fill ARG prescription.
a. Low iron infant formula, whole cow's milk, and evaporated milk should not be used as
ARG source for infants.
2. Measure liquid infant formula and whole cow's milk with disposable syringe. Weigh powdered
infant formula on scale that reads in grams
3. Add beikost or table foods (Table 22-2, p 387) to gradually displace ARG provided by infant
formula after infant is 3 to 4 months of age or developmentally ready.
specified amounts to fill ARG prescription.
C. Protein
table foods (Table 22-2, p 387) required to fill ARG prescription.
3. Supply any remaining prescribed protein with Cyclinex (Table 22-4, p 402).
a. Cyclinex-1 is for infants and toddlers and Cyclinex-2 is for children, adolescents, and
adults but may be used at earlier age if child's appetite is small.
b. Weigh Cyclinex powder on scale that reads in grams because of variability of household
c. See Table 22-4 (p 402, footnote 3) for approximate packed weight of Cyclinex powder in
D. Energy
(Table 22-2, p 387) and Cyclinex (Table 22-4, p 402) required to fill ARG and protein prescriptions.
3. Provide remaining prescribed energy with Polycose ® Glucose Polymers powder (23 kcal/Tbsp,
3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9); Pro-Phree ® Protein-Free Energy Module
With Iron, Vitamins & Minerals (Appendix 11, p A-10); sugar (48 kcal/Tbsp); or Free Foods B
(Table 22-2, p 387), depending on age of patient.
1. Add sufficient boiled, cooled water to infant formula, Cyclinex, and carbohydrate to yield
prescribed volume. Tap water may replace boiled, cooled water when preparing Cyclinex for
can and store in refrigerator. Use within 1 month after opening.

8. For children and adults, chill Cyclinex medical food mixture to improve taste.
F. Diet Guide
each diet change.

a. See Table 22-2, p 387, for composition of infant formulas, foods, and whole cow's milk
and Table 22-4, p 402, for composition of Cyclinex.
vitamins (Table 22-4, p 402, and Appendices 4 through 7, 13, and 14, pp A-4 to A-7, A-14 and
A-15).
not available.
b. If Cyclinex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
supplements).
B. Osmolarity
of Cyclinex mixture is in acceptable range.
b. Osmolarity per gram of Cyclinex is listed in Appendix 19, p A-21.
renal solute load.
recalculate.

A. Plasma ARG and ORN Concentrations
1. Initial.
approximate dietary ARG requirements are known.
2. Ongoing.
b Evaluate plasma concentrations of ARG and ORN by quantitative methods weekly until
the patient is 12 months of age and monthly thereafter.

3. Unacceptable ARG and/or ORN Concentrations.
a. If plasma ARG concentration is below lower limit of normal or is not detected, ORN is
< 100 µmol/L, patient has ingested full prescription, and hyperammonemia (> 35 µmol/L)
is present:
1) Immediate intervention using intravenous ARG hydrochloride may be required.
2) Once hyperammonemia is corrected and patient's condition is stabilized, add 75 mg
ARG to ARG prescription and then reevaluate ARG and ORN concentrations in 3 days.
3) If plasma ARG concentration continues undetected, repeat above process until ARG
and ORN values are in treatment range.
b. If plasma ARG concentration is below lower limit of normal or is not detected, ORN is
< 100 µmol/L, patient has ingested full prescription, and hyperammonemia (> 35 µmol/L)
is not present:
1) Add 75 mg ARG to ARG prescription and reevaluate ARG and ORN concentrations in
3 days.
2) If plasma ARG concentration continues undetected, repeat above process until ARG
and ORN values are in treatment range.
c. If plasma ORN concentration is between 200 and 400 µmol/L, ARG concentration is in
normal range, and patient has ingested full prescription:
1) Decrease ARG prescription by 30 mg and reevaluate plasma ARG and ORN
2) If plasma ORN concentration continues between 200 and 400 µmol/L, repeat above
d. If plasma ORN concentration is > 400 µmol/L, patient is not ill and has not ingested more
ARG or significantly less protein and energy than prescribed:
1) Decrease ARG prescription by 60 mg and reevaluate plasma ARG and ORN
2) If plasma ORN concentration is > 400 µmol/L, repeat above process until value is in
treatment range.
Warning: Elevated plasma ORN concentrations may result in subnormal plasma
concentrations of lysine and increased urinary excretion of cystine, lysine,
ARG, and glutamine (3). Hemolysis or mishandling of sample may over-
estimate plasma ORN concentrations.
B. Protein Status
concentration in 1 month. If plasma ARG and ORN concentrations are in treatment range,
use Cyclinex to increase protein.
C. Iron Status
D. Growth Status
achieved.
E. Nutrient Intake
and 25, pp A-26 and A-27).
2. Evaluate intakes of ARG, protein, and energy before each blood test.
not available.
F. Clinical Summary
A. Example 1
Establish and fill prescription for 3-month-old infant weighing 5.6 kg using Recommended Daily
and 402.
ARG 35 mg x 5.6 kg = 196 mg/day
Medical Food Mixture Measure ARG Protein Energy
(mg) (g) (kcal)
Similac With Iron Ready to Feed 478 mL 196 6.7 325
Cyclinex-1 60 g 0 4.5 306
Pro-Phree 25 g 0 0.0 128
Total per day 196 11.2 759

load is < 140 mosm.
B. Example 2
Establish and fill prescription for 2-year-old boy weighing 13.0 kg using Recommended Daily
and 402.

Protein = 13.0 g
Energy = 1,430 kcal
Fluid = 1,430 mL
(mg) (g) (kcal)
Cyclinex-1 76 g 0 5.7 388
Pro-Phree 76 g 0 0.0 388
Food List Servings

Fats 2 10 0.2 70
Fruits 3 75 2.1 195
Total per day 325 13.0 1,436
C. Example 3
Establish and fill prescription for 12-year-old girl weighing 40.0 kg using Recommended Daily
and 402.
Protein = 23.0 g
Energy = 2,200 kcal
Fluid = 2,400 mL
(mg) (g) (kcal)
Cyclinex-2 65 g 0 9.8 286
Pro-Phree 82 g 0 0.0 418
Food List Servings

Fats 5 25 0.5 175
Fruits 5 125 3.5 325
Total per day 600 23.1 2,199

TABLE 22-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With Gyrate
Atrophy of the Choroid and Retina
Age Nutrient
1 2
ARG Protein Energy 2, 3 Fluid 4
Infants
0 to < 3 mo 40 - 35 2.20 - 1.25 150 - 125 160 - 130
3 to < 6 mo 35 - 33 2.00 - 1.15 140 - 120 160 - 130
6 to < 9 mo 33 - 30 1.80 - 1.05 130 - 115 145 - 125
9 to < 12 mo 30 - 25 1.60 - 0.90 120 - 110 135 - 120
(mg/kg) (g/day) (kcal/day) (mL/day)

Girls and Boys
1 to < 4 yr 25 - 23 8 - 13 945 - 1,890 945 - 1,890
4 to < 7 yr 23 - 20 12 - 15 1,365 - 2,415 1,365 - 2,415
7 to < 11 yr 20 - 18 14 - 17 1,730 - 3,465 1,730 - 3,465
Women
11 to < 15 yr 18 - 15 20 -23 1,575 - 3,150 1,575 - 3,150
15 to < 19 yr 15 - 13 20 - 23 1,260 - 3,150 1,260 - 3,150
≥ 19 yr 15 - 13 22 - 25 1,785 - 2,625 1,785 - 2,625
Men
11 to < 15 yr 18 - 15 20 - 23 2,100 - 3,885 2,100 - 3,885
15 to < 19 yr 15 - 13 21 - 24 2,200 - 4,095 2,200 - 4,095
≥ 19 yr 15 - 13 23 - 32 2,625 - 3,465 2,625 - 3,465
1
Recommended ARG intakes are estimates of requirements. ARG is an essential amino acid. Modify prescription
based on frequently obtained blood and/or plasma values and growth in infants and children and frequently
obtained plasma values and weight maintenance in adults.
2
Modified from references 9 and 10.
3
Energy intakes may be greater than normal when using L-amino acids for protein (34).
4
Modified from reference (5). Under normal circumstances, offer minimum of 1.5 mL fluid to neonates and 1.0 mL to
TABLE 22-2. Serving Lists for ARG-Restricted Diets: Average Nutrient Content per Serving
Food List Nutrient

ARG Protein Energy
(mg) (g) (kcal)
Breads/Cereals 45 0.9 50
Fats 5 0.1 35
1
Fruits 25 0.7 65
Vegetables 25 0.5 20
2
Alimentum ® Protein Hydrolysate Formula With Iron, Ready to Feed, 100 mL 77 1.86 68
2
Isomil ® Soy Formula With Iron, Ready to Feed, 100 mL 122 1.66 68
Pro-Phree ® Protein-Free Energy Module With Iron, Vitamins & Minerals, 100 mL 0 0.00 510
2

1
Watermelon contains large amounts of citrulline, a precursor of ARG (17).
2
3
TABLE 22-3. Serving Lists for ARG-Restricted Diets: Gerber ® Baby Foods (Beikost) 1
Food Weight Approximate ARG Protein Energy

(g) Measure (mg) (g) (kcal)
BREADS AND CEREAL
Baked Finger Snacks, Graduates ™

Animal crackers, cinnamon graham 20 5 crackers 45 1.5 83
Apple cinnamon cookies 24 2-1/2 cookies 45 1.4 106
Banana cookies 20 2-1/2 cookies 45 1.4 84
Strawberry fruit bars 20 2 bars 45 1.1 83
Veggie crackers 19 19 crackers 45 1.6 89
Cereals, Dry
Barley 7 1 Tbsp + 2-3/4 tsp 45 0.9 28
Mixed 10 2 Tbsp + 2 tsp 45 1.0 39
Oatmeal 5 4 tsp 45 0.7 19
Oatmeal/banana 6 4-1/2 tsp 45 0.6 23
Oatmeal/mixed fruit 7 5-3/4 tsp 45 0.8 29
Rice 7 5-3/4 tsp 45 0.6 27
Rice/apples 11 3 Tbsp 45 0.6 43
Rice/apple bits 9 7-1/4 tsp 45 0.6 36
Rice/bananas 9 7-1/4 tsp 45 0.7 36
Rice/mixed fruit 6 5 tsp 45 0.4 23
Cereals, Jarred
2nd Foods ®
Mixed/applesauce/banana 79 5-1/2 Tbsp 45 0.8 66
Oatmeal/applesauce/banana 64 4-1/2 Tbsp 45 0.8 53
Rice/applesauce 90 6-1/4 Tbsp 45 0.7 82
3rd Foods ®
Mixed/apples/banana 75 5-1/4 Tbsp 45 0.9 57
Oatmeal/apples/cinnamon 69 4-3/4 Tbsp 45 0.8 46
Vegetables
1st Foods ®
peas 7 1/2 Tbsp 25 0.2 3
potatoes 48 3-1/2 Tbsp 25 0.5 23
sweet potatoes 81 5-3/4 Tbsp 25 0.9 53
2nd Foods ®
creamed corn 36 2-1/2 Tbsp 25 0.6 22
creamed spinach 17 1-1/4 Tbsp 25 0.5 8
garden vegetables 14 1 Tbsp 25 0.3 5
peas 7 1/2 Tbsp 25 0.2 4
sweet Potatoes 83 5-3/4 Tbsp 25 0.8 52
3rd Foods ®
peas/rice 10 2 tsp 25 0.2 5
sweet potatoes 63 4-1/4 Tbsp 25 0.6 34
Tender Harvest ™
butternut squash/corn 21 ND 45 0.4 10
garden carrots/brown rice 42 ND 45 0.4 18
greenbean/potato 28 ND 25 0.6 18
spring garden vegetable 24 ND 25 0.3 8
FRUITS/JUICES
1st Foods ®
bananas 50 3-1/2 Tbsp 25 0.6 50
peaches 125 8-3/4 Tbsp 25 0.9 54
prunes 125 8-3/4 Tbsp 25 1.3 126

bananas 50 3-1/2 Tbsp 25 0.6 45
bananas/apples/pears 62 4-1/4 Tbsp 25 0.6 52
banana/pineapple 62 4-1/4 Tbsp 25 0.5 46
banana/strawberry 62 4-1/4 Tbsp 25 0.6 59
Hawaiian delight dessert - 2nd Foods ® 50 3-1/2 Tbsp 25 0.7 43
Hawaiian delight dessert - 3rd Foods ® 50 3-1/2 Tbsp 25 0.7 44
peach cobbler dessert 25 1-3/4 Tbsp 25 0.1 19
peaches - 2nd Foods ® 125 1/2 c + 2 tsp 25 0.9 80
peaches - 3rd Foods ® 63 1/4 c + 1/4 Tbsp 25 0.4 40
Fruit Dices, Graduates ™

Apples 83 ND 25 0.1 40
Mixed fruit 83 ND 25 0.3 40
Peaches 63 ND 25 0.3 31
Pears 63 ND 25 0.2 54
Fruit/Vegetable, Tender Harvest ™

Banana/oatmeal/peach 50 ND 25 0.6 37
Pear/winter squash 25 ND 25 0.3 13
Tropical fruit blend 125 ND 25 0.8 92
VEGETABLES
1st Foods ®
carrots 83 5-3/4 Tbsp 25 0.8 29
green beans 42 3 Tbsp 25 0.5 13
squash 36 2-1/2 Tbsp 25 0.3 12
2nd Foods ®
carrots 83 5-3/4 Tbsp 25 0.7 25
green beans 50 3-1/2 Tbsp 25 0.7 14
mixed vegetables 100 1-3/4 Tbsp 25 0.3 9
squash 63 4-1/4 Tbsp 25 0.5 20
3rd Foods ®
carrots 83 5-3/4 Tbsp 25 0.7 24
green beans/rice 42 3 Tbsp 25 0.5 18
squash 83 5-3/4 Tbsp 25 0.7 28
Vegetable Dices, Graduates ™

Carrots 63 ND 25 0.4 14
Green beans 36 ND 25 0.4 9
FREE FOODS A
Apple juice 167 5-3/4 oz 5 0.2 77

Apple/banana juice 167 5-3/4 oz 5 0.2 85
Apple/carrot juice 50 1-3/4 oz 5 0.1 21.5
Apple/cherry juice 167 5-3/4 oz 5 0.2 80
Apple/cranberry juice 167 5-3/4 oz 5 0.2 73
Apple/grape juice 167 5-3/4 oz 5 0.2 80
Apple/prune juice 167 5-3/4 oz 5 0.2 88
Apple/sweet potato juice 63 4-2/3 Tbsp 5 0.2 36
Mango/banana/passion fruit juice 50 1-3/4 oz 5 0.1 36
Mixed fruit juice 500 17 oz 5 0.5 240
Orange juice 50 1-3/4 oz 5 0.3 24
Pear juice 125 4-1/4 oz 5 0.2 59
Desserts
Fruit medley tropical fruit dessert* 50 3-1/2 Tbsp 5 0.1 32

Guava tropical fruit dessert* 50 3-1/2 Tbsp 5 0.1 35
Mango tropical fruit dessert* 50 3-1/2 Tbsp 5 0.1 37
Papaya tropical fruit dessert * 50 3-1/2 Tbsp 5 0.1 32
1st & 2nd Foods ®
applesauce 50 3-1/2 Tbsp 5 0.1 28
apple/blueberry 50 3-1/2 Tbsp 5 0.1 25
pears 50 3-1/2 Tbsp 5 0.2 28
3rd Foods ®
applesauce/apricot 50 3-1/2 Tbsp 5 0.2 52
apricots/mixed fruit 50 3-1/2 Tbsp 5 1.5 150
Fruit salad 50 3-1/2 Tbsp 5 0.2 32
Pear/pineapple 50 3-1/2 Tbsp 5 0.3 185
Pears 50 3-1/2 Tbsp 5 0.3 37
Plums/apples, 2nd Foods ® 50 3-1/2 Tbsp 5 0.2 35
Plums/apples, 3rd Foods ® 50 3-1/2 Tbsp 5 0.2 34
Prunes/apples 50 3-1/2 Tbsp 5 0.3 38
Tender Harvest ™
Pear/wild blueberry 50 3-1/2 Tbsp 5 0.2 30
Beverages
Graduates ™
Berry punch 500 17 oz 5 0.5 255
Fruit punch 167 5-3/4 oz 5 0.2 87
Tender Harvest
Apple/mango/kiwi 167 ND 5 0.2 100
Apple/strawberry 125 ND 5 0.2 75
1
ND = No data.

Level Level
1 tsp = 1/3rd Tbsp = 4.8 g
1 Tbsp = 1/16th cup = 14.3 g
1/4 cup = 4 Tbsp = 57.2 g
1/3 cup = 5-1/3rd Tbsp = 76.2 g
1/2 cup = 8 Tbsp = 114.3 g
2/3 cup = 10 2/3rd Tbsp = 152.5 g
3/4 cup = 12 Tbsp = 171.5 g
1 cup = 16 Tbsp = 228.6 g

1
TABLE 22-3. Serving Lists for ARG-Restricted Diets: Table Foods

BREADS AND CEREALS

Cream of Rice 61 1/4 cup 44 0.5 32
Cream of Wheat
instant 56 3 Tbsp + 2 tsp 44 1.0 36
Mix'n Eat
flavored 61 1/3 packet 45 1.0 54
plain 48 1/3 packet 41 1.3 49
quick 65 4 Tbsp + 1 tsp 43 1.0 35
regular 60 1/4 cup 48 1.1 39
Farina ® 73 1/4 cup + 1 Tbsp 42 1.0 36
Grits 91 1/4 cup + 2 Tbsp 43 1.3 54
Malt-o-Meal ® 75 1/4 cup + 1 Tbsp 46 1.1 38
Oats, regular, quick, instant 23 1 Tbsp + 1-1/2 tsp 44 0.6 14
Wheatena ® 46 3 Tbsp 42 0.9 26

All Bran ® 5 1 Tbsp + 3/4 tsp 45 0.6 14
Alpha-Bits ® 9 1/4 cup + 1 t 45 0.7 35
Apple Jacks ® 19 2/3 cup 49 1.0 72
Bran Buds ® 4 2-1/2 cups 43 0.6 11
Bran Chex ® 8 2 Tbsp + 2 tsp 44 0.9 26
40% Bran Flakes ® (Post) 7 2 Tbsp + 1 tsp 46 0.8 22
Cap'n Crunch ® 18 1/2 cup 44 0.9 78
Cap'n Crunch's ® Crunch Berries 18 1/2 cup 42 0.9 74
Cap'n Crunch's ® Peanut Butter 8 3 Tbsp + 1-3/4 tsp 45 0.6 34
Cheerios ® 4 3 Tbsp 48 0.6 17
Cinnamon Toast Crunch ® 33 3/4 cup + 2 Tbsp 43 1.2 140
Cocoa Krispies ® 11 1/4 cup + 1 Tbsp 46 0.6 43
Cocoa Pebbles ® 12 1/4 cup + 2 Tbsp 46 0.6 50
Cocoa Puffs ® 5 1-1/4 cups 43 1.2 138
Cookie Crisp ® 15 1/2 cup 45 0.8 60
Corn Bran ® 13 1/4 cup + 2 Tbsp 43 0.9 47
Corn Chex ® 19 2/3 cup 44 1.3 73
Corn Flakes ® 17 3/4 cup 45 1.4 66
Crispy Wheat'n Raisins ® 13 1/4 cup + 1 Tbsp 42 0.9 46
C W Post ®
plain 7 1 Tbsp + 1/4 tsp 43 0.6 29
w/ raisins 7 1 Tbsp + 1/4 tsp 43 0.6 31
Froot Loops ® 14 1/4 cup + 3 Tbsp 41 0.8 56
Frosted Mini-Wheats ® 8 1 piece 43 0.8 29
Frosted Rice Krinkles 11 1/3 cup 42 0.5 41
Frosted Rice Krispies ® 11 1/3 cup 42 0.5 41
Fruit Wheat Squares 18 3 Tbsp + 1-1/2 tsp 46 1.2 62
Fruity Pebbles ® 14 1/4 cup + 3 Tbsp 47 0.6 57
Golden Grahams ® 20 1/2 cup 43 1.1 75
Grape Nuts ® 7 1 Tbsp 42 0.8 25
Grape Nut Flakes ® 8 1/4 cup 44 0.9 29
Heartland ®, plain 7 1 Tbsp 42 0.7 31
Honey Nut Cheerios ® 5 2 Tbsp + 3/4 tsp 45 0.6 20
Honey Nut Corn Flakes ® 9 1/4 cup 46 0.6 38
Honeycomb ® 16 3/4 cup 44 1.0 64
King Vitaman ® 18 3/4 cup + 2 Tbsp 44 1.0 75
Kix ® 12 1/2 cup + 2 Tbsp 47 1.1 46

Life ® 3 1 Tbsp + 1/2 tsp 45 0.6 26
Lucky Charms ® 7 3 Tbsp + 1 tsp 45 0.6 26
Nutri-Grain ®
corn 16 1/4 cup + 5 tsp 42 1.3 60
rye 10 1/4 cup 43 0.9 36
wheat 11 1/4 cup 46 1.0 40
Oat Flakes 4 1 Tbsp + 3/4 tsp 45 0.7 14
Product 19 ® 12 1/4 cup + 2 Tbsp 43 1.2 47
Quisp ® 20 2/3 cup 46 1.0 82
Raisin Bran ®(Post) 9 2 Tbsp + 2 tsp 45 0.9 29
Rice Chex ® 9 1/4 cup + 2 Tbsp 41 0.5 37
Rice Krispies ® 8 1/4 cup + 1-1/2 tsp 45 0.5 32
Rice, puffed 9 2/3 cup 48 0.6 37
Special K ® 3 1 Tbsp + 2-1/2 tsp 45 0.6 13
Sugar Frosted Flakes ® 26 3/4 cup 43 1.3 100
Sugar Pops ® 28 1 cup 47 1.4 108
Sugar Smacks ® 12 1/3 cup 42 0.9 47
Super Sugar Crisp ® 14 1/4 cup + 3 Tbsp 45 0.9 54
Team ® 11 1/4 cup 47 0.7 41
Total ® 8 1/4 cup 43 0.8 29
Trix ® 21 3/4 cup 48 1.1 81
Wheat
puffed 6 1/2 cup 42 0.9 22
shredded 8 2 Tbsp + 1/2 tsp 43 0.8 27
Wheat Chex ® 9 3 Tbsp 42 0.9 32
Wheaties ® 9 1/4 cup + 1 Tbsp 45 0.9 32
Grains
Corn
cob, medium ear 32 1/2 ear 40 1.0 29
cooked
cream style 4 1/4 cup 45 1.1 33
whole kernel 31 3 Tbsp 42 1.0
Rice, prepared
brown 26 2 Tbsp + 1 tsp 45 0.6 30
fried 20 1 Tbsp + 1 tsp 44 0.8 30
Rice-A-Roni ® 26 1 Tbsp + 2 tsp 43 0.8 33
pilaf 20 1 Tbsp + 1 tsp 44 0.8 30
Spanish 30 2 Tbsp 41 0.5 26
white
instant 22 2 Tbsp 42 0.5 24
regular 26 2 Tbsp 46 0.5 28
Pasta, Cooked
Macaroni 22 2 Tbsp + 2 tsp 44 1.1 32
Noodles, egg 27 2 Tbsp + 2 tsp 44 1.1 33
Ramen ® noodles 20 2 Tbsp 41 1.1 45
spaghetti 21 2 Tbsp + 1 tsp 43 1.1 32
Tubers
Potatoes, sweet
baked
no skin, mashed 62 3 Tbsp 47 1.0 65
w/ skin, mashed 56 1/4 cup + 1-1/2 tsp 45 1.0 58
canned, packed in syrup 110 1/2 cup + 1 Tbsp 44 1.0 151
Potatoes, white
baked, no skin 40 1/3 cup 42 0.9 43
boiled

no skin 59 1/4 cup + 2 Tbsp 46 1.0 50
w/ skin 49 1/4 cup + 1 Tbsp 42 0.9 42
canned 20 2 potatoes 46 1.0 42
French fries (1/2" x 1/2" x 2"), 25 5 pieces 48 1.0 79
hash browns, frozen, cooked 29 3 Tbsp 44 0.9 64
Tater Tots ® 47 5 pieces 45 1.0 77
Yams, baked or boiled, mashed 34 1/4 cup 42 0.5 39
Miscellaneous
Chocolate sauce (Hershey's ®) 51 2-3/4 Tbsp 46 2.4 249
Chow Mein noodles 11 3 Tbsp 43 1.1 56
Jell-O ®, prepared w/ sugar 35 2 Tbsp + 1 tsp 46 0.5 21
Succotash 4 1 Tbsp 34 0.6 14
Snack Foods
Barnum's Animal Crackers ® 17 6-1/2 crackers 45 1.1 73
Cookies
chocolate chip 18 1-1/2 cookies 45 1.0 93
fig bar 28 1-3/4 bars 44 1.1 100
gingersnap 21 3 cookies 47 1.2 88
oatmeal raisin 11 3/4 cookie 42 0.7 48
Oreo ® 22 2 cookies 41 1.1 107
sandwich 22 2 cookies 43 1.1 109
Sno Balls ® 43 1 cookie 48 1.3 149
Social Tea Biscuits ® 21 4 biscuits 47 1.2 96
Sugar (butter) 20 1-1/2 cookie 47 1.2 83
Sugar Wafers ® (Nabisco) 30 5-1/2 cookies 45 1.2 147
vanilla wafer 20 5 cookies 44 1.1 92
Crackers
graham (2" x 2") 14 2 crackers 45 1.1 54
Melba toast 9 1-1/2 pieces 45 1.2 31
Ritz ® 17 5 crackers 43 1.2 83
Ritz Bits ®, cheese 11 16 crackers 44 1.1 55
Rykrisp ® 9 1-1/2 pieces 47 1.0 34
saltines 12 4 crackers 44 1.1 52
Triscuits ® 14 3 crackers 45 1.2 79
Waverly ® 16 2-1/4 crackers 44 1.2 78
Wheat Thins ® 16 9 crackers 46 1.2 78
Ding Dongs ® 36 3/4 cake 41 1.1 164
Doodads ®, original 8 2 Tbsp + 1 tsp 47 0.9 41
Doritos ®, plain 16 9 chips 43 1.2 79
Doughnut, cake 23 1/2 doughnut 43 1.1 90
Fritos ® 22 11 chips 46 1.5 120
Ho Hos ® 28 1 roll 48 1.1 119
Ice cream cone, wafer type 11 2 (cones only) 44 1.1 41
Popcorn
buttered 13 1-1/2 cups 45 1.3 6
caramel 10 1-3/4 cups 44 1.3 40
plain 10 1-3/4 cups 44 1.3 40
Potato chips (2" diameter) 14 7 chips 41 0.9 73
Pretzels 18 3 pretzles 42 1.8 70
Raisins, chocolate covered 13 10 raisins 25 0.7 55
Rice cakes 6 2/3 cake 43 0.5 23
Tortillas (6" diameter)
corn 18 3/4 piece 46 0.9 26
flour 15 1/2 piece 46 1.2 48
Twinkies ® 32 3/4 roll 40 1.0 115

FATS
Butter
stick 14 1 Tbsp 4 0.1 101
whipped 16 1 Tbsp + 2 tsp 5 0.1 113
Gravy
mushroom, canned 12 2-1/2 tsp 6 0.2 6
mushroom, dry 1 2 tsp 4 0.1 3
onion, dry 1 1 Tbsp 5 0.1 5
Margarine
imitation 27 1 Tbsp + 2-1/2 tsp 5 0.1 92
soft 19 1 Tbsp + 1 tsp 5 0.2 135
stick or brick 15 1 Tbsp + 1/4 tsp 5 0.1 110
liquid 6 1-1/4 tsp 5 0.1 8
powder 2 1-1/4 tsp 5 0.1 13
Rich's ® Coffee Rich 24 1 Tbsp + 2 tsp 5 0.1 37
Polyrich ® 24 2 Tbsp + 2 tsp 5 0.1 37
Olives
black 5 1 olive 6 0.1 9
green 4 3/4 olive 5 0.1 4
French 12 2-1/4 tsp 5 0.1 50
Italian 10 2 tsp 5 0.1 46
mayonnaise 7 1-1/2 tsp 5 0.1 49
Miracle Whip ® 16 1 Tbsp + 1/2 tsp 5 0.1 82
ranch 5 1 tsp 6 0.1 26
Russian 4 3/4 tsp 4 0.1 19
Thousand Island 8 1-1/2 tsp 5 0.1 29
Tartar sauce 6 1-1/4 tsp 5 0.1 31
Cool Whip ®
extra creamy 5 1 Tbsp 4 0.1 15
regular 9 2 Tbsp + 1 tsp 5 0.1 26
Dessert toppings w/ sodium caseinate, pressurized 13 3 Tbsp 5 0.1 34
Richwhip ®
pressurized 12 1 Tbsp + 2 tsp 5 0.1 34
prewhipped 6 1 Tbsp + 1-1/2 tsp 6 0.1 18
Whipped cream, pressurized 4 1 Tbsp + 1/2 tsp 5 0.1 11
FRUITS.
Apricots
canned, heavy syrup 129 1/2 cup 27 0.7 107
dried
cooked, mashed 47 3 Tbsp 23 0.6 40
uncooked, halves 18 5 halves 25 0.6 42
frozen, sweetened 121 1/2 cup 27 0.9 119
nectar, canned 157 5 fl oz 24 0.6 88
sliced 51 1/3 23 0.7 25
Avocadoes, all varieties, mashed 43 3 Tbsp 26 0.9 69
Bananas, sliced 56 1/4 cup 26 0.6 52
Blackberries
canned, heavy syrup 48 3 Tbsp 26 0.6 44
raw 72 1/2 cup 22 0.5 38

Blueberries
raw 72 1/2 cup 25 0.5 41
Cherries canned, heavy syrup
sour, red, 175 3/4 cup 21 1.3 160
sweet 127 3/4 cup + 2 Tbsp 24 1.5 91
Coconut, dried, sweetened 5 1 Tbsp 26 0.2 23
Currants, black, raw 35 1/4 cup + 1 Tbsp 25 0.5 22
Dates 33 4 dates 22 0.7 91
Figs
canned, heavy syrup 259 1 cup 23 1.0 228
dried
cooked, mashed 85 1/3 cup 26 1.1 92
uncooked, chopped 37 3 Tbsp 26 1.1 95
whole, medium 150 3 fruits 27 1.1 111
Fruit cocktail, canned, heavy syrup 168 2/3 cup 27 0.7 123
Gooseberries, canned, light syrup 79 1/4 cup + 1 Tbsp 25 0.5 57
canned, light syrup 63 1/4 cup 25 0.4 38
juice, canned, unsweetened 77 2-1/2 fl oz 27 0.4 29
sections 57 1/4 cup 25 0.4 18
Grapes
adherent skin 50 1/4 cup + 1 Tbsp 25 0.3 35
juice, canned 47 1-1/2 fl oz 22 0.3 29
slipskin 124 3/4 cup 26 1.0 63
Thompson, seedless, canned, heavy syrup 64 1/4 cup 22 0.3 47
Guavas 124 3/4 cup 26 1.0 63
Kiwi fruit 95 1-1/4 fruits 25 0.9 58
Lemons 33 1/2 fruit 25 0.4 9
Mangoes, sliced 124 3/4 cup 23 0.6 81
Melons, cubed
cantaloupe 40 1/4 cup 22 0.4 14
honeydew 85 1/2 cup 25 0.4 30
Nectarines 103 3/4 cup 25 1.0 51
Oranges
juice
canned 54 1-3/4 fl oz 24 0.4 24
frozen, diluted 34 3 Tbsp 22 0.3 16
sections 245 1-3/4 cups 25 1.5 95
Papayas
Peaches
canned, heavy syrup, sliced
dried
cooked, mashed 89 1/3 cup 25 1.0 56
uncooked, halves 26 2 24 0.9 62
sliced 127 3/4 cup 23 0.9 55
Persimmons, Japanese 84 1/2 fruit 21 0.5 59
Pineapple
cubed 136 3/4 cup + 2 Tbsp 24 0.5 66
tidbits, crushed 64 3/4 cup 23 0.7 149
Plantains, cooked, sliced 38 1/4 cup 25 0.3 45
Plums
sliced 198 3 plums 26 1.6 109
Raisins
golden 9 1 Tbsp 23 0.3 27

seedless 11 1 Tbsp + 1/2 tsp 25 0.3 32
Raspberries
frozen, red, sweetened 94 1/4 cup + 2 Tbsp 27 0.7 97
raw 61 1/2 cup 23 0.6 30
frozen, sweetened 112 1/4 cup + 3 Tbsp 26 0.6 107
raw 61 1/4 cup + 1 Tbsp 27 0.4 27
Tangerines
canned, w/ light syrup 84 1/3 cup 26 0.4 51
juice, canned 62 2 fl oz 22 0.3 32
sections 61 1/4 cup + 1 Tbsp 27 0.4 27
VEGETABLES
Asparagus
fresh or frozen, cooked 20 1-1/3 spears 24 0.5 5
raw 17 2 Tbsp 24 0.5 4
Bamboo shoots, canned, sliced 40 1/3 cup 23 0.6 5
Beans
snap green, cooked
fresh or canned 31 1/4 cup 24 0.6 11
frozen 45 1/3 cup 25 0.6 12
mung, seed attached to sprout, cooked 16 2 Tbsp 23 0.3 3
yellow wax, canned 54 3 Tbsp + 1 tsp 25 0.6 11
Beets
greens, cooked, chopped 36 1/4 cup 26 0.9 10
red, sliced
fresh, canned, cooked 85 1/2 cup 24 0.9 26
pickled 114 1/2 cup 24` 0.9 75
cooked 16 1 Tbsp + 2 tsp 25 0.5 5
raw 17 3 Tbsp 24 0.5 5
Brussels sprouts, fresh or frozen, cooked 16 3/4 sprout 24 0.4 6
Cabbage, shredded
Chinese (Pak-choi)
cooked 28 2 Tbsp + 2 tsp 25 0.4 3
raw 31 1/4 cup + 3 Tbsp 26 0.5 4
red
cooked 37 1/4 cup 23 0.4 8
raw 31 1/4 cup + 3 Tbsp 24 0.4 8
white
cooked 47 1/4 cup + 1 Tbsp 25 0.4 10
raw 35 1/2 cup 24 0.4 8
Carrots, sliced
canned 91 1/2 cup + 2 Tbsp 24 0.6 21
cooked 52 1/3 cup 23 0.6 23
raw 55 1/2 cup 24 0.6 24
Cauliflower
fresh, cooked 27 3 Tbsp + 1-1/2 tsp 24 0.5 7
frozen, cooked 52 1/3 cup 23 0.6 6
raw 25 1/4 cup 24 0.5 6
Celery, diced
cooked 150 1 cup 23 0.6 22
raw 120 1 cup 24 0.8 19
Chard, Swiss, cooked 22 2 Tbsp 27 0.4 5
Chayote fruit, cooked 80 1/2 cup 21 0.5 19

fresh 22 1/4 cup 27 0.4 5
frozen 15 1 Tbsp + 1 tsp 27 0.4 5
Eggplant, cubed
cooked 78 1/2 cup + 1 Tbsp 27 0.4 10
raw 54 1/2 cup 25 0.4 15
Endive, raw, shredded 41 3/4 cup 25 0.5 11
Kale, cooked
fresh 37 3 Tbsp 23 0.5 6
frozen 16 2 Tbsp 26 0.5 5
Kohlrabi, sliced
cooked 24 2 Tbsp 26 0.5 8
raw 26 3 Tbsp 27 0.4 7
Leeks, diced
cooked 21 1/2 cup 23 0.4 6
raw 52 1/4 cup + 1 tsp 22 0.4 16
Lettuce, shredded
bibb and Boston 37 2/3 cup 26 0.5 5
iceberg 42 3/4 cup 27 0.4 5
leaf 37 1/2 cup + 2 T 27 0.5 7
Romaine and cos 28 1/2 cup 25 0.5 4
Mushrooms
Agaricus bisporus
cooked or canned 24 2 mushrooms 23 0.5 6
raw, diced 22 1/4 cup + 1 Tbsp 23 0.5 5
Shitake
cooked, pieces 27 3 Tbsp 24 0.4 15
dried 4 1 mushroom 26 0.4 12
Mustard greens, fresh or frozen, chopped
cooked 15 1 Tbsp + 2 tsp 24 0.3 2
raw 13 3 Tbsp + 2 tsp 25 0.3 3
Okra, cooked 30 3 Tbsp 23
Onions
cooked 20 1 Tbsp + 1-1/2 tsp 24 0.2 6
raw, diced 17 1 Tbsp + 2 tsp 26 0.2 6
rings, canned 26 1/2 cup 25 0.4 92
Parsnips, cooked 78 1/2 cup 27 1.0 63
Peas
green
canned or frozen 6 1-3/4 tsp 25 0.3 5
w/ carrots 10 1 Tbsp 23 0.3 5
pods (edible)
cooked 15 1 Tbsp + 1-1/2 tsp 24 0.5 6
raw 18 2 Tbsp 24 0.5 8
Peppers, green, sweet, diced
cooked 76 1/2 cup + 1 Tbsp 23 0.5 14
raw 56 1/2 cup + 1 Tbsp 233 0.5 14
Pickles
dill
relish 56 1/4 cup 25 0.4 11
whole, small 60 1 pickle 26 0.4 7
sweet
relish 83 1/3 cup 27 0.4 114
sliced 60 2 pieces 26 0.4 88
Pumpkin, canned 46 3 Tbsp 27 0.5 16
Radishes, sliced
red 58 1/2 cup 23 0.3 10
white icicle 33 1/3 cup 21 0.4 5

Rutabagas
cooked, mashed 18 1 Tbsp + 2 tsp 24 0.2 6
cubed 18 2 Tbsp 26 0.2 6
Sauerkraut 49 3 Tbsp + 1 tsp 25 0.4 9
Shallots, chopped 13 1 Tbsp + 1 tsp 24 0.3 10
Spinach, chopped
fresh or frozen, cooked 15 1 Tbsp 8 1 tsp 24 0.4 3
raw 14 1/4 cup 23 0.4 3
fresh or frozen, cooked 67 1/4 cup + 2 Tbsp 26 0.6 13
raw, sliced 49 1/4 cup + 2 Tbsp 24 0.6 10
Squash, winter
acorn, baked, cubed 38 3 Tbsp 24 0.4 22
butternut
baked, cubed 51 1/4 cup 26 0.5 21
boiled, mashed 35 2 Tbsp + 2 tsp 24 0.4 14
Hubbard
baked, cubed 29 1/4 cup 24 0.7 14
boiled, mashed 30 2 Tbsp 25 0.4 9
spaghetti, boiled 98 1/2 cup + 2 Tbsp 25 0.6 29
Taro, cooked
leaves 19 2 Tbsp 23 0.5 5
root, sliced 66 1/2 cup 24 0.3 94
Tomatoes
catsup 62 1/4 cup 26 1.2 66
fresh
cooked 90 1/4 cup + 2 Tbsp 24 1.0 23
chopped 119 2/3 cup 26 1.1 23
juice 153 5 fl oz 23 1.2 26
paste 33 2 Tbsp 25 1.2 28
purée 78 1/4 cup + 1 Tbsp 26 1.3 32
sauce
marinara 92 1/4 cup + 2 Tbsp 25 1.2 27
spaghetti 62 1/4 cup 22 1.1 68
w/ onions, green peppers, and celery 61 1/4 cup 23 0.6 25
stewed, canned 112 1/4 cup + 3 Tbsp 25 1.0 29
Turnips
greens, cooked, chopped 36 1/4 cup 26 0.4 7
root, diced
cooked 127 3/4 cup + 1 Tbsp 24 0.9 23
raw 98 3/4 cup 23 0.9 26
Vegetable cocktail juice (V8 ®) 212 7 fl oz 25 1.3 40
Vegetables, mixed
canned 12 1 Tbsp + 1/4 tsp 24 0.4 7
frozen, cooked 12 1 Tbsp 23 0.3 7
Watercress 17 1/2 cup 26 0.4 2
Asparagus, Cream of 37 2 Tbsp + 1 tsp 25 0.7 25
Celery, Cream of 47 3 Tbsp 22 0.6 34
Minestrone 15 1 Tbsp 25 0.5 10
Mushroom, Cream of 37 2 Tbsp + 1 tsp 25 0.6 38
Onion 6 1-1/4 tsp 26 0.2 3
Potato, Cream of 42 2 Tbsp + 2 tsp 25 0.6 25
Scotch broth 13 2-1/2 tsp 24 0.5 8
Tomato 47 3 Tbsp 23 0.8 32
Tomato Bisque 47 3 Tbsp 24 0.8 45
Tomato Rice 48 3 Tbsp 23 0.8 45

Vegetable 31 2 Tbsp 25 0.5 18
Vegetable, Old Fashioned 31 2 Tbsp 25 0.8 45
Vegetable, Chunky, Ready To Serve 30 2 Tbsp 24 0.4 15
FREE FOODS A
Beverages
Chocolate drink powder (Quik ®) 3 1 tsp 5 0.1 11
Fruit juice
Cranberry cocktail 253 8 fl oz 5 0.1 144
Fruit drink 78 2-1/2 fl oz 5 0.1 39
Lemon 15 1/2 fl oz 4 0.1 3
Lime 31 1 fl oz 5 0.1 6
Pineapple 63 2 fl oz 5 0.2 35
Prune 64 2 fl oz 7 0.4 46
Tangerine sweetened w/ sugar 16 1 Tbsp 5 0.1 8
Lemonade 92 3 fl oz 6 0.1 37
Nectar
Papaya 173 5-1/2 fl oz 5 0.3 98
Peach 78 2-1/2 fl oz 6 0.2 43
Pear 250 8 fl oz 4 0.3 150
Desserts
Apple butter 40 2 Tbsp 5 0.2 74
Fruit bars, frozen
orange 19 1/4 bar 5 0.1 18
pineapple 24 1/3 bar 4 0.1 23
Fruit ice 18 1 Tbsp + 1-1/2 tsp 5 0.1 23
Fruit Roll-Ups ® 14 1 piece 5 0.2 55
M & M's, plain 3 3-1/2 pieces 5 0.2 14
Mocha Mix, frozen
chocolate 4 1-1/2 tsp 4 0.1 8
vanilla 5 2 tsp 5 0.1 11
Sherbet, orange 12 1 Tbsp 5 0.1 17
Sorbet
peach 44 3 Tbsp 5 0.2 45
pineapple 30 2 Tbsp 5 0.1 29
strawberry 30 2 Tbsp 5 0.1 29
Fruit/Fruit Products
Apples
canned, w/ sugar 76 1/4 cup + 2 Tbsp 5 0.1 51
dried
raw 16 3 Tbsp 5 0.1 39
cooked 64 1/4 cup 5 0.1 36
raw, small 91 1/3 apple 6 0.2 54
sauce
sweetened w/ sugar 80 1/4 cup + 1 Tbsp 5 0.1 61
unsweetened 91 1/4 cup + 2 Tbsp 5 0.2 39
Cranberry sauce w/ sugar 80 1/4 cup + 1 Tbsp 5 0.1 51
Fruit juice bar 26 1/2 bar 4 0.0 22
Fruit salad, heavy syrup 53 3 Tbsp + 1 tsp 5 0.2 39
Fun fruits ® 77 3 pieces 5 0.3 300
Guava sauce 59 1/4 cup 5 0.2 21
Mixed fruit, heavy syrup 48 3 Tbsp 5 0.2 34
Pie filling
apple 184 3/4 cup 6 0.2 203
cherry 63 1/4 cup 5 0.3 65
peach 67 1/4 cup 5 0.2 71
strawberry 24 1 Tbsp + 1-1/2 tsp 5 0.1 29
Pears
canned, heavy syrup 160 1/2 cup + 2 Tbsp 5 0.3 118
dried
uncooked, halves 18 1 6 0.3 46
sliced 72 1/4 cup + 3 Tbsp 0.3 43
Plums, purple, canned, heavy syrup 86 1/3 cup 5 0.3 77
Prunes
canned, heavy syrup 37 2 Tbsp + 1-1/2 tsp 5 0.3 38
dried
uncooked, halves 13 1-1/2 5 0.3 30
Rhubarb, cooked, sweetened 45 3 Tbsp 5 0.2 52
Miscellaneous
Barbecue sauce 16 1 Tbsp 6 0.3 12
Chives 3 1 Tbsp 6 0.1 1
Frosting, chocolate 8 1-1/2 tsp 5 0.1 32
Goldfish ® crackers, original 2 3 crackers 5 0.1 10
Horseradish 12 2 tsp 5 0.1 1
Jalepeño peppers, sliced 17 2 Tbsp 7 0.1 4
Jams and preserves 20 1 Tbsp 5 0.1 54
Marmalade 13 2 tsp 5 0.1 33
FREE FOODS B
These foods contain little or no ARG. They may be used as desired if patient is not overweight and if they do not depress appetite for
prescribed foods.
Beverages
Apple juice 124 4 fl oz 1 0.1 58
cola 123 4 fl oz 0 0.0 50
cream soda 124 4 fl oz 0 0.0 63
Dr Pepper ® 123 4 fl oz 0 0.0 50
ginger ale 122 4 fl oz 0 0.0 41
grape soda 124 4 fl oz 0 0.0 53
lemon-lime soda 123 4 fl oz 0 0.0 49
orange soda 124 4 fl oz 0 0.0 60
root beer 123 4 fl oz 0 0.0 50
Beer
light 30 1 fl oz 2 0.1 8
regular 30 1 fl oz 3 0.1 12
Coffee
brewed 30 1 fl oz 0 0.0 1
instant powder 5 1 Tbsp 3 0.7 13
Exceed ® Energy Drink 124 4 fl oz 0 0.0 35
Fruit drink (Hi-cup ®) 124 4 fl oz 0 0.0 58
Gatorade ® Thirst Quencher 121 4 fl oz 0 0.0 30
Kool-Aid ®, sweetened w/ sugar 123 4 fl oz 0 0.0 49
Orange drink powder (Tang ®) 8 2 tsp 1 0.0 31
Strawberry drink powder (Quik ®) 8 1 Tbsp 0 0.0 33
Tea
brewed 30 1 fl oz 0 0.0 1
instant powder
sweetened 13 1 Tbsp 0 0.1 51
unsweetened 1 1 Tbsp 0 0.0 3

Desserts/Sweeteners
Candies
candy corn 16 10 pieces 1 0.0 58
gumdrops 4 2 pieces 0 0.0 14
hard candy 10 2 pieces 0 0.0 39
jelly beans 28 10 pieces 0 0.0 103
Frosting, strawberry and vanilla 16 1 Tbsp 0 0.0 69
Honey 21 1 Tbsp 1 0.1 64
Jellies 20 1 Tbsp 2 0.0 54
Lemon pudding (Hunts ®) 120 1 container 0 0.0 151
Molasses 21 1 Tbsp 0 0.0 48
Popsicle ® twin 128 1 pop 0 0.0 95
Sugar
brown 14 1 Tbsp 0 0.0 52
powdered 8 1 Tbsp 0 0.0 31
table 12 1 Tbsp 0 0.0 48
Syrup
corn 20 1 Tbsp 0 0.0 58
maple 20 1 Tbsp 0 0.0 50
table 20 1 Tbsp 0 0.0 50
Miscellaneous
Lard 13 1 Tbsp 0 0.0 115
Oil, olive or vegetable 14 1 Tbsp 0 0.0 120
Richwhip ® liquid 14 1 Tbsp 0 0.0 40
Salad dressing, oil/vinegar 16 1 Tbsp 0 0.0 70
Shortening 13 1 Tbsp 0 0.0 113
1
For nutrient composition of very-low-protein foods, see Appendix 12, p A-11.

TABLE 22-4. Nutrient Composition of CYCLINEX ®-1 1, 3 and CYCLINEX ®-2 2, 3
Nutrient Cyclinex-1 Cyclinex-2

Energy, kcal 510 68 440 32
Protein equiv, g 7.50 1.000 15.00 1.000
Nitrogen, g 1.20 0.160 2.40 0.160
Amino acids, g 9.65 1.287 19.30 1.287
Cystine, g 0.30 0.040 0.60 0.040
Histidine, g 0.36 0.048 0.72 0.048
Isoleucine, g 1.28 0.170 2.56 0.170
Leucine, g 2.17 0.289 4.34 0.289
Lysine, g 1.11 0.148 2.22 0.148
Methionine, g 0.34 0.045 0.68 0.045
Phenylalanine, g 0.75 0.100 1.50 0.100
Threonine, g 0.75 0.100 1.50 0.100
Tryptophan, g 0.28 0.037 0.56 0.037
Tyrosine, g 0.88 0.117 1.76 0.117
Valine, g 1.43 0.190 2.86 0.190
L-Carnitine, mg 190 25.00 370 24.67
Taurine, mg 40 5.3 60 4.00
Carbohydrate, g 57.0 7.60 45.0 3.00
Fat, g 24.6 3.28 17.0 1.13
Linoleic acid, g 2.00 0.266 1.82 0.121
α-Linolenic acid, g 0.41 0.055 0.28 0.019
Minerals
Calcium, mg 650 86 1,150 77
Chloride, mg/mEq 390/11.00 52.0/1.47 1,325/37.37 88.3/2.49
Chromium, µg 12 1.60 37 2.47
Copper, mg 1.25 0.167 1.30 0.09
Iodine, µg 80 10.67 150 10
Iron, mg 10.0 1.33 17.0 1.13
Magnesium, mg 55 7.3 300 20.0
Manganese, mg 0.50 0.067 1.00 0.07
Phosphorus, mg 455 60 1,020 68
Potassium, mg/mEq 760/19.44 101/2.59 1,800/46.03 120/3.07
Selenium, µg 25 3.33 37 2.47
Sodium, mg/mEq 215/9.35 28.7/1.25 1,175/51.11 78.3/3.41
Zinc, mg 9.5 1.27 17.0 1.13
Vitamins
A, µg RE 480 64 908 61
D, µg 7.50 1.00 8.12 0.54
E, mg α-TE 11.40 1.52 16.11 1.10
K, µg 60 8.0 70 4.67
Ascorbic acid, mg 60 8 75 5
Biotin, µg 75 10 150 10
B6, mg 0.85 0.113 1.75 0.12
B12, µg 5.60 0.750 7.30 0.487
Choline, mg 100 13.3 130 8.7
Folate, µg 250 33.00 530 35.33
Inositol, mg 50 6.7 110 7.3
Niacin equiv, mg 16.70 2.23 30.3 2.02
Riboflavin, mg 1.0 0.133 2.4 0.160
Thiamin, mg 2.0 0.267 4.0 0.267
1 2
3
Approximate packed weight of Cyclinex-1 and Cyclinex-2 in level, dry US standard household measures:
Cyclinex-1 Cyclinex-2
1 Tbsp = 8g 8g
1/4 cup = 26 g 32 g
1/3 cup = 35 g 41 g
1/2 cup = 53 g 61 g
1 cup = 105 g 117 g

TABLE 22.5. Gyrate Atrophy Clinical Summary Sheet
Name: Hospital Number :

Mo Day Year

Length/ Weight Head Hgb Hct Ferritin Transthyretin Ammonia ARG ORN ARG Protein Energy
Height Circum
(mo/d/yr) (yrs/mo) (cm) (kg) (cm) (g/dL) (%) (ng/mL) (mg/dL) (µmol/L) (µmol/L) (µmol/L) (mg) (g) (kcal)
Gyrate Atrophy 403
REFERENCES
1. Armstrong MD, Stave U: A study of plasma free amino acid levels. II. Normal values for children and adults.
Metabolism 1973;22:561-569.
Dis 2000;23 Suppl 1:29A.
3. Bakker HD, Abeling NG, van Schooneveld MJ, et al: A far advanced case of gyrate atrophy in a 12-year-old girl.
4. Barbul A: Arginine: Biochemistry, physiology, and therapeutic implications. JPEN 1986;10:227-238.
1996.
6. Berson EL, Shih VE, Sullivan PL: Ocular findings in patients with gyrate atrophy on pyridoxine and low-protein,
low-arginine diets. Ophthalmology 1981;88:311-315.
7. Bell L, McInnes RR, Arshinoff SA, McCulloch JC: Dietary treatment of hyperornithinemia in gyrate atrophy. J Amer
Diet Assoc 1981;79:139-145.
8. Botschner J, Smth DW, Simell O, Scriver CR: Comparison of ornithine metabolism in hyperornithinemia-
hyperammonaemia-homocitrulluria syndrome, lysinuric protein intolerance, and gyrate atrophy fibroblasts. J
Inher Metab Dis 1989;12:33-40.
11. Goldblum OM, Brusilow SW, Maldonado YA, Farmer ER: Neonatal citrullinemia associated with cutaneous
manifestations and arginine deficiency. J Am Acad Dermatol 1986;14:321-326.
12. Gropper SS; Acosta PB: Effect of simultaneous ingestion of L-amino acids and whole protein on plasma amino
acid and urea nitrogen concentrations in humans. J Parenteral and Enteral Nutrition 1991;15:48-53.
13. Gropper SS; Gropper DM; Acosta PB. Plasma amino acid response to ingestion of L-amino acids and whole
14. Hayasaka S, Saito T, Nakajima H, et al: Gyrate atrophy with hyperornithinaemia: Different types of responsiveness
to vitamin B6. Brit J Ophthalmol 1981;65:478-483.
15. Heinanen K, Nanto-Salonen K, Leino L, et al: Gyrate atrophy of the choroid and retina: Lymphocyte ornithine-
delta-aminotransferase activity in different mutations and carriers. Pediatr Res 1998;44:381-385.
17. Inatomi H, Sasaki T, Suyama Y, Inukai F: Studies on nonprotein amino acids in plants. IV. Distribution of citrulline
in watermelon fruit. Bull Fac Agr , Meiji Univ 1969;24:23-29.
19. Kaiser-Kupfer MI, Caruso RC, Valle D: Gyrate atrophy of the choroid and retina. Long-term reduction of ornithine
slows retinal degeneration. Arch Ophthalmol 1991;109:1539-1548.
20. Kaiser-Kupfer MI, DeMonasterio FM, Valle D, et al: Gyrate atrophy of the choroid and retina. Improved visual
function following reduction of plasma ornithine by diet. Science 1980;210:1128-1131.
21. Kaiser-Kupfer MI, Valle D, Bron AJ: Clinical and biochemical heterogeneity in gyrate atrophy. Am J Ophthalmol.
1980;89:219-222.
22. Kaiser-Kupfer MI, Valle D, del Valle LA: A specific enzyme defect in gyrate atrophy. Am J Ophthalmol 1978;85:200-
204.
23. Kennaway NG, Stankova L, Wirtz MK, Weleber RG: Gyrate atrophy of the choroid and retina: Characterization of
mutant ornithine aminotransferase and mechanism of response to vitamin B6. Am J Hum Genet 1989;44:344-
352.
24. Kennaway NG, Weleber RG, Buist NR: Gyrate atrophy of the choroid and retina with hyperornithinemia:
Biochemical and histologic studies and response to vitamin B6. Am J Hum Genet 1980;32:529-541.
1982.
1987;1:1-17.
27. Mashima YG, Weleber RG, Kennaway NG, Inana G: Genotype-phenotype correlation of a pyridoxine-responsive
form of gyrate atrophy. Ophthalmic Genet 1999;20;219-224.
28. McInnes RR, Arshinoff SA, Bell L, et al: Hyperornithinemia and gyrate atrophy of the retina: Improvement of vision
during treatment with a low-arginine diet. Lancet 1981;1:513-517.
29. Meites S (ed): Pediatric Clinical Chemistry: Reference Normal Values, ed 3. Washington, DC: AAAC Press, 1989.
30. Milner JA, Visek WJ: Urinary metabolites characteristic of urea-cycle amino acid deficiency. Metabolism
1975;24:643-651.

31. Nanto-Salonen K, Komu M, Luudbom N, et al: Reduced brain creatine in gyrate atrophy of the choroid and retina
with hyperornithinemia. Neurology 1999;53;303-307.
32. O'Donnell JJ, Sandman RP, Martin SR: Gyrate atrophy of the retina: Inborn error of L-ornithine:2-oxoacid
aminotransferase. Science 1978;200:200-201.
1955;56:231-51.
35. Rose WC: The amino acid requirements of adult man. Nutr Abstr Rev 1975;27;631-647.
36. Schaumburg H, Kaplan J, Windebank A, et al: Sensory neuropathy from pyridoxine abuse. A new megavitamin
syndrome. N Engl J Med 1983;309:445-448.
nitrogen retention in patients with phenylketonuria. J Nutr Med 1994;4 :415-418.
38. Shih VE, Berson EL, Garguilo M: Reduction of hyperornithinemia with a low-protein, low-arginine diet and
pyridoxine in patients with a deficiency of ornithine-ketoacid transaminase (OKT) activity and gyrate atrophy of
the choroid and retina. Clin Chim Acta 1981;113:243-251.
39. Shih VE, Mandell R, Berson EL: Pyridoxine effects on ornithine ketoacid transaminase activity in fibroblasts from
carriers of two forms of gyrate atrophy of the choroid and retina. Am H Hum Genet 1988;43:929-933.
40. Shih VE, Stöckler-Ipsiroglu S: Disorders of ornithine and creatine metabolism. In Fernandes J, et al (eds): Inborn
Metabolic Diseases: Diagnosis and Treatment, ed 3. New York: Springer Verlag, 2000, pp 233-240.
41. Simell O, Takki K: Raised plasma ornithine and gyrate atrophy of the choroid and retina. Lancet
1973;1:1031-1033.
42. Sipila I, Simell O: Creatine corrects muscle 31P spectrum in gyrate atrophy with hyperornithinemia. Eur J Clin
Invest 1999;29:1060-1065.
1976.
synthetic amino acid formula - A controlled trial. N Engl J Med 1982;306(17):1013-1018.
1983;7:280-288.
1989;143:828-832.
47. Valle D, Simell O: The hyperornithinemias. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of
48. Valle D, Walser M, Brusilow SW, Kaiser-Kupfer M: Gyrate atrophy of the choroid and retina. Amino acid
metabolism and correction of hyperornithinemia with an arginine-deficient diet. J Clin Invest 1990;5:371-378.
49. Valle D, Walser M, Brusilow S, Kaiser-Kupfer MI, Takki K: Gyrate atrophy of the choroid and retina. Biochemical
considerations and experience with an arginine-restricted diet. Ophthalmology 1981;88:325-330.
50. Visek WJ: Arginine needs, physiological state and usual diets, a reevaluation. J Nutr 1986;116:36-46.
51. Weleber RG, Kennaway NG, Buist NR: Vitamin B6 in management of gyrate atrophy of choroid and retina. Lancet
1978;2:213.
52. Weleber RG, Wirtz MK, Kennaway NG: Gyrate atrophy of the choroid and retina: Clinical and biochemical
heterogeneity and response to vitamin B6. Birth Defects 1982;18:219-231.
53. Zieve L: Conditional deficiencies of ornithine and arginine. J Am Coll Nutr 1986;5:167-176.

PROTOCOL 23 — Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome

I. Introduction
Ornithine (ORN), an amino acid not used for protein synthesis, has several metabolic pathways. ORN is
used in synthesis of creatine, glutamate, proline, and polyamines and is important in the urea cycle.
The hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is believed to result from
a mitochondrial transport defect for ORN (9, 32, 33, 42). Plasma concentrations of ammonia, ORN,
glutamine, and alanine are often increased and lysine concentration may be decreased (42). Urinary
excretion of homocitrulline, polyamines, and orotic acid are increased many-fold above normal (32-
34).
Symptoms of HHH syndrome may appear in neonates, children, or adults. Periods of ataxia, lethargy,
vomiting, choreoathetosis, seizures, or coma coupled with delayed development may be some of the
presenting symptoms. Muscle hypotonia followed later by spasticity may occur. Some patients have
had a deficiency of-CoAgulation factors VII and X (7, 38). Prenatal diagnosis is available (6, 14).

Outcome appears to be dependent on extent of deficiency of ORN transporter protein, the subsequent
mitochondrial deficiency of ORN, the resulting hyperammonemia, and the age at which therapy
begins. Mitochondrial ORN is essential as a stimulator of carbamylphosphate synthetase (3, 4, 11,
45).

A. The Defect
1. Hyperornithinemia results from defect in:
a. Mitochondrial ORN transport protein (17, 20).
b. Ornithine-∆-aminotransferase (Protocol 22).
a. Poor feeding, vomiting, lethargy, hypotonia, spasticity, irritability, twitching, seizures,
apnea or coma (23, 27)
b. Developmental delay (23).
c. Plasma ammonia > 150 µmol/L in newborn period and > 80 µmol/L thereafter (23).
2. See references 6, 14, 23, 28, 33, and 34 for methods of diagnosis.
3. Other causes of inherited hyperammonemia must be ruled out, including the following:
a. Abnormalities of fatty acid metabolism (Protocol 20).
b. Defects of urea cycle enzymes (Protocol 24).
c. Lysinuric protein intolerance (Protocol 11).
d. Organic acidurias (Protocols 5, 6, 10, 13, 18, 20).
4. Causes of acquired hyperammonemia that must be ruled out include the following:
a. Deficient arginine (ARG) supply.
b. Reye's syndrome.
c. Transient hyperammonemia of newborn.
d. Valproate therapy.
Warning: Laboratory results MUST be available within 4 to 8 hours when disorder of
urea cycle enzyme is suspected as hyperammonemia is a metabolic
emergency.

1. Restrict dietary protein to amount tolerated without causing hyperammonemia (7, 9, 12, 30).
2. Prevent excessive body protein catabolism.
412 HHH Syndrome © 2001 Ross Products Division

B. Provide Alternate Metabolic Pathways
1. Prescribe L-citrulline (CIT) or L-ORN as indicated (7, 9, 19, 27, 30, 35).
2. Prescribe sodium phenylbutyrate to help decrease accumulated toxic precursors (1, 22, 43).
C. Supplement "Conditionally Essential" and Essential Nutrients

1. Supply L-carnitine in adequate amounts to maintain normal plasma concentration of free
carnitine (> 30 µmol/L).
2. Use Cyclinex to supply approximately 50% of prescribed protein.

1. Maintain 2- to 4-hour postprandial plasma concentrations of selected amino acids in following
ranges or within normal range for age established in laboratory used (15).
Amino Acid µmol/L
Alanine 163 - 653
ORN 10 - 800
Glutamine (GLUNH2) 335 - 755
B. Plasma Ammonia Concentration (28)
1. Maintain plasma ammonia concentration < 35 µmol/L or within normal range for age
established in laboratory used.

in adults.
b. Prevent orotic aciduria.
c. Prevent bone demineralization.
D. Behavior and Neurologic Status

1. Prevent anorexia.
2. Maintain normal neurologic status.
1. Prevent liver disease.

A. L-CIT or L-ORN
1. Prescribe L-CIT or L-ORN for patients (7, 9, 13).
2. Requirements vary:
a. From patient to patient, depending on:
1) Age.
2) Extent of transport protein defect.
3) Plasma ammonia concentration
b. In most cases, amount prescribed is between 75 and 150 mg/kg (7).
B. Protein (7-10, 39)

2. Amount prescribed may need to be increased if sodium benzoate or phenylbutyrate is
administered daily.
© 2001 Ross Products Division HHH Syndrome 413

and adults (4-9); and may result in hyperammonemia.
C. Energy
2. Requirements will vary widely and may be 5% to 10% greater than those listed in Table 23-1,
Warning: Inadequate energy intake will result in poor growth in infants and weight loss
in children and adults, decreased dietary protein tolerance, and increased
body protein catabolism causing hyperammonemia.
D. Fluid
E. Cyanocobalamin, Niacin, Folate, Pantothenic Acid, Pyridoxine
1. Sodium phenylacetate and sodium phenylbutyrate.
a. Phenylacetic acid conjugates with GLUNH2 in the liver (1) and with GLUNH2 or taurine in
kidney (22) and enhances excretion of waste nitrogen as phenylacetylglutamine.
b. Cyanocobalamin, folate, niacin, and pantothenic acid are required for conjugation
reactions (46).
c. Prescribe vitamins listed above at 3 to 5 times RDAs for age (Appendices 13 and 14,
pp A-14 and A-15) when sodium benzoate or sodium phenylbutyrate is administered

A. L-CIT or L-ORN (Appendix 26, p A-28)
1. Solutions of L-CIT and L-ORN:
a. Mix weighed amounts of L-CIT or L-ORN with boiled, cooled water to make known
volumes of each that supply 100 mg/mL (eg, 100 g of L-CIT or L-ORN with water to make
1 liter).
b. Refrigerate in sterilized, closed containers until used. Discard unused suspensions after
c. Shake well before using. Measure into Cyclinex mixture with disposable syringe.
B. Protein
(Table 23-2, p 414) required to fill approximately 50% of the protein prescription. Use infant
formula with iron until 1st birthday.
a. See Servings Lists for PHE-Restricted Diets (Protocol 1, pp 13-26) for portion sizes.
adults.
C. Energy
1. Calculate energy provided by infant formula, beikost, table foods, and Cyclinex (Table 23-2,
3. Provide remaining prescribed energy with Polycose ® Glucose Polymers powder (23
kcal/Tbsp, 3.8 kcal/g) or liquid (2 kcal/mL) (Appendix 9, p A-9); Pro-Phree ® Protein-Free
Energy Module With Iron, Vitamins and Minerals (Appendix 11, p A-10), sugar (48 kcal/Tbsp),
or Free Foods B (Table 23-2, p 414), depending on age of patient.

1. Add sufficient boiled, cooled water to infant formula, Cyclinex, and carbohydrate (if needed) to
yield prescribed volume.
can of Cyclinex and store in refrigerator. Use within 1 month after opening.
E. Cyanocobalamin, Niacin, Folate, Pantothenic Acid, Pyridoxine (Appendix 11, p A-10, for
composition of supplement)
1. Prescribe daily supplement, if required.
2. Folate requires prescription.
F. Sodium Phenylbutyrate or Sodium Benzoate (Appendix 26, p A-28)

1. Administer appropriate amount with each feed or 1/4th to 1/3rd daily dose with each meal,
depending on number of meals fed daily (3).
G. Diet Guide
each diet change.

a. See Table 23-2, p 414, for composition of infant formulas, beikost, whole cow's milk, and
Cyclinex.
a. See Table 22-4, p 402, for Cyclinex and Appendices 4 through 7, pp A-4 to A-7, for
complete nutrient composition of infant formulas.
not available.
c. If Cyclinex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
supplements).

B. Osmolarity
renal solute load.
recalculate.

1. Initial.
a. Evaluate twice weekly by quantitative methods until plasma concentrations stabilize.
2. Ongoing.
b Evaluate every 2 to 3 months when patients condition is stable.
3. Unacceptable concentrations.
a. If any plasma amino acid concentration is below lower limit of normal noted in Section V,
Establish Goals of Nutrition Support, p 407, and patient has ingested full prescription:
1) Increase prescribed amount of Cyclinex by 10% and reevaluate plasma
concentrations in 3 to 7 days.
2) If any amino acid concentration continues below its lower limit of normal, repeat
above process until value is in the treatment range.
b. If any plasma amino acid concentration is greater than upper limit of normal noted in
Section V, Establish Goals of Nutrition Support, p 407, and patient has ingested full
prescription:
1) Decrease prescribed amount of amino acid that is elevated by 10% and reevaluate in
3 days.
2) If any amino acid concentration continues above its upper limit of normal, repeat
above process until value is in the treatment range.
4. Elevated plasma glutamine concentrations may indicate impending hyperammonemia.
a. Obtain 3-day diet diary.
b. Evaluate for infection.
c. Obtain plasma ammonia concentration.
d. If no infection is present, protein intake is not greater than prescribed, and energy intake is
adequate, decrease prescribed protein by 10% and reevaluate plasma glutamine
e. Repeat above process until plasma ammonia and glutamine concentrations are in
treatment ranges.

1. Initial.
a. Evaluate daily until concentration is in normal range, < 35 µmol/L.
2. Ongoing.
a. Evaluate weekly until patient is 6 months old, twice monthly until 1 year of age, and
monthly thereafter if patient is well.

3. Elevated plasma ammonia concentration.
a. Obtain 3-day diet diary and evaluate patient for infection. If no infection is found, protein
intake is not greater than prescribed, and energy intake is not less than prescribed:
1) Increase L-CIT or L-ORN by 10% or increase sodium phenylbutyrate by 10% (if not
already at upper limit tolerated) and reevaluate plasma ammonia concentration in 1 to
2 days.
2) If plasma ammonia concentration remains above upper limit of normal, repeat
process until value is in normal range.
Warning: Over-restriction of protein and/or energy will result in increase in plasma
ammonia concentration.
C. Protein Status (41)

c. Evaluate plasma ammonia and plasma glutamine concentrations within 3 to 7 days after
each increase in prescribed protein.
3. If protein catabolism is suspected, verify by measuring 3-methylhistidine in urine.
a. Urinary 3-methylhistidine excretion > 25 µmol/mol creatinine suggests catabolism (21).
D. Iron Status
E. Plasma Sodium and Potassium Concentrations
1. Plasma sodium concentration.
a. If sodium phenylbutyrate or sodium benzoate is prescribed, evaluate within 2 to 3 days
after each prescription change.
2. Plasma potassium concentration
a. If Polycitra ® K Oral Solution is used, evaluate on a routine basis.
F. Growth Status
a. Measure monthly to 1 year, every 3 months until prepubertal growth spurt is completed,
achieved.

c. Evaluate plasma ammonia and GLUNH2 concentrations with each increase in prescribed
protein.
G. Nutrient Intake
and 25, pp A-26 and A-27).
not available.
H. Clinical Summary
A. Example 1
Establish and fill prescription for male neonate weighing 3.0 kg using Recommended Daily
Nutrient Intakes from Table 23-1, p 414, and approximate nutrient contents from Table 23-2, p
414.
L-CIT 150 mg X 3.0 kg = 450 mg/day
Vitamin B supplements, if indicated
(mg) (g) (kcal)
Cyclinex-1 44 g 0 3.3 224
Similac With Iron, Ready to Feed 236 Ml 0 3.3 160
L-CIT 1 4.5 mL 450 0.0 0
Total per day 450 6.6 450

Total per kg 150 2.2 150
is < 110 mosm.
1
B. Example 2
Establish and fill prescription for 24-month-old child weighing 13.0 kg using Recommended Daily
Nutrient Intakes from Table 23-1, p 414, and approximate nutrient contents from Table 23-2,
p 414.
L-ORN 1,950 mg /day
Protein 20 g
Energy 1,365 kcal
Fluid 1,495 mL

Medical Food Mixture Measure ORN Protein Energy
(mg) (g) (kcal)
Cyclinex-1 180 g 0 13.5 927
L-ORN 19.5 mL 1,950 0.0 0
Food List Servings

Fats 1 0 0.1 60
Fruits 4 0 2.0 240
Total per day 1,950 20.0 1,387
C. Example 3
Establish and fill prescription for 7-year-old child weighing 25.0 kg using Recommended Daily
Nutrient Intakes from Table 23-1, p 414, and approximate nutrient contents from Table 23-2,
p 414.
L-ORN 3,750 mg /day
Protein 25 g
Energy 1,730 kcal
Fluid 2,125 mL
Vitamin B supplements
Medical Food Mixture Measure ORN Protein Energy
(mg) (g) (kcal)
Cyclinex-2 100 g 0 15.0 410
L-CIT 1 37.5 mL 3,750 0.0 0
Sugar 1/4 cup 0 0.0 192
Food List Servings

Fats 8 0 0.8 480
Fruits 7 0 3.5 420
Total per day 3,750 24.9 1,722
Approximate osmolarity of medical food mixture is < 600 mosm/L

A. Rationale
protein (44).
2. Well-nourished patients with HHH syndrome respond to infection and trauma as do normal
persons.
Warning: Prolonged use (> 2 days) of protein-free or low-energy diet will lead to body
protein catabolism and rebound hyperammonemia.

TABLE 23-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With HHH
Syndrome
Age Nutrient
1-3
Protein Energy 2, Fluid 4
Infants
0 to < 3 mo 2.20 - 1.25 150 - 125 160 - 130
3 to < 6 mo 2.00 - 1.80 140 - 120 160 - 130
6 to < 9 mo 1.80 - 1.60 130 - 115 150 - 125
9 to < 12 mo 1.60 - 1.40 120 - 110 130 - 120

Girls and Boys
1 to < 4 yr 16 - 20 945 - 1,890 945 - 1,890
4 to < 7 yr 20 - 25 1,365 - 2,415 1,365 - 2,415
7 to < 11 yr 25 - 30 1,730 - 3,465 1,730 - 3,465
Women
11 to < 15 yr 42 - 46 1,575 - 3,150 1,575 - 3,150
15 to < 19 yr 40 - 44 1,260 - 3,150 1,260 - 3,150
≥ 19 yr 42 - 46 1,785 - 2,625 1,785 - 2,625
Men
11 to < 15 yr 50 - 55 2,100 - 3,885 2,100 - 3,885
15 to < 19 yr 55 - 60 2,200 - 4,095 2,200 - 4,095
≥ 19 yr 60 - 65 2,625 - 3,465 2,625 - 3,465
1
From references 8 and 10.
2
From reference 10.
3
Protein intake may need to be increased if sodium benzoate or sodium phenylbutyrate is prescribed.
4
TABLE 23-2. Serving Lists for Protein-Restricted Diets: Approximate Nutrient Content per Serving
Food List Nutrient

Protein Energy
(g) (kcal)
Breads/Cereals 0.6 30
Fats 0.1 60
Fruits 0.5 60
Vegetables 0.5 10
Free Foods A 0.1 65
Free Foods B 0.0 55
1
Cyclinex-1 ®, 100 g 7.50 510
Cyclinex-2 ®, 100 g 15.00 440
1
1
Similac ® With Iron Infant Formula, Ready to Feed, 100 mL 1.40 68
2
1
2

TABLE 23.3 HHH Syndrome Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

Length/ Weight Head ALA GLUNH2 ORN Creatine Ammonia Hgb Hct Ferritin Transthyretin L-CIT / Protein Energy
Height Circum ORN
(mo/d/yr) (yrs/mo) (cm) (kg) (cm) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (g/dL) (%) (ng/mL) (mg/dL) (mg) (g) (kcal)
HHH Syndrome 415
REFERENCES
1. Ambrose AM, Powder FW, Sherwin CP: Further studies on the detoxification of phenylacetic acid. J Biol Chem
1933;101:669-675.
Dis 2000;23 (Suppl 1):29A.
3. Bachman C: Diagnosis of urea cycle disorders. In Tada K, et al (eds): Recent Advances in Inborn Errors of
Metabolism. New York: S Karger, 1987, pp 233-241.
4. Bachman C: Urea cycle disorders. In Fernandes J, et al (eds): Inborn Metabolic Diseases: Diagnosis and
1996.
6. Chadefaux B, Bonnefont JP, Rabier D, et al: Potential for the prenatal diagnosis of hyperornithinemia,
hyperammonemia and homocitrullinuria syndrome. Am J Med Genet 1989;32:264 (letter).
7. Dionisi Vici C, Bachmann C, Gambarara M, et al: Hyperornithinemia-hyperammonemia-homocitrullinuria
syndrome: Low creatine excretion and effect of citrulline, arginine or ornithine supplement. Pediatr Res
1987;22:364-367.
1985.
9. Fell V, Pollitt RJ, Sampson GA, Wright T: Ornithinemia, hyperammonemia, and homocitrullinuria. Am J Dis Child
1974;127:752-746.
11. Gatfield PD, Taller, E, Wolfe, DM, Haust D: Hyperornithinemia, hyperammonemia, and homocitrullinuria
associated with decreased carbamylphosphate synthetase I activity. Pediatr Res 1975;9:488-497.
12. Gjessing LR, Lunde HA, Undrum T, et al: A new patient with hyperornithinemia, hyperammonemia and
homocitrullinuria syndrome treated early with low protein diet. J Inher Metab Dis 1986;9:186-192.
13. Gordon BA, Gatfield DA, Haust AD: The hyperornithinemia, hyperammonemia, homocitrullinuria syndrome: An
ornithine transport defect remediable with ornithine supplements. Clin Invest Med 1987;10:329-336.
14. Gray RGF, Green A, Hall S, McKeown C: Prenatal exclusion of HHH syndrome. Prenatal Diagn 1995;15:474-476.
15. Gregory DM, Sovetts D, Clow CR: Plasma free amino acid values in normal children and adolescents. Metabolism
1986;35:967-969.
17. Hommes FA, Ho CR, Roesel RA, et al: Decreased transport of ornithine across the inner mitochondrial membrane
as a cause by hyperornithinaemia. J Inher Metab Dis 1982;5:41-47.
18. Hommes FA, Roesel RA, Metoki K, et al: Studies on a case of HHH-syndrome (hyperornithinemia,
hyperammonemia,homocitrullinuria). Neuropediatr 1986;17:48-52.
19. Inoue I, Koura M, Saheki T, et al: Abnormality of citrulline synthesis in liver mitochondria from patients with
hyperornithinaemia, hyperammonaemia and homocitrullinuria. J Inher Metab Dis 1987;10:227-280.
20. Inoue I, Saheki T, Kayanuma K, et al: Biochemical analysis of decreased ornithine transport activity in the liver
mitochondria from patients with hyperornithinemia, hyperammonemia and homocitrullinuria . Biochem Biophys
Acta 1988;964:90-95.
21. Jackson AA, Badaloo AV, Forrester T, et al: Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index
of glycine insufficiency in normal man. Brit J Nutr 1987;58:207-214.
22. James MO, Smith RL, Williams RT, Reidenberg M: The conjugation of phenylacetic acid in man, sub-human
primates and some non-primate species. Proc R Soc Lond 1972;182:25-35.
23. Koike R, Fujimori K, Yuasa T, et al: Hyperornithinemia, hyperammonemia and homocitrullinuria: Case report and
biochemical study. Neurol 1987;37:1813-1815.
1982.
1987;1:1-17.
26. Meites S (ed): Pediatric Clinical Chemistry: Reference Normal Values, ed 3. Washington, DC: American
Association for Clinical Chemistry, 1989.
27. Nakajima M, Ishii S, Mito T, et al: Clinical, biochemical and ultrastructural study on the pathogenesis of
hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. Brain Dev 1988;10:181-185.
28. Oyanagi K, Tsichiyama A, Itakura Y, et al: The mechanism of hyperammonaemia and hyperornithinaemia in the
syndrome of hyperornithinaemia, hyperammonaemia and homocitrullinuria. J Inher Metab Dis 1983;6:133-134.

30. Rodes M, Ribes a, Pineda M, et al: A new family affected by the syndrome of hyperornithinaemia,
hyperammonaemia and homocitrullinuria. J Inher Metab Dis 1987;10:73-81.
31. Schoeffer A, Herrmann E, Broesicke HG, Moench E: Effect of dosage and timing of amino acid mixtures on
32. Shih VE, Mandell R, Herzfeld A: Defective ornithine metabolism in cultured skin fibroblasts from patients with the
syndrome of hyperornithinemia, hyperammonemia, and homocitrullinuria. Clin Chim Acta 1982;118:149-157.
33. Shih VE, Efron ML, Moser HW: Hyperornithinemia, hyperammonemia and homocitrullinuria: A new disorder or
amino acid metabolism associated with myoclonic seizures and mental retardation. Am J Dis Child
1969;117:83-92.
34. Shimizu H, Maekawa K, Eto Y: Abnormal urinary excretion of polyamines in HHH syndrome. Brain Dev
1990;12:533-535.
35. Simell O, MacKenzie S, Clow CL, Scriver CR: Ornithine loading did not prevent induced hyperammonemia in a
patient with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome. Pediatr Res 1985;19:1283-1287.
1976.
1983;7:280-288.
38. Smith L, Lambert P, Brochu P, et al: Hyperornithinemia, hyperammonemia, homocitrullinuria (HHH) syndrome:
Presentation as acute liver disease with-CoAgulopathy. J Pediatr Gastroenterol Nutr 1992;15:431-436.
39. Snyderman SE, Holt LE, Dancis J, et al: "Unessential" nitrogen: A limiting factor for human growth. J Nutr
1962;78:57-52.
1989;143:828-832.
41. Torun B, Chew F: Protein-energy malnutrition. In Shils ME, et al (eds): Modern Nutrition in Health and Disease,
42. Tsujino S, Suzuki T, Azuma T, et al: Hhyperornithinemia, hyperammonemia, and homocitrullinuria — A case
report and study of ornithine metabolism using in vivo deuterium labeling. Clin Chim Acta 1991;201:129-134.
43. Tuchman M, Knopman DS, Shih VE: Episodic hyperammonemia in adult siblings with hyperornithinemia,
hyperammonemia, and homocitrullinuria syndrome. Arch Neurol 1990;47;1134-1137.
1977;30:1269-1280.
45. Zammarchi E, Ciani F, Pasquini E, et al: Neonatal onset of hyperornithinemia-hyperammonemia-homocitrullinuria
syndrome with favorable outcome. J Pediatr 1997;131:440-443.
46. Zeman FJ: Clinical Nutrition and Dietetics, ed 2. New York: MacMillan Publishing Co, 1991.

PROTOCOL 24 — Urea Cycle Disorders

I. Introduction
Disorders of the urea cycle result from inherited defects in any one of six enzymes which function in
urea production (Figure T). With the exception of ornithine transcarbamylase (OTC) deficiency, all
have an autosomal recessive mode of inheritance. OTC deficiency is inherited as an X-linked
dominant trait that is often lethal in males (3,4, 8, 9).
Ammonia is normally converted to urea in the liver through the Krebs-Henseleit cycle (Figure T) and
excreted in urine. The first three enzymes of the cycle and N-acetylglutamate synthetase (NAGS) are
mitochondrial. NAGS catalyzes conversion of acetyl-CoA plus glutamate to N-acetylglutamine, an
essential cofactor for carbamylphosphate synthesis. Carbamylphosphate synthetase (CPS) catalyzes
conversion of ammonia, ATP, and bicarbonate to carbamylphosphate. OTC utilizes
carbamylphosphate and ornithine (ORN) as cosubstrates to form citrulline (CIT). CIT is exported from
mitochondria to the cytoplasm where cytosolic reactions are linked to those three mitochondria
functions. CIT and aspartate form argininosuccinic acid, in a reaction catalyzed by argininosuccinic
acid synthetase (AS). Fumarate is cleaved from argininosuccinic acid by argininosuccinic acid lyase
(AL), yielding arginine (ARG). Urea is then formed by the action of arginase, regenerating cytosolic
ORN which is transported back into the mitochondria to react with OTC (3, 4, 8, 9).
Restrict Prevent (N) Therapeutic phenylacetate

Serine tissue protein Glutamine
dietary (N)
protein catabolism
Folate
(N)
Phenylacetylglutamine Urine
(N)
+
Glycine (N) (NH4) + CO2
Therapeutic
N-acetylglutamate Acetyl-CoA + Glutamate
benzoate
Carbamylphosphate
N-acetylglutamate Oxaloacetate
synthetase
synthetase
Hippurate (N)
Orotic
Carbamylphosphate acid
L-citrulline L-aspartate
Urine
Ornithine Argininosuccinate
= Site of enzyme defect transcarbamylase synthetase
(N) = nitrogen
L-ornithine L-argininosuccinate
Argininosuccinate
Urea Arginase lyase
L-arginine
Urine
Therapeutic L-arginine
Fumarate
Figure T. Nitrogen metabolism in urea cycle enzyme defects.
Hyperammonemia is a biochemical manifestation of all disorders of the urea cycle. Other biochemical
characteristics of each defect follow: CPS deficiency causes decreased plasma CIT concentration;
OTC deficiency results in orotic aciduria and X-linked patterns of transmission; AS deficiency is
424 Urea Cycle Disorders © 2001 Ross Products Division
associated with increased plasma CIT concentration accompanied by orotic aciduria; AL deficiency
causes increased argininosuccinate in plasma and urine; and arginase deficiency results in increased
ARG concentration in plasma and urine. Clinical features in the newborn suggestive of urea cycle
enzyme defects occur with protein ingestion or infection with body protein catabolism. In increasing
order of severity, these defects include poor feeding, vomiting, lethargy, hypotonia, stupor, bleeding
diatheses, convulsions, coma, shock, and death (19). Mental retardation occurs in survivors of these
newborn episodes (3,4, 8, 9, 52). Orthoptic liver transplantation has been successfully used for
patients with CPS and OTC deficiencies (9). Retroviral-mediated gene therapy is being studied in AS-
deficient cell cultures (12). Tamura, et al (50) found that glucagon enhanced urea excretion in AS
deficiency.

Results of therapy in infants with complete or near complete enzyme deficiencies have been less than
optimal with delayed death and below normal development. If serious brain swelling and coma are
prevented in the neonatal period or if onset of disease expression is delayed, physical growth and
mental development are more nearly normal with nutrition and pharmacologic support. If diagnosis is
anticipated and treatment is begun during the early neonatal period in affected siblings with
citrullinemia or argininosuccinic aciduria (ASA), relatively normal outcome is observed, even in the
severe enzyme defects (33, 34, 37, 41, 43). Females heterozygous for OTC deficiency may expire
during the neonatal period (19), may develop coma during the postpartum period (15, 55) or if
parenteral nutrition is administered (15), or may be developmentally delayed if untreated (17, 33, 42).
A female with arginase deficiency was reported to develop coma on the first day of her menstrual
period and spontaneously recover 3 days later (22).

A. The Defect
1. Hyperammonemia may result from a defect in any of the following enzymes:
a. NAGS (10, 23).
b. CPS.
c. OTC.
d. AS.
e. AL.
f. Arginase - plasma ammonia may be normal in some instances.
a. Poor feeding, vomiting, lethargy, hypotonia, spasticity, irritability, twitching, seizures,
apnea or coma.
b. Plasma ammonia concentration > 150 µmol/L in newborn period and > 80 µmol/L
thereafter (3).
2. See references 3, 4, and 8-10 for methods of diagnosis.
3. Other causes of inherited hyperammonemia must be ruled out, including the following:
a. Abnormalities of fatty acid metabolism (Protocol 20).
b. Transport defects of urea cycle intermediates - lysinuric protein intolerance (Protocol 11),
and hyperornithinemia-hyperammonemia-homocitrullinemia syndrome (Protocol 23).
c. Organic acidurias (Protocols 5, 6, 10, 13, 18, 20).
4. Causes of acquired hyperammonemia that must be ruled out include the following:
a. Deficient ARG supply.
b. Reye's syndrome.
c. Transient hyperammonemia of newborn.
d. Valproate therapy (31, 38, 45).
Warning: Laboratory results MUST be available within 4 to 8 hours when a disorder of
urea cycle enzyme is suspected as hyperammonemia is a metabolic
emergency.

1. Restrict dietary protein to amount tolerated without causing hyperammonemia (5).
© 2001 Ross Products Division Urea Cycle Disorders 425

2. Prevent excessive body protein catabolism (5).
3. Restrict dietary tryptophan to that required for growth to prevent excess synthesis of serotonin
(25) and quinolinic acid (6).
B. Provide Alternate Metabolic Pathways (28)
1. Prescribe L-ARG or L-CIT as indicated.
2. Prescribe sodium benzoate, sodium phenylacetate or sodium phenylbutyrate to help decrease
accumulated toxic precursors.
C. Supplement "Conditionally Essential" and Essential Nutrients
1. Supply L-ARG (20) (except in arginase deficiency), L-carnitine (39), L-cystine, and L-tyrosine
in adequate amounts (30).
2. Administer N-carbamylglutamate to patients with deficiency of NAGS or CPS (29).
3. Use essential amino acid mix to supply approximately 50% of prescribed protein.

1. Maintain 2- to 4-hour postprandial plasma concentrations of selected amino acids in following
ranges or within normal range for age established in laboratory used.
Amino Acid µmol/L mg/dL Reference
ARG 100 -150 1.75 -2.60 1
Aspartic acid (ASP) 14 - 50 0.18 - 0.67 36
CIT 30 - 128 0.52 - 2.24 36
Glutamine 335 - 755 4.90 - 11.04 36
Glycine (GLY) 100 - 170 0.75 - 1.28 36
Serine (SER) 100 - 170 1.05 - 1.79 36
B. Plasma Ammonia Concentration (3-5, 53)
1. Maintain plasma ammonia concentration < 35 µmol/L or within normal range for age
established in laboratory used.
in adults.
a. Prevent ARG deficiency (20).
b. Prevent hyperlipidemia.
c. Prevent catabolism.
d. Prevent orotic aciduria in deficiencies of AL, AS, and OTC (3-6).
D. Behavior and Neurologic Status
1. Prevent anorexia (25).
2. Maintain normal neurologic status.
1. Prevent liver disease (30).

A. L-ARG
1. Prescribe L-ARG for patients who have deficiency of either AL or AS. Do not prescribe for
patients with arginase deficiency.
a. Becomes essential amino acid in most disorders of the urea cycle (13)
b. Enhances waste nitrogen excretion.

2. Requirements vary:
a. From patient to patient, depending on age, extent of enzyme defect, and plasma ARG
concentration
b. In most cases, amount prescribed is between 400 and 700 mg/kg (8, 9).
B. L-CIT
1. May be used instead of L-ARG in CPS or OTC deficiencies
2. Initially, prescribe 170 mg/kg (8, 9),
3. Amount to prescribe depends on:
a. Age.
b. Extent of enzyme defect.
c. Plasma CIT concentration
C. Citrate
1. Patients with treated AS and AL deficiencies have been found to have very low citrate
excretion (3).
2. Some clinicians prescribe 2.2 to 3.0 mmol/kg per 24 hours (3, 26).
3. Greater amounts may be required during periods of illness accompanied by fever.
D. Protein (13, 48)
2. Amount prescribed may need to be increased if sodium benzoate, sodium phenylacetate, or
sodium phenylbutyrate is administered daily.
and adults; and may result in hyperammonemia (51).
E. N-Carbamylglutamate (10, 23)
1. Patients with deficiency of NAGS or CPS may not require protein restriction if
N-carbamylglutamate is administered.
2. Administer 80 to 100 mg/kg daily.
3. L-ARG supplements and drugs used to enhance waste nitrogen may be unnecessary when
N-carbamylglutamate is administered.
F. Energy
catabolism (3, 4) (Table 24-1, p 429).
2. Requirements will vary widely and may be 5%-10% greater than those listed in Table 24-1,
Warning: Inadequate energy intake will result in low plasma transthyretin
concentration, poor growth in infants and weight loss in children and adults,
decreased dietary protein tolerance, and increased body protein catabolism
causing hyperammonemia.
G. Fluid
H. Cyanocobalamin, Niacin, Folate, Pantothenic Acid, Pyridoxine

1. Sodium benzoate.
a. Enhances waste nitrogen excretion through conjugation of GLY with benzoic acid to form
hippuric acid (18).
b. GLY biosynthesis and conjugation of GLY with benzoate require adequate cellular
concentrations of cyanocobalamin, niacin, folate, pantothenic acid, and pyridoxine (56).
c. Prescribe vitamins listed above at 3 to 5 times Recommended Dietary Intakes (RDIs) for
age (Appendices 13 and 14, pp A-14 and A-15) when sodium benzoate is administered.

2. Sodium phenylacetate and sodium phenylbutyrate.
a. Phenylacetic acid conjugates with glutamine in the liver (1) and with glutamine or taurine
in kidney (28) and enhances excretion of waste nitrogen as phenylacetylglutamine.
b. Cyanocobalamin, niacin, folate, and pantothenic acid are required for conjugation
reactions (56).
c. Prescribe vitamins listed above at 3 to 5 times RDIs for age (Appendices 13 and 14,
pp A-14 and A-15) when phenylacetate or phenylbutyrate is administered.
VII. Fill Prescription (4)

A. L-ARG or L-CIT (Appendix 26, p A-28)
1. Solutions of L-ARG and L-CIT
a. Mix weighed amounts of L-ARG and L-CIT with boiled, cooled water to make know
volumes of each to yield 100 mg/mL (eg, 100 g of L-ARG or L-CIT with enough water to
make 1 liter).
b. Measure into Cyclinex mixture with disposable syringe.
c. Refrigerate in sterilized, closed containers until used. Discard unused suspensions after
d. Shake well before using.
Warning: Use only ARG-free base.
B. Citrate
1. When citrate is prescribed, Polycitra ® K Oral Solution may be used.
2. May be ordered from:
Baker Norton Pharmaceuticals, Inc.
8800 NW 36th St
Miami, FL 33178-2404
Phone: 800 735-2315.
C. N-Carbamylglutamate
1. Administer 1/4th to 1/8th of prescribed dose before each feed, depending on number of feeds.
2. May be ordered from:
Curtin & Warner
19 Phoenix Place
Lewis, East Sussex, UK
D. Protein
1. Calculate amount of infant formula with iron (use until 1st birthday), beikost, whole cow's milk,
or table foods (Table 24-2, p 429) required to fill approximately 50% of the protein
prescription.
a. See Servings Lists for PHE-Restricted Diets (Protocol 1, pp 13-26) for portion sizes.
adults.
E. Energy
1. Calculate energy provided by infant formula, beikost, whole cow's milk, or table foods and
Cyclinex (Table 24-2, p 429) required to fill protein prescription.
Energy Module With Iron, Vitamins and Minerals (Appendix 11, p A-10), sugar (48 kcal/Tbsp),
or Free Foods B (Table 24-2, p 429), depending on age of patient.

1. Add sufficient boiled, cooled water to infant formula, Cyclinex, and carbohydrate (if needed) to
yield prescribed volume. Tap water may replace boiled, cooled water when preparing Cyclinex
for older infants, children, and adults.
G. Cyanocobalamin, Niacin, Folate, Pantothenic Acid, Pyridoxine (Appendix 26, p A-28)
1. Prescribe daily supplement, if needed.
2. See Appendix 11, p A-10, for composition of supplement.
3. Folate requires prescription.
H. Sodium Benzoate, Sodium Phenylacetate, Sodium Phenylbutyrate (Appendix 26, p A-28)
1. Administer appropriate amount with each feed or 1/6th to 1/8th daily dose with each meal,
depending on number of meals fed daily.
I. Diet Guide
each diet change.

a. See Table 24-2, p 429, for composition of Cyclinex, infant formulas, beikost, and whole
cow's milk.
2. Check diet to determine if it supplies RDIs of minerals and vitamins (Appendices 13 and 14,
pp A-14 and A-15).
a. See Table 22-4, p 402, for composition of Cyclinex and Appendices 4 through 7, pp A-4 to
not available.
c. If Cyclinex mixture provides < 100% of RDIs for infants and < 75% for children and adults,
supplement diet with needed minerals and vitamins if laboratory tests indicate need
(Appendix 11, p A-10, for composition of supplements).
B. Osmolarity

renal solute load.
recalculate.

1. Initial.
a. Evaluate twice weekly by quantitative methods until plasma concentrations normalize to
prevent deficiency.
2. Ongoing.
b Evaluate every 2 to 3 months when patients condition is stable.
3. Unacceptable plasma amino acid concentrations.
a. If any plasma amino acid concentration is below lower limit of normal noted in Section V,
Establish Goals of Nutrition Support, p 420, and patient has ingested full protein
prescription:
1) Increase prescribed Cyclinex by 10% and reevaluate plasma concentrations in 3 to
7 days.
2) If any amino acid continues below its lower limit of normal, repeat above process until
b. If any plasma GLUNH2 concentration is greater than upper limit of normal noted
Section V, Establish Goals of Nutrition Support, p 420, and patient has ingested full
prescription:
1) Decrease prescribed amount of protein from natural foods by 10% and reevaluate in
3 days.
2) If GLUNH2 concentration continues above its upper limit of normal, repeat above
4. Elevated plasma GLUNH2 concentrations may indicate impending hyperammonemia.
a. Obtain 3-day diet diary.
b. Evaluate for infection.
c. Obtain plasma ammonia concentration.
d. If no infection is present, protein intake is not greater than prescribed, and energy intake is
adequate, decrease prescribed protein by 10% and reevaluate plasma glutamine
e. Repeat above process until ammonia and GLUNH2 concentrations are in treatment ranges.
1. Initial.
a. Evaluate daily until concentration is in normal range.
2. Ongoing.
a. Evaluate weekly until patient is 6 months old, twice monthly until 1 year of age, and
monthly thereafter if patient is well.
3. Elevated plasma ammonia concentration (36).
a. Obtain 3-day diet diary and evaluate patient for infection. If no infection is found, protein
intake is not greater than prescribed, and energy intake is not less than prescribed:

1) Decrease protein from natural foods by 10% or increase prescribed sodium benzoate,
sodium phenylacetate, or sodium phenylbutyrate by 10% (if not already at upper limit
tolerated) and reevaluate plasma ammonia concentration in 1 to 2 days.
2) If plasma ammonia concentration remains above upper limit of normal, repeat
process until normal concentration is achieved.
Warning: Over-restriction of protein and/or energy will result in increase in plasma
ammonia concentration.
C. Protein Status
1. Evaluate plasma transthyretin concentration monthly until patient is 1 year of age and every
a. Increase prescribed protein by 10% and reevaluate plasma transthyretin concentration in
1 month.
c. Evaluate plasma ammonia and plasma GLUNH2 concentrations with each increase in
prescribed protein.
3. If GLY deficiency is suspected, verify by measuring pyroglutamic acid in urine (27).
a. Urinary pyroglutamic acid excretion > 325 µmol/mmol creatinine suggests GLY deficiency.
4. If protein catabolism is suspected, verify by measuring 3-methylhistidine in urine.
a. Urinary 3-methylhistidine excretion > 25 µmol/mol creatinine suggests catabolism.
D. Iron Status
b. Normal heme synthesis requires adequate GLY.
E. Plasma Sodium and Potassium Concentrations
1. Plasma sodium concentration.
a. If sodium benzoate, sodium phenylacetate, or sodium phenylbutyrate is prescribed,
evaluate after each prescription change.
2. Plasma potassium concentration
a. If Polycitra ® K Oral Solution is used, evaluate on a routine basis.
F. Growth Status
a. Measure monthly to 1 year, every 3 months until prepubertal growth spurt is completed,
achieved.
c. Evaluate plasma ammonia and GLUNH2 concentrations with each increase in prescribed
protein.
G. Nutrient Intake
and 25, pp A-26 and A-27).
not available.
H. Clinical Summary
A. Example 1
Establish and fill prescription for male neonate weighing 3.0 kg who has OTC deficiency using
Recommended Daily Nutrient Intakes from Table 24-1, p 429, and approximate nutrient contents
from Table 24-2, p 429.
L-CIT 350 mg X 3.0 kg = 1,050 mg/day
Citrate
(mg) (g) (kcal)
Cyclinex-1 44 g 0 3.3 224
Similac With Iron Ready to Feed 236 mL 0 3.3 160
L-CIT 1 10.5 mL 1,050 0.0 0
Total per day 1,050 6.6 450

Total per kg 150 2.2 150
load is < 110 mosm.
1
B. Example 2
Establish and fill prescription for 24-month-old child weighing 13.0 kg who AS deficiency using

L-ARG 7,150 mg /day
Protein 13 g
Energy 1,365 kcal
Fluid 1,495 mL
Citrate
(mg) (g) (kcal)
Cyclinex-1 87 g 0 6.5 444
1
L-ARG 72 mL 7,200 0.0 0
Polycose powder 34 g 0 0.0 129
Food List Servings

Breads/Cereals 3 --- 1.8 90
Fats 3 --- 0.3 180
Fruits 4 --- 2.0 240
Vegetables 4 2.0 40
Total per day 7,200 13.0 1,363
is < 110 mosm.
1
C. Example 3
Establish and fill prescription for 7-year-old girl weighing 25.0 kg who has CPS deficiency using
L-CIT 8,750 mg /day
Protein 17 g
Energy 1,730 kcal
Fluid 2,125 mL
Citrate

Medical Food Mixture Measure CIT Protein Energy
(mg) (g) (kcal)
Cyclinex-2 57 g 0 8.6 51
1
L-CIT 87.5 mL 8750 0.0 0
Sugar 60 g 0 0.0 240
Food List Servings

Fats 8 0 0.8 480
Fruits 7 0 3.5 420
Total per day 8,750 17.7 1,766
XI GLY, GLUNH2, Protein, and Nitrogen Deficiencies

A. GLY Deficiency
1. Decreased heme synthesis (27).
2. Decreased glutathione synthesis (27).
B. GLUNH2
1. Decreased purine and pyrimidine biosynthesis.
C. Protein
1. Kwashiorkor (51).
D. Nitrogen
1. No weight gain, decreased weight gain, or weight loss (48).
2. Impaired nitrogen retention (48).
3. Protein malnutrition (48).

A. Rationale
1. In normal persons, febrile illness and trauma are accompanied by catabolism of body protein
(54).
2. See references 3, 8, 9, and 13 for management.
Warning: Prolonged use (> 2 days) of protein-free or low-energy diet will lead to protein
catabolism and rebound hyperammonemia.
B. Contraindicated Medication
1. Valproate (31, 38, 45).

TABLE 24-1. Recommended Daily Nutrient Intakes (Ranges) for Infants, Children, and Adults With Urea
Cycle Disorders
Age Nutrient
1-3
Protein Energy 1 Fluid 4
Infants
0 to < 3 mo 2.20 - 1.25 150 - 125 160 - 130
3 to < 6 mo 2.00 - 1.80 140 - 120 160 - 130
6 to < 9 mo 1.80 - 1.60 130 - 115 150 - 125
9 to < 12 mo 1.60 - 1.40 120 - 110 130 - 120

Girls and Boys
1 to < 4 yr 8 - 12 945 - 1,890 945 - 1,890
4 to < 7 yr 12 - 15 1,365 - 2,415 1,365 - 2,415
7 to < 11 yr 14 - 17 1,730 - 3,465 1,730 - 3,465
Women
11 to < 15 yr 20 - 23 1,575 - 3,150 1,575 - 3,150
15 to < 19 yr 20 - 23 1,260 - 3,150 1,260 - 3,150
≥ 19 yr 22 - 25 1,785 - 2,625 1,785 - 2,625
Men
11 to < 15 yr 20 - 23 2,100 - 3,885 2,100 - 3,885
15 to < 19 yr 21 - 24 2,200 - 4,095 2,200 - 4,095
≥ 19 yr 23 - 32 2,625 - 3,465 2,625 - 3,465
1
From references 14, 16.
2
From reference 13, 16.
3
Protein intake may need to be increased if sodium benzoate, sodium phenylacetate, or sodium phenylbutyrate is
prescribed.
5
TABLE 24-2. Serving Lists for Protein-Restricted Diets: Approximate Nutrient Content per Serving
Food List Nutrient

Protein Energy
(g) (kcal)
Breads/Cereals 0.6 30
Fats 0.1 60
Fruits 0.5 60
Vegetables 0.5 10
Free Foods A 0.1 65
Free Foods B 0.0 55
1
Cyclinex-1 ®, 100 g 7.50 510
Cyclinex-2 ®, 100 g 15.00 440
1
1
Similac ® With Iron Infant Formula, Ready to Feed, 100 mL 1.40 68
2
1
2

430 Urea Cycle Disorders
TABLE 24.3. Urea Cycle Disorders Clinical Summary Sheet
Date of Birth: __________/__________/__________

Mo Day Year

1
Length/ Weight Head ARG ASP CIT GLUNH2 GLY SER Ammonia Hgb Hct Ferritin Trans- TAG ARG CIT Protein Energy
Height Circum thyretin
(mo/d/yr) (yrs/mo) (cm) (kg) (cm) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (µmol/L) (g/dL) (%) (ng/mL) (mg/dL) (mg/dL) (mg) (mg) (g) (kcal)
1
Triacylglycerols
REFERENCES
1. Ambrose AM, Powder FW, Sherwin CP: Further studies on the detoxification of phenylacetic acid. J Biol Chem
1933;101:669-675.
Dis 2000;23 Suppl 1:29A.
3. Bachman C: Urea cycle disorders. In Fernandes J, et al (eds): Inborn Metabolic Diseases: Diagnosis and
4. Batshaw ML: Inborn errors of urea synthesis. Ann Neurol 1994;35:133-141.
5. Batshaw ML, Monahan PS: Treatment of urea cycle disorders. In Tada K, et al (eds): Recent Advances in Inborn
Errors of Metabolism. New York: Karger, 1987, pp 242-250.
6. Batshaw ML, Robinsin MB, Hyland K, et al: Quinolinic acid in children with congenital hyperammonemia. Ann
Neurol 1993;34:676-681.
1996.
8. Brusilow SW, Horwich AL: Urea cycle enzymes. In Scriver CR, et al (eds): The Metabolic and Molecular Bases of
9. Brusilow SW, Maestri NE: Urea cycle disorders: Diagnosis, pathophysiology and therapy. Adv Pediatr
1996;43:127-170.
10. Colombo JP: N-acetylglutamate deficiency: Clinical and biochemical features. Int'l Pediatr 1995;10:109-113.
11. Connelly A, Cross JH, Gadian DG, et al: Magnetic resonance spectroscopy shows increased brain glutamine in
ornithine carbamoyl transferase deficiency. Pediatr Res 1993;33:77-81.
12. Demarquoy J: Retroviral-mediated gene therapy for the treatment of citrullinemia: Transfer and expression of
argininosuccinate synthetase in human hemopoietic cells. Experientia 1993;49:345-348.
1985.
15. Felig DM, Brusilow SW, Boyer JL: Hyperammonemic coma due to parenteral nutrition in a woman with
heterozygous ornithine transcarbamylase deficiency. Gastroent 1995;109:282-284.
17. Fries MH, Kuller TA, Jurecki E, Packman S: Prenatal counseling in heterozygotes for ornithine transcarbamylase
deficiency. Clin Pediatr 1994;Sept:525-529.
18. Gatley SJ, Sherratt HAS: The synthesis of hippurate from benzoate and glycine by rat liver mitochondria.
Biochem J 1977;166:39-47.
19. Girgis N, McGravey V, Shah BL, et al: Lethal ornithine transcarbamylase deficiency in a female neonate. J Inher
Metab Dis 1987;10;274-275.
20. Goldblum OM, Brusilow SW, Maldonado YA, Farmer ER: Neonatal citrullinemia associated with cutaneous
manifestations and arginine deficiency. J Am Acad Dermatol 1986;14:321-326.
21. Gregory DM, Sovetts D, Clow CR: Plasma free amino acid values in normal children and adolescents. Metabolism
1986;35:967-969.
22. Grody WW, Chang RJ, Panagiotis NM, et al: Menstrual cycle and gonadal steroid effects on symptomatic
hyperammonaemia of urea-cycle-based and idiopathic aetiologies. J Inher Metab Dis 19994;17:566-574.
23. Guffon N, Vianey-Saban C, Bourgeois J, et al: A new neonatal case of N-acetylglutamate synthase deficiency
treated by carbamylglutamate. J Inher Metab Dis 1995;18:61-65.
25. Hyman SL, Coyle JT, Parke JC, et al: Anorexia and altered serotonin metabolism in a patient with argininosuccinic
aciduria. J Pediatr 1986;108:705-709.
26. Iafolla AK, Gale DS, Roe CR: Citrate therapy in argininosuccinate lyase deficiency. J Pediatr 1990;117:102-105.
27. Jackson AA, Badaloo AV, Forrester T, et al: Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index
of glycine insufficiency in normal man. Brit J Nutr 1987;58:207-214.
28. James MO, Smith RL, Williams RT, Reidenberg M: The conjugation of phenylacetic acid in man, sub-human
primates and some non-primate species. Proc R Soc Lond 1972;182:25-35.
29. Kuchler G, Rabier D, Poggi-Travert F, et al: Therapeutic use of carbamylglutamate in the case of
carbamoylphosphate synthetase deficiency. J Inher Metab Dis 1996;19;220-222.
30. LaBrecque DR, Latham PS, Reily CA, et al: Heritable urea cycle enzyme deficiency. Liver disease in 16 patients.
J Pediatr 1979;94 (4):587-587.
31. Leao M: Valproate as a cause of hyperammonemia in heterozygotes with ornithine-transcarbamylase deficiency.
J Neurol 1995;45:593-594.

1982.
33. Maestri NE, Brusilow SW, Clossold DB, Bassett SS: Long-term treatment of girls with ornithine transcarbamylase
deficiency. N Engl J Med 1996;335:855-859.
34. Maestri NE, Clissold D, Brusilow SW: Neonatal onset ornithine transcarbamylase deficiency: A retrospective
analysis. J Pediatr 1999;134:268-272.
1987;1:1-17.
36. Meites S (ed): Pediatric Clinical Chemistry: Reference Normal Values, ed 3. Washington, DC: AAAC Press, 1989.
37. Melnyk AR, Matalon R, Henry B, et al: Prospective management of a child with neonatal citrullinemia. J Pediatr
1993;122:96-98.
38. Oechsner M, Steen C, Sturenburg HJ, Kohlschutter A: Hyperammonaemic encephalopathy after initiation of
valproate therapy in unrecognized ornithine transcarbamylase deficiency. J Neurol Neurosurg Psychiat
1998;64:680-682.
39. Ohtani Y, Ohyanagi K, Yamamoto S, Matsuda I: Secondary carnitine deficiency in hyperammonemic attacks of
ornithine transcarbamylase deficiency. J Pediatr 1988;112:409-414.
41. Prasad AN, Breen JC, Ampola MG, Rosman P: Argininemia: A treatable genetic cause of progressive spastic
diplegia stimulating cerebral palsy. Case reports and literature review. J Child Neurol 1997;12:301-309.
42. Pridmore CL, Clarke JTR, Blaser S: Ornithine transcarbamylase deficiency in females: An often overlooked cause
of treatable encephalopathy. J Child Neurol 1995;10:396-374.
43. Sanjurjo P, Rodriguez-Soriano J, Vallo A, Rubio V. Neonatal citrullinemia with satisfactory mental development.
Eur J Pediatr 1991;150:730-731.
45. Sewell AC, Bohles HJ, Herwig J, Demirkol M: Neurological deterioration in patients with urea cycle disorders under
valproate therapy - a cause for concern. Eur J Pediatr 1995;154:593-594.
1976.
1983;7:280-288.
48. Snyderman SE, Holt LE, Dancis J, et al: "Unessential" nitrogen: A limiting factor for human growth. J Nutr
1962;78:57-52.
1989;143:828-832.
50. Tamura S, Kawata S, Fukuda K, et al: Effects of glucagons on urinary excretion of urea and on plasma ammonia
level in argininosuccinate synthetase deficiency. J Gastroenterol 1994;29:31-34.
51. Torun B, Chew F: Protein-energy malnutrition. In Shils ME, et al (eds): Modern Nutrition in Health and Disease,
52. Tuchman M, Yudkoff M: Blood levels of ammonia and nitrogen scavenging amino acids in patients with inherited
hyperammonemia. Mol Genet Metab 1999;66;10-15.
53. Vasudevan S, Qureshi IA, Lambert M, et al: Nucleotide pool imbalances in the livers of patients with urea cycle
disorders associated with increased levels of orotic aciduria. Biochem Molec Biol Int'l 1995;35:685-690.
1977;30:1269-1280.
55. Wong LJC, Craigen WJ, O'Brien WE: Post-partum coma and death due to carbamoyl-phosphate synthetase I
deficiency. Ann Int Med 1994;120;216-217.
56. Zeman FJ: Clinical Nutrition and Dietetics, ed 2. New York: MacMillan Publishing Co, 1991.

APPENDICES
Page
Nutrient Composition Tables
APPENDIX 1. Fatty Acid Profile of Infant/Toddler Metabolic Medical Foods........................................A-2
APPENDIX 2. Fatty Acid Profile of Child/Adult Metabolic Medical Foods ............................................A-2
APPENDIX 3. Density of Metabolic Medical Foods..............................................................................A-3
APPENDIX 4. Nutrient Composition of Alimentum ® Protein Hydrolysate Formula With Iron...............A-4
APPENDIX 5. Nutrient Composition of Isomil ® Soy Formula With Iron ..............................................A-5
APPENDIX 6. Nutrient Composition of Similac ® With Iron Infant Formula .........................................A-6
APPENDIX 7. Nutrient Composition of NeoSure ® and Similac ® Lactose Free..................................A-7
APPENDIX 8. Nutrient Composition of Mature Human Milk, Skim Milk, Whole Cow's Milk, and
Whole Egg..........................................................................................................A-8
APPENDIX 9. Nutrient Composition of Polycose ® Glucose Polymers and Pedialyte ® Oral
Electrolyte Maintenance Solution .........................................................................A-9
APPENDIX 10. Nutrient Composition of Selected Vegetable Oils........................................................A-9
APPENDIX 11. Nutrient Composition of Vi-Daylin ® Multivitamin + Iron Drops and Pro-Phree ®
Protein-Free Energy Module with Iron, Vitamins, and Minerals and ....................A-10
APPENDIX 12. Nutrient Composition of Very-Low-Protein Foods per 100 g. .....................................A-11
Recommended Dietary Intakes

APPENDIX 13. Recommended Dietary Intakes (RDIs) for Minerals and Vitamins by Infants .............A-14
APPENDIX 14. Recommended Dietary Intakes (RDIs) for Minerals and Vitamins by Children,
Adolescents, and Adults.....................................................................................A-15
Technical Information
APPENDIX 15. Mathematical Formula for Interconversion of Plasma Amino Acids Between
µmol/L and mg/dL ..............................................................................................A-17
APPENDIX 16. Molecular Weights of Amino Acids ...........................................................................A-17
APPENDIX 17. Selected Laboratory Standards.................................................................................A-18
APPENDIX 18. Estimating Osmolarity of a Medical Food Mixture .....................................................A-20
APPENDIX 19. Approximate Osmolarity of Selected Foods ..............................................................A-21
APPENDIX 20. Potential Renal Solute Load of Medical Food Mixture ...............................................A-22
APPENDIX 21. NDC Numbers for Metabolic Medical Foods .............................................................A-23
Clinical Forms
APPENDIX 22. Diet Guide ................................................................................................................A-24
APPENDIX 23. Evaluation of Mineral/Vitamin Content of Medical Food Mixture ...............................A-25
APPENDIX 24. Diet Diary .................................................................................................................A-26
APPENDIX 25. Directions for Recording the Diet Diary .....................................................................A-27
Supplier Information
APPENDIX 26. Sources of Nutrients and Drugs ................................................................................A-28
APPENDIX 27. Low-Protein Food Suppliers......................................................................................A-29
APPENDIX 28. Products for Prescription Diet Management ..............................................................A-29
© 2001 Ross Products Division A-1

APPENDIX 1. Fatty Acid Profile of Infant/Toddler Metabolic Medical Foods
Fatty Acid Infant/Toddler Metabolic Medical Foods 1, 2

Pro-Phree Cyclinex-1 ® Others 3
g/100 g Pwd % of Energy g/100 g Pwd % of Energy g/100 g Pwd % of Energy
Caprylic (8:0) 0.78 1.38 0.69 1.22 0.60 1.12
Capric (10:0) 0.57 1.01 0.50 0.88 0.44 0.82
Lauric (12:0) 4.17 7.36 3.66 6.46 3.21 6.02
Myristic (14:0) 1.61 2.84 1.41 2.49 1.24 2.32
Palmitic (16:0) 2.20 3.88 1.93 3.41 1.70 3.19
Palmitoleic (16:1) 0.02 < 0.04 0.02 < 0.04 0.01 < 0.02
Margaric (17:0) 0.01 < 0.02 0.01 < 0.02 0.01 < 0.02
Stearic (18:0) 1.53 2.70 1.34 2.36 1.21 2.27
Oleic (18:1) 9.42 16.62 8.28 14.61 7.30 13.69
Linoleic (18:2) 5.49 9.69 5.08 8.96 4.47 8.38
α-Linolenic (18:3) 0.56 0.99 0.51 0.90 0.45 0.84
Arachidic (20:0) 0.08 0.14 0.07 0.12 0.06 0.11
Eicosenoic (20:1) 0.05 0.09 0.04 0.07 0.04 0.08
Behenic (22:0) 0.06 0.11 0.06 0.11 0.05 0.09
Lignoceric (24:0) 0.03 0.05 0.03 0.05 0.02 < 0.04
Nervonic (24:1) 0.02 < 0.04 0.02 < 0.04 0.02 < 0.04
Total saturated 11.04 19.48 9.69 17.12 8.54 16.00
Total monounsaturated 9.51 16.78 8.36 14.76 7.37 13.83
Total polyunsaturated 6.05 10.68 5.59 9.86 4.92 9.22
1
Oil blend: 29% soy, 35% coconut, 36% high-oleic safflower oils
2
Analytical data at manufacture.
3
Glutarex-1, Hominex-1, I-Valex-1, Ketonex-1 , Phenex-1, Propimex-1, and Tyrex -1 Amino Acid Modified Medical
Foods with Iron.
APPENDIX 2. Fatty Acid Profile of Child/Adult Metabolic Medical Foods
Fatty Acid Child/Adult Metabolic Medical Foods 1, 2

Cyclinex-2 Others 3 Phenex2 Flavored
g/100 g Pwd % of Energy g/100 g Pwd % of Energy g/100 g Pwd % of Energy
Caprylic (8:0) 0.48 0.98 0.39 0.86 0.38 0.83
Capric (10:0) 0.35 0.72 0.28 0.61 0.27 0.59
Lauric (12:0) 2.53 5.18 2.08 4.57 2.01 4.41
Myristic (14:0) 0.98 2.00 0.80 1.76 0.77 1.69
Palmitic (16:0) 1.33 2.72 1.10 2.41 1.06 2.33
Palmitoleic (16:1) 0.01 0.02 0.01 0.02 < 0.01 0.02
Margaric (17:0) < 0.01 < 0.02 < 0.01 0.02 < 0.01 0.02
Stearic (18:0) 0.93 1.90 0.76 1.67 0.74 1.62
Oleic (18:1) 5.72 11.70 4.71 10.34 4.55 9.99
Linoleic (18:2) 3.33 6.81 2.75 6.04 2.66 5.84
α-Linolenic (18:3) 0.34 0.70 0.28 0.61 0.27 0.59
Arachidic (20:0) < 0.01 < 0.02 0.04 0.09 0.04 0.09
Eicosenoic (20:1) 0.03 0.06 0.04 0.09 0.04 0.09
Behenic (22:0) 0.04 0.08 0.03 0.07 0.03 0.07
Lignoceric (24:0) 0.02 0.04 0.01 0.02 0.01 0.02
Nervonic (24:1) 0.01 0.02 0.01 0.02 0.01 0.02
Total saturated 6.68 13.66 5.50 12.08 5.32 11.67
Total monounsaturated 5.77 11.80 4.75 10.47 4.61 10.12
Total polyunsaturated 3.67 7.51 3.03 6.65 2.93 6.43
1
Oil blend: 29% soy, 35% coconut, 36% high-oleic safflower oils.
2
Analytical data at manufacture.
3
Glutarex-2; Hominex-2; I-Valex-2; Ketonex-2; Phenex-2, unflavored; Propimex-2; and Tyrex-2 Amino Acid Modified
Medical Foods.
A-2 © 2001 Ross Products Division

APPENDIX 3. Density of Metabolic Medical Foods
Product g/mL Powder

Infant/Toddler
Calcilo XD ® Low-Calcium/Vitamin D-Free Infant Formula With Iron 0.52
Cyclinex® -1 Amino Acid Modified Medical Food With Iron 0.55
Glutarex®-1 Amino Acid Modified Medical Food With Iron 0.59
Hominex®-1 Amino Acid Modified Medical Food With Iron 0.58
I-Valex®-1 Amino Acid Modified Medical Food With Iron 0.58
Ketonex®-1 Amino Acid Modified Medical Food With Iron 0.56
Phenex™-1 Amino Acid Modified Medical Food With Iron 0.56
Pro-Phree ® Protein-Free Energy Module With Iron, Vitamins & Minerals 0.52
Propimex®-1 Amino Acid Modified Medical Food With Iron 0.57
ProViMin ® Protein-Vitamin-Mineral Component With Iron 0.19
RCF® Carbohydrate Free Soy Formula Base With Iron 1.01/mL1
Tyrex®-1 Amino Acid Modified Medical Food With Iron 0.59
Child/Adult
Cyclinex®-2 Amino Acid Modified Medical Food 0.40
Glutarex®-2 Amino Acid Modified Medical Food 0.52
Hominex®-2 Amino Acid Modified Medical Food 0.46
I-Valex®-2 Amino Acid Modified Medical Food 0.51
-
Ketonex® 2 Amino Acid Modified Medical Food 0.54
Phenex™-2 Amino Acid Modified Medical Food, flavored 0.48
Phenex™-2 Amino Acid Modified Medical Food, unflavored 0.47
Propimex® -2 Amino Acid Modified Medical Food 0.54
Tyrex® -2 Amino Acid Modified Medical Food 0.46
1
Concentrated liquid.

APPENDIX 4. Nutrient Composition of Alimentum Protein Hydrolysate
Formula With Iron
Nutrient Ready To Feed
(per 100 mL)
Energy, kcal 68
Protein equiv, g 1.86
1
Amino acids, g 2.07
Arginine, mg 77
Cystine, mg 32
Glycine, mg 50
Histidine, mg 53
Isoleucine, mg 108
Leucine, mg 173
Lysine, mg 163
Methionine, mg 54
Phenylalanine, mg 86
Threonine, mg 88
Tryptophan, mg 25
Tyrosine, mg 29
Valine, mg 140
Carnitine, mg 1.26
Taurine, mg 5.49
Carbohydrate, g 6.9
2
Fat, g 3.75
Linoleic acid, g 1.28
α-Linolenic acid, g 0.066
Minerals
Calcium, mg 71
Chloride, mg/mEq 54/1.5
Copper, mg 0.05
Iodine, µg 10
Iron, mg 1.22
Magnesium, mg 5.1
Manganese, mg 0.005
Phosphorus, mg 51
Potassium, mg/mEq 80/2.0
Selenium, µg 1.86
Sodium, mg/mEq 30/1.3
Zinc, mg 0.51
Vitamins
A, µg RE 61
D, µg 0.76
E, mg α-TE 1.36
K, µg 10
Ascorbic acid, mg 6.1
Biotin, µg 3.0
B6, mg 0.04
B12, µg 0.30
Choline, mg 5.4
Folate, µg 10
Inositol, mg 3.4
Niacin equiv, mg 1.33
Pantothenic acid, mg 0.51
Riboflavin, mg 0.06
Thiamin, mg 0.04
1
Mean values.
2
33% of fat is fractionated coconut oil.

APPENDIX 5. Nutrient Composition of Isomil ® Soy Formula With Iron
Nutrient Concentrate Powder1 Ready To Feed

(per 100 mL) (per 100 g) (per 100 mL)
Energy, kcal 136 516 68
Protein, g 3.32 12.60 1.66
2
Amino acids, g 3.33 12.96 1.67
Arginine, mg 244 970 122
Cystine, mg 36 154 18
Glycine, mg 142 540 71
Histidine, mg 84 334 42
Isoleucine, mg 148 578 74
Leucine, mg 270 1,021 135
Lysine, mg 200 754 100
Methionine, mg 84 319 42
Phenylalanine, mg 176 675 88
Threonine, mg 128 493 64
Tryptophan, mg 42 163 21
Tyrosine, mg 120 464 60
Valine, mg 152 582 76
Carnitine, mg 2.6 9.9 1.3
Taurine, mg 7.6 28.8 3.8
Carbohydrate, g 13.9 52.8 6.96
Fat, g 7.4 28.0 3.69
Linoleic acid, g 1.36 5.16 0.68
α-Linolenic acid, g 0.36 1.37 0.18
Minerals
3
Calcium, mg 142 539 (697) 71
Chloride, mg/mEq 84/2.4 319/9.0 42/1.2
Copper, mg 0.10 0.38 0.05
Iodine, µg 20 76 10
Iron, mg 2.4 9.3 1.2
Magnesium, mg 10 39 5.1
Manganese, mg 0.04 0.15 0.02
3
Phosphorus, mg 101 387 (464) 51
Potassium, mg/mEq 146/3.73 554/14.17 73/1.90
Selenium, µg 2.66 10.1 1.33
Sodium, mg/mEq 60/2.6 228/9.9 30/1.3
Zinc, mg 1.02 3.87 0.51
Vitamins
A, µg RE 122 463 61
D, µg 2.0 7.6 1.0
E, mg α-TE 2.7 10.3 1.36
K, µg 14.8 56.2 7.4
Ascorbic acid, mg 12.2 46.3 6.1
Biotin, µg 6 22.8 3.0
B6, mg 0.08 0.30 0.04
B12, µg 0.6 2.27 0.30
Choline, mg 10.8 41 5.4
Folate, µg 20 76 10
Inositol, mg 6.8 25.8 3.4
Niacin equiv, mg 2.4 9.1 1.2
Pantothenic acid, mg 1.02 3.87 0.51
Riboflavin, mg 0.12 0.46 0.06
Thiamin, mg 0.08 0.30 0.04
1
The weight per level unpacked scoop of Isomil Powder is 8.7 g.
2
Mean values.
3
Amount in parentheses is amount present in Isomil 2 powder/100 g.

APPENDIX 6. Nutrient Composition of Similac ® With Iron Infant Formula
1
Nutrient Concentrate Powder Ready To Feed
(per 100 mL) (per 100 g) (per 100 mL)
Protein, g 2.80 10.83 1.40
2
Amino acids, g 2.88 11.05 1.44
Arginine, mg 82 325 41
Cystine, mg 38 162 19
Glycine, mg 56 217 28
Histidine, mg 66 262 33
Isoleucine, mg 150 573 75
Leucine, mg 288 1,079 144
Lysine, mg 226 895 113
Methionine, mg 70 273 35
Phenylalanine, mg 118 465 59
Threonine, mg 154 583 77
Tryptophan, mg 44 174 22
Tyrosine, mg 116 450 58
Valine, mg 166 641 83
Carnitine, mg 1.4 5.6 0.7
Taurine, mg 8.0 33.0 4.0
Carbohydrate, g 14.6 55.06 7.3
Fat, g 7.30 28.15 3.65
Linoleic acid, g 1.36 5.13 0.68
α-Linolenic acid, g 0.14 0.53 0.07
Minerals
Calcium, mg 106 400 53
Chloride, mg/mEq 88/2.4 332/9.4 44/1.2
Copper, mg 0.12 0.45 0.06
Iodine, µg 8.2 30.9 4.1
Iron, mg 2.4 9.2 1.2
Magnesium, mg 8.2 30.9 4.1
Manganese, mg 0.007 0.023 0.003
Phosphorus, mg 56 211 28
Potassium, mg/mEq 142/3.6 536/13.7 71/1.8
Selenium, µg 4.2 15.8 2.1
Sodium, mg/mEq 32.4/1.4 122/5.3 16.2/0.7
Zinc, mg 1.02 3.85 0.51
Vitamins
A, µg RE 122 459 61
D, µg 2.02 7.62 1.01
E, mg α-TE 1.5 5.8 0.74
K, µg 10.8 41.0 5.4
Ascorbic acid, mg 12.2 46.0 6.1
Biotin, µg 6.0 22.6 3.0
B6, mg 0.08 0.30 0.04
B12, µg 0.34 1.28 0.17
Choline, mg 21.6 81.5 10.8
Folate, µg 20.2 76.2 10.1
Inositol, mg 6.4 24.1 3.2
Niacin equiv, mg 2.16 8.14 1.08
Pantothenic acid, mg 0.60 2.26 0.30
Riboflavin, mg 0.20 0.75 0.10
Thiamin, mg 0.13 0.53 0.07
1
The weight per level unpacked scoop of Similac With Iron Powder is 8.5 g.
2
Mean values.

APPENDIX 7. Nutrient Composition of Similac NeoSure™ Powder and Similac® Lactose Free Powder
1 1
Nutrient NeoSure Powder Similac Lactose-Free Powder
(100 g) (100 g)
Energy, kcal 513 519
Protein, g 13.3 11.1
2
Amino acids, g 13.73 11.75
Arginine, mg 389 384
Cystine, mg 207 87
Glycine, mg 262 226
Histidine, mg 299 298
Isoleucine, mg 688 515
Leucine, mg 1,335 1,128
Lysine, mg 1,105 920
Methionine, mg 336 313
Phenylalanine, mg 522 549
Threonine, mg 769 515
Tryptophan, mg 217 156
Tyrosine, mg 555 580
Valine, mg 743 642
Carnitine, mg 34 10
Taurine, mg 54 42
Fat, g 28.2 28.0
Linoleic acid, g 4.98 5.61
α-Linolenic acid, g 0.54 0.51
Minerals
Calcium, mg 539 436
Chloride, mg/mEq 385/10.9 337/9.5
Iodine, µg 77 47
Iron, mg 9.2 9.4
Magnesium, mg 46 31
Phosphorus, mg 318 291
Potassium, mg/mEq 729/18.7 555/14.2
Selenium, µg 23 15
Sodium, mg/mEq 170/7.4 156/6.8
Zinc, mg 6.2 3.9
Vitamins
A, µg RE 709 468
D, µg 8.99 7.80
E, mg α-TE 12.4 10.5
K, µg 56 42
Biotin, µg 46 23
B6, mg 0.51 0.31
B12, µg 2.06 1.30
Choline, mg 82 83
Folate, µg 128 78
Inositol, mg 31 22
Niacin equiv, mg 13.63 8.05
1
g/scoop 9.6 8.6

APPENDIX 8. Nutrient Composition of Mature Human Milk, Skim Milk, Whole Cow's Milk, and Whole Egg
1 2 2
Nutrient Mature Human Milk Skim Milk Whole Cow's Milk Whole Egg
(per 100 mL) (per 100 mL) (per 100 mL) (per 50 g)
Energy, kcal 72 36 63 74
Protein, g 1.07 3.53 3.39 6.24
3
Amino acids, g
Arginine, mg 45 127 123 375
Cystine, mg 20 33 31 148
Glycine, mg 27 75 72 210
Histidine, mg 24 95 92 147
Isoleucine, mg 58 213 205 341
Leucine, mg 99 346 332 533
Lysine, mg 71 280 269 449
Methionine, mg 22 89 86 195
Phenylalanine, mg 48 171 164 332
Threonine, mg 48 159 154 300
Tryptophan, mg 18 50 47 76
Tyrosine, mg 55 171 164 255
Valine, mg 66 236 227 380
3
Carnitine, mg 1.0 NA 4.0 NA
4
Taurine, mg 5.0 NA 15.0 NA
Carbohydrate, g 7.18 5.02 4.81 0.61
Fat, g 4.56 0.19 3.46 5.01
Linoleic acid, g 0.39 0.005 0.08 0.57
α-Linolenic acid, g 0.05 0.002 0.05 0.02
Minerals
Calcium, mg 34 127 123 24
Chloride, mg/mEq 42/1.2 103/2.90 105/3.0 84/2.4
Copper, mg 0.05 0.010 0.010 0.007
5 3
Iodine, µg 11 1.8 37 13
Iron, mg 0.03 0.04 0.05 0.72
Magnesium, mg 3.5 11 13.9 5.0
Manganese, mg 0.027 0.002 0.004 0.012
Potassium, mg/mEq 53/1.36 172/4.4 156/4 60.5/1.55
Selenium, µg 1.87 2.17 2.06 15.4
Sodium, mg/mEq 18/0.8 54/2.3 50/2.2 63/2.74
Zinc, mg 0.18 0.41 0.39 0.55
Vitamins
A, µg RE 67 63 32 96
D, µg 0.10 1.06 1.03 0.65
E, mg α-TE 1.00 0.04 0.103 0.52
K, µg 0.21 NA 6.5 NA
Ascorbic acid, mg 5.21 1.01 0.97 0.0
Biotin, µg 0.4 1.6 3.65 10.05
B6, mg 0.011 0.04 0.04 0.07
B12, µg 0.047 0.39 0.37 0.50
Choline, mg 9 NA 20.5 264.5
Folate, µg 5.4 5.18 5.16 24
7 7
Inositol, mg 14.97 NA 4.15 4.55
Niacin equiv, mg 0.48 0.92 0.87 1.31
Riboflavin, mg 0.038 0.14 0.17 0.25
Thiamin, mg 0.015 0.04 0.04 0.03
NA = Not available.

References
1. American Academy of Pediatrics Committee on Nutrition: Pediatric Nutrition Handbook, ed 2. Elk Grove Village, IL:
American Academy of Pediatrics, 1985.
2. Posati LP, Orr ML: Composition of Foods: Dairy and Egg Products. Agriculture Handbook No. 8-1. US Dept of
Agriculture, Agricultural Research Service, 1976.
3. Penn D, Dolderer M, Schmidt-Sommerfeld E: Carnitine concentrations in the milk of different species and infant
formulas. Biol Neonat 1987;52:70.
4. Rana SK, Sanders TAB: Taurine concentrations in the diet, plasma, urine, and breast milk of vegans compared
with omnivores. Br J Nutr 1986;56:17.
5. Pennington JAT: Food Values of Portions Commonly Used, ed 15. New York: Harper & Row Publishers, 1989.
6. Scherz H, Kloos G: Food Composition and Nutrition Tables 1981/1982. Stuttgart: Wissenschaftliche,
Verlagsgesellschaft mbH, 1981.
7. Ogasa K, Kuboyama M, Kiyosawa I, et al: The content of free and bound inositol in human and cow's milk. J Nutr
Sci Vitaminol 1975;21:129.
APPENDIX 9. Nutrient Composition of Polycose ® Glucose Polymers and Pedialyte ® Oral Electrolyte
Maintenance Solution
Nutrient Polycose Powder1 Polycose Liquid Pedialyte

(per 100 g) (per 100 mL) (per 100 mL)
Carbohydrate, g 94 50 2.5
Calcium, mg 30 20 0
Chloride, mg/mEq 223/6.3 140/3.9 122/3.5
Phosphorus, mg 12 3 0
Potassium, mg/mEq 10/0.3 6/0.15 78/2.0
Sodium, mg/mEq 110/4.8 70/3.0 103/4.5
1
Approximate weights of Polycose Powder in level, dry US standard household measures:
1 Tbsp = 6g
1/4 cup = 25 g
1/3 cup = 33 g
1/2 cup = 50 g
1 cup = 100 g
APPENDIX 10. Nutrient Composition of Selected Vegetable Oils
1, 2
Nutrient Vegetable Oils
Canola 3, 4 Coconut Peanut 4 Soybean 4 Walnut 4
(per 100 mL) (per 100 mL) (per 100 mL) (per 100 mL) (per 100 mL)
Energy, kcal 825 807 796 802 802
Fat, g 93 93 90 91 91
Linoleic acid, g 19 2 29 46 48
α-Linolenic acid, g 8.7 0 0 6 9.4
1
1 Tbsp = 15 mL.
2
Reeves JB, Weihrauch JL: Composition of Foods: Fats and Oils. Agriculture Handbook No. 8-4. US Dept of
Agriculture: Agricultural Research Service, 1979.
3
Available commercially as Puritan ® Oil, canola oil.
4
Tightly close and refrigerate all oils after opening. Oils containing large amounts of α-linolenic acid oxidize rapidly
and, after oxidation, are no longer bioactive.

APPENDIX 11. Nutrient Composition of Vi-Daylin ® Multivitamin + Iron Drops and
Pro-Phree ® Protein-Free Energy Module with Iron, Vitamins, and Minerals
Nutrient Vi-Daylin Pro-Phree1

Multivitamin + Iron
Drops (per 100 g)
(1 mL)
Energy, kcal 0 510
Protein Equivalent, g 0 trace
Nitrogen-Containing Compounds 3
Carnitine, mg 0 25
Taurine, mg 0 50
Carbohydrate, g 0 65
Fat, g 0 28
Linoleic acid, g 0 2.70
α-linolenic acid, g 0 0.48
Minerals
Calcium, mg 0 750
Chloride, mg/mEq 0 350/9.9
Copper, mg 0 1.45
Iodine, µg 0 80
Iron, mg 10.0 11.9
Magnesium, mg 0 70
Manganese, mg 0 0.70
Potassium, mg/mEq 0 875/22.4
Selenium, µg 0 30
Sodium, mg/mEq 0 250/10.9
Zinc, mg 0 11
Vitamins
A, µg RE 450 600
D, µg 10 7.5
E, mg α-TE 3.4 12.8
K, µg 0 60
Biotin, mg 0 0.08
B6, mg 0.4 0.97
B12, µg 0 6.5
Choline, mg 0 100.0
Folate, µg 0 300.0
Inositol, mg 0 50.0
Niacin,2 mg 8 14.0
Pantothenic acid, mg 0 7.0
Thiamin, mg 0.5 2.1
1
Approximate packed weight of Pro-Phree in level, dry US standard household measures:
1 Tbsp = 7g
1/4 cup = 29 g
1/3 cup = 38 g
1/2 cup = 57 g
1 cup = 107 g
2
Preformed niacin.

APPENDIX 12. Nutrient Composition of Very-Low-Protein Foods per 100 g
Food Protein Fat Energy ARG CYS HIS ILE LEU LYS MET PHE THR TRP TYR VAL
(g) (g) (kcal) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg) (mg)
Aproten ® Foods
Cracker toast 1.7 4.4 398 100 20 40 50 10 80 30 60 60 20 30 70
dp Baking mix, low protein 0.3 9.4 410 20 5 6 4 8 8 1 5 3 3 3 10
dp Chocolate chip cookies 0.8 22.9 497 30 10 10 70 10 20 2 10 20 10 3 10
Pasta, uncooked 0.5 0.9 360 30 9 10 10 50 20 10 20 10 5 10 20
Rusks 0.8 7.2 420 30 10 10 30 50 40 10 30 30 10 20 30
Wheat Starch 0.5 0.1 350 30 9 10 10 50 20 10 20 10 5 10 20
Dietary Specialties
Breads
bread machine mix 0.3 6.0 351 20 5 7 10 20 10 10 10 10 3 10 10
dinner rolls 0.5 3.5 246 30 9 10 20 40 40 10 20 20 7 10 20
rye-wheat bread 0.8 3.0 200 40 10 10 30 50 40 10 30 30 9 20 40
wheat starch bread 0.4 4.4 242 10 8 9 10 20 9 7 10 10 5 10 20
Cheese
imitation 2.2 20.0 267 80 30 50 120 220 160 50 90 120 20 80 80
sauce mix powder 6.0 26.0 482 170 110 110 190 320 460 90 150 370 90 120 260
slices 3.5 26.3 316 120 30 90 170 270 290 80 150 180 40 160 190
Chocolate bon ons 2.2 11.5 436 100 20 50 100 180 130 40 100 90 30 90 140
Chocolate sauce mix 0.2 3.0 375 10 4 3 4 6 6 2 4 4 3 2 5
Cookies
butterscotch 0.6 22.9 500 20 8 10 30 60 40 10 30 20 9 20 40
chocolate tea 0.7 19.0 482 30 10 10 20 60 20 10 30 20 7 20 30
coconut 0.8 23.0 503 60 10 20 30 90 20 10 40 20 4 20 40
ginger 0.3 11.0 412 10 6 8 10 30 6 6 10 9 1 10 10
orange 0.3 20.0 489 10 7 9 10 40 7 7 10 10 1 10 10
Fruit products
cassava chips 1.7 26.7 520 160 30 20 30 40 50 10 30 30 20 20 40
plantain chips 2.4 38.0 571 190 30 110 60 100 110 30 80 60 20 50 80
Graham cracker 0.5 20.3 473 30 9 10 10 30 20 10 20 10 5 10 20
Grains, uncooked
Porridge 0.3 1.0 360 10 6 8 9 20 8 3 10 8 2 10 10
Rice, imitation 0.3 1.0 360 10 6 8 9 20 8 3 10 8 2 10 10
A-11
Pasta, uncooked 0.3 1.0 360 10 6 8 8 20 8 3 10 8 2 10 10

Pizza shells 0.7 5.3 368 30 9 10 20 40 20 9 20 10 5 10 30
Tomato sauce 2.8 2.0 360 270 20 40 40 80 110 20 70 60 20 30 80
Ener-G ® Foods
Breads
mix 0.3 0.1 376 8 7 4 6 10 9 3 6 6 3 2 9
rice 0.3 8.7 325 10 5 7 5 10 10 6 10 10 3 6 10
rice starch 0.4 9.5 334 10 7 8 10 30 20 4 10 10 4 4 20
wheat starch 0.5 5.0 257 10 8 8 10 20 20 4 10 10 4 9 10
Cheese, cheddar or mozzarella 1.9 20.0 279 100 10 80 140 280 220 60 150 110 30 120 180
Cookies
lemon sandwich 0.2 21.0 486 10 4 3 4 6 6 2 4 4 3 2 5
lemon shortbread 0.2 21.5 476 10 2 2 6 10 6 3 8 5 2 7 8
orange shortbread 0.4 19.2 469 10 10 5 10 10 5 3 10 10 10 5 10
Egg replacer 0.1 0.0 375 4 1 1 1 3 3 1 2 1 1 1 3
Flour
potato starch 0.1 0.0 320 7 1 2 2 4 5 1 4 2 1 2 4
rice starch 0.8 0.0 375 40 7 8 20 40 20 10 30 10 6 20 30
tapioca 0.1 0.0 396 10 2 2 2 3 3 1 2 2 2 1 3
Gel mix
banana 0.0 0.0 372 0 0 0 0 0 0 0 0 0 0 0 0
chocolate 0.0 0.0 344 0 0 0 0 0 0 0 0 0 0 0 0
lemon 0.0 0.0 367 0 0 0 0 0 0 0 0 0 0 0 0
lime 0.0 0.0 383 0 0 0 0 0 0 0 0 0 0 0 0
orange 0.0 0.0 361 0 0 0 0 0 0 0 0 0 0 0 0
raspberry 0.0 0.0 370 0 0 0 0 0 0 0 0 0 0 0 0
strawberry 0.0 0.0 372 0 0 0 0 0 0 0 0 0 0 0 0
Ice cream cone 0.1 2.9 396 10 2 2 2 3 3 1 2 2 2 2 3
Pizza shells 1.7 13.6 320 3 7 10 10 20 20 9 10 10 4 5 20
Potato
chips 0.7 49.0 641 40 10 10 20 40 20 6 20 10 10 10 20
mix 0.1 0.0 380 7 1 2 2 4 5 1 3 2 1 2 4
Pumpkin donut 0.8 14.0 304 40 5 10 20 30 30 10 20 20 9 30 30
Waffles 0.2 7.0 248 20 1 8 10 30 10 8 20 10 1 10 20
Kingsmill ® Foods
Cake base 0.3 8.8 353 10 6 6 10 6 5 5 10 7 3 8 10
Cookies
chocolate chip 0.8 20.0 500 30 10 10 20 50 10 10 30 20 9 20 30
orange 0.6 20.5 500 10 10 10 10 30 10 8 20 10 6 10 10
wheat base 1.2 17.0 454 40 20 20 30 70 20 10 40 20 10 30 40
Egg replacer 0.4 1.0 350 10 9 10 10 60 8 10 20 10 2 10 20
Gel dessert, prepared 0.0 0.1 72 0 0 0 0 1 0 0 1 0 0 0 0
Unimix baking mix 0.3 4.9 222 10 6 6 10 10 6 5 10 7 4 10 10
Wheat starch 0.3 0.2 356 10 6 6 10 10 6 5 10 7 3 8 10
LOPROFIN
Baking mix 0.3 0.1 355 10 5 5 7 10 10 4 9 8 4 6 10
Biscuits
chocolate 0.5 27.0 521 3 3 3 5 10 2 3 8 5 2 4 9
sweet 0.4 22.0 496 4 3 3 5 10 2 4 7 5 2 4 9
Crackers 0.4 14.5 444 8 4 4 8 20 6 4 10 7 1 7 10
Pasta, uncooked 0.4 1.0 360 10 7 60 10 20 10 5 10 8 1 6 10
Wafers, cream 0.1 33.0 557 7 4 4 5 10 3 2 7 6 1 3 8
Wel-Plan Foods
Baking Mix 0.3 1.5 339 10 5 5 4 8 5 1 50 6 3 30 10
Pasta, uncooked 0.4 0.7 360 20 7 10 10 30 10 7 10 10 4 10 10
Miscellaneous
Almond Bark
butterscotch 0.0 28.8 529 0 0 0 0 0 0 0 0 0 0 0 0
chocolate 1.2 28.9 518 59 13 18 40 63 52 11 50 41 15 39 62
white 0.0 28.3 526 0 0 0 0 0 0 0 0 0 0 0 0
Prono gel mix 0.0 0.0 390 0 0 0 0 0 0 0 0 0 0 0 0
Schreiber Cheeses, imitation
Cheddar 1.4 15.7 275 40 20 30 70 130 100 20 50 70 10 40 80
slices 4.2 15.8 263 150 100 110 230 410 320 100 180 210 50 170 250
Whitehall Cheeses, imitation 3.7 26.3 300 140 50 90 200 360 300 90 160 180 40 150 210
A-13
APPENDIX 13. Recommended Dietary Intakes (RDIs) for Minerals and Vitamins by Infants
1
Nutrient Recommended Intake for Age
0 to <6 mo 6 to <12 mo
Minerals
Calcium, mg 400 600
Chloride, mEq 8 - 20 11 - 34
Copper, mg 0.5 - 0.7 0.7 - 1.0
Iodine, µg 40 50
2
Iron, mg 10 15
Magnesium, mg 50 75
Manganese, mg 0.5 - 0.7 0.7 - 1.0
Potassium, mEq 9. - 24 11. - 33
Selenium, µg 15 20
Sodium, mEq 5 - 15 11 - 33
Zinc, mg 5 5
Vitamins
A, µg RE 420 400
D, µg 5 5
E, mg α-TE 4 6
K, µg 5 10
Biotin, µg 35 50
B6, mg 0.3 0.6
B12, µg 0.5 1.5
Choline, mg 125 150
Folate, µg 65 80
Inositol, mg 4.8 4.6
3
Niacin equiv, mg 6 8
Pantothenic acid, mg 2 3
Thiamin, mg 0.3 0.5
1
Modified from Food and Nutrition Board: Recommended Dietary Allowances, eds 9 and 10.
Washington, DC: National Academy of Sciences, 1980 and 1989 and Monsen ER: Dietary reference
intakes for antioxidant nutrients: Vitamin C, vitamin E, selenium, and carotenoids. J Amer Diet Assoc
2000;100:637-640.
2
Iron needs of patients with PKU may be greater than RDAs (Gropper S, Acosta PB, Clarke-Sheehan N,
et al: Trace element status of PKU children ingesting an elemental diet. JPEN 1987;11:287).
3
Niacin needs of patients with PKU are greater than RDAs (Lewis JS, Loskill S, Bunker ML, et al:
N-Methylnicotinamide excretion of phenylketonuric children and a child with Hartnup disease before
and after phenylalanine and tryptophan load. Fed Proc 1974;33:666A).

APPENDIX 14. Recommended Dietary Intakes (RDIs) for Minerals and Vitamins by Children, Adolescents, and Adults
Nutrient Recommended Intake for Age 1

1 to < 4 yr 4 to < 7 yr 7 to < 11 yr 11 to < 15 yr 15 to < 19 yr 19 to < 25 yr > 25 yr
Minerals
Calcium, mg 800 800 1,300 1,300 1,300 1,200 1,200
Chloride, mEq 14 - 43 20 - 60 26 - 79 40 - 120 40 - 120 49 - 146 49 - 146
Copper, mg 1.0 - 1.5 1.5 - 2.0 2.0 - 2.5 2.0 - 3.0 2.0 - 3.0 2.0 - 3.0 2.0 - 3.0
Iodine, µg 70 90 120 150 150 150 150
Iron, mg 2,3 15 10 10 18 18 18 18
Magnesium, mg 150 200 250 410 410 410 420
Manganese, mg 1.0 - 1.5 1.5 - 2.0 2.0 - 3.0 2.5 - 5.0 2.5 - 5.0 2.5 - 5.0 2.5 - 5.0
Phosphorus, mg 800 800 1,250 1,250 1,200 1,200 800
Potassium, mEq 14 - 42 20 - 60 26 - 77 39 - 117 39 - 117 48 - 144 48 - 144
Selenium, µg 20 30 40 55 55 55 55
Sodium, mEq 14 - 42 20 - 59 26 - 78 39 - 117 39 - 117 48 - 143 48 - 143
Zinc, mg 10 10 10 15 15 15 15
Vitamins
A, µg RE 400 500 700 1,000 1,000 1,000 1,000
D, µg 5 5 5 5 5 5 5
E, mg α-TE 6 7 11 15 15 15 15
K, µg 15 20 30 45 65 70 80
Ascorbic acid, mg 45 45 45 75 90 90 90
Biotin, µg 65 85 120 120 120 120 120
B6, mg 0.9 1.3 1.6 1.8 2.0 2.2 2.2
B12, µg 2.0 2.5 3.0 3.0 3.0 3.0 3.0
Choline, mg 200 250 375 550 550 550 550
Folate, µg 150 200 300 400 400 400 400
Niacin equiv, mg 4 9 11 16 18 18 19 19
Pantothenic acid, mg 3.0 3.0 4.0 5.0 5.0 5.0 5.0
Riboflavin, mg 0.8 1.0 1.4 1.6 1.7 1.7 1.7
Thiamin, mg 0.7 0.9 1.2 1.4 1.4 1.5 1.5
1
Modified from Food and Nutrition Board: Recommended Dietary Allowances, eds 9 and 10. Washington, DC: National Academy of Sciences, 1980 and 1989 and
Monsen ER: Dietary reference intakes for antioxidant nutrients: Vitamin C, vitamin E, selenium, and carotenoids. J Amer Diet Assoc 2000;100:637-640..
2
Iron needs of patients with PKU may be greater than RDAs (Gropper S, Acosta PB, Clarke-Sheehan N, et al: Trace element status of PKU children ingesting an
elemental diet. JPEN 1987;11:287).
3
Recommended iron intake for men 19 years of age is 10 mg/day.
4
Niacin needs of patients with PKU are greater than RDAs (Lewis JS, Loskill S, Bunker ML, et al: N-Methylnicotinamide excretion of phenylketonuric children and a
A-15
child with Hartnup disease before and after phenylalanine and tryptophan load. Fed Proc 1974;33:666A).
Recommended Daily Intakes (RDIs)
Protein requirements are greater than Recommended Dietary Allowances (RDAs) when L-amino acids are
the primary protein source (2, 7 ). This increased need is due to rapid amino acid absorption and subsequent
oxidation (8, 10), resulting in poor linear growth (5, 16), and lower than normal nitrogen retention (15) and
body protein and nitrogen content of patients fed primarily L-amino acids (3).
Recommended mineral and vitamin intakes suggested for patients with inherited metabolic disorders are
the greatest intakes suggested for each age in the 1980, 1989, and 1998 National Academy of Sciences
RDAs and Dietary Reference Intakes (7, 12, 17). Reasons for choosing the greatest recommended intakes
include reports of inadequate linear growth (5, 16) and poor bone mineralization (11) with Food and
Agriculture Organization/World Health Organization (FAO/WHO) recommended protein intakes (6); greater
than normal energy needs when L-amino acids supply the bulk of protein equivalent (13) and depressed
plasma concentrations of ferritin (4, 14), selenium (9), and zinc (1) when RDAs were achieved with
chemically defined diets.
References
phenylketonuria. Acta Paediatr 1994;Suppl 407:66-67.
3. Allen JR, Baur LA, Waters DL, et al: Body protein in prepubertal children with phenylketonuria. Eur J Clin Nutr
1996;50:178-186.
population at risk for iron-deficiency anaemia and associated cognitive deficits. Eur J Pediatr 1993;152:140-143.
5. Dhondt JL, Largilliere C, Moreno L, Farriaux JP: Physical growth in patients with phenylketonuria. J Inher Metab
Dis 1995;18:135-137.
1985.
8. Gropper S, Acosta PB: Effect of simultaneous ingestion of L-amino acids and whole protein on plasma amino
acids and urea nitrogen concentrations in humans. JPEN 1991;15:48-53.
9. Gropper S, Acosta PB, Clarke-Sheehan N, et al: Trace element status of children with PKU and normal children.
12. Monsen ER: Dietary reference intakes for antioxidant nutrients: Vitamin C, vitamin E, selenium, and carotenoids.
1955;56:231-251.
14. Scaglioni S, Zucotti G, Vedovello M, et al: Study of serum ferritin in 58 children with classic phenylketonuria and
persistent hyperphenylalaninemia. J Inher Metab Dis 1985;8:160.
16. Verkerk PH, van Spronsen JF, Smit GPA, Sengers RCA: Impaired prenatal and postnatal growth in Dutch patients
with phenylketonuria. Arch Dis Child 1994;71:114-118.
17. Yates AA, Schlicker SA, Suitor CW: Dietary reference intakes: The new basis for recommendations for calcium
and related nutrients, B vitamins, and choline. J Amer Diet Assoc 1998;98;699-706.

APPENDIX 15. Mathematical Formula for Interconversion of Plasma Amino Acids Between µmol/L and
mg/dL
Some laboratories report plasma amino acids in mg/dL while others use µmol/L. Converting to either set of
units may be accomplished readily using one of the following mathematical formulas:
µmol/L = mg/dL x 104

MW
mg/dL = MW x µmol/L
104
Where:
MW = molecular weight of amino acid
µmol/L = micromoles per liter
mg/dL = milligrams per deciliter
APPENDIX 16. Molecular Weights of Amino Acids
Amino Acid Molecular Weight

Alanine 89.1
Arginine 174.2
Asparagine 132.1
Aspartic acid 133.1
Citrulline 175.2
Cystine 240.3
Glutamic acid 147.1
Glutamine 146.2
Glycine 75.1
Histidine 155.2
Homocystine 268.4
Hydroxyproline 131.1
Isoleucine 131.2
Leucine 131.2
Lysine 146.2
Methionine 149.2
Ornithine 132.2
Phenylalanine 165.2
Proline 115.1
Serine 105.1
Threonine 119.1
Tryptophan 204.2
Tyrosine 181.2
Valine 117.2

APPENDIX 17. Selected Laboratory Standards
Parameter Age of Patient Status 1

Normal Marginal Deficient
Albumin, plasma (g/dL)
Infants and children < 1 yr 4.00 - 5.00 < 3.50 3.00
1 to < 9 yr 3.50 - 5.00 < 3.50 3.00
> 9 yr 3.50 - 5.00 < 3.50 3.00
Pregnant women Trimester 1 > 4.00 < 3.50 < 3.00
Trimester 2 > 3.75 < 3.25 < 2.75
Trimester 3 > 3.50 < 3.00 < 2.50
Transthyretin (mg/dL) All ages and during pregnancy 22 < 20 < 15
B12, serum, (pg/mL) All ages and during pregnancy > 300 < 260 < 200
Cholesterol (mg/dL)
Infants, children, young 0 < 20 yr 150 - 200 < 150 < 120
adults
Pregnant women Trimester 1 150 - 250 < 150 < 120
Trimester 2 150 - 350 < 150 < 120
Trimester 3 200 - 400 < 200 < 150
Ferritin, plasma (ng/mL)
Infants and children 6 mo to < 2 yr > 30 < 20 < 12
2 to < 6 yr > 40 < 20 < 12
6 to < 12 yr > 50 < 20 < 12
> 12 yr > 50 < 20 < 12
Pregnant women Trimester 1 > 50 < 20 < 12
Trimester 2 > 40 < 20 < 12
Trimester 3 > 30 < 20 < 12
Folate, erythrocyte (ng/mL) All ages and during pregnancy > 200 < 300 < 160 < 120
Hemoglobin (Hgb) (g/dL)
Infants and children 0 to < 5 yr > 11.0 < 11.0 < 10.0
5 to < 8 yr > 11.5 < 11.5 < 10.5
8 to < 12 yr > 12.0 < 12.0 < 11.0
Girls and women > 12 yr > 12.0 < 12.0 < 11.0
Pregnant women Trimester 1 > 12.0 < 12.0 < 11.0
Trimester 2 > 12.0 < 12.0 < 11.0
Trimester 3 > 12.0 < 12.0 < 11.0
Boys and men 12 to < 15 yr > 12.5 < 12.5 < 11.5
15 to < 18 yr > 13.0 < 13.0 < 12.0
>18 yr > 14.0 < 14.0 < 13.0
Hematocrit (Hct) (%)
Infants and children 0 to < 2 yr > 33 < 33 < 30
2 to < 5 yr > 34 < 34 < 32
5 to < 8 yr > 35 < 35 < 33
8 to < 12 yr > 36 < 36 < 33
Girls and women 12 to < 18 yr > 36 < 36 < 33
>18 yr > 37 < 37 < 33
Pregnant women Trimester 1 > 36 < 36 < 33
Trimester 2 > 36 < 36 < 33
Trimester 3 > 36 < 36 < 33
Boys and men 12 to < 15 yr > 37 < 37 < 34
15 to < 18 yr > 38 < 38 < 36
> 18 yr > 40 < 40 < 39
1
Laboratory values vary based on method(s) of sample preparation and analyses. The above standards are considered
guides. Local laboratory standards based on age, gender, and state of health should be developed.

REFERENCES
Ances G, Granados J, Baltazar M: Serum ferritin as an early determinant of decreased iron stores in pregnant women.
South Med J 1979;72:591.
Behrman RE, Kleigman RM, Arvin AA (eds): Nelson Textbook of Pediatrics, ed 12. Philadelphia: WB Saunders Co,
1996.
Deinard AS, Schwartz S, Yip R: Developmental changes in serum ferritin and erythrocyte protoporphyrin in normal
(nonanemic) children. Am J Clin Nutr 1983;38:71.
Fredrickson DS, Goldstein JL, Brown MS: The familial hyperlipoproteinemias. In Stanbury JB, et al (eds): The
Metabolic Basis of Inherited Disease, ed 4. New York: McGraw-Hill Book Co, 1978.
Herbert VD: Folic acid. In Shils ME, et al (eds): Modern Nutrition in Health and Disease, ed 9. Baltimore: Williams &
Wilkins, 1999.
Ingenbleek Y, VanDenSchrieck VD, DeNayer P, DeVisscher M: Albumin, transferrin, and thyroxine binding
prealbumin/retinol binding protein complex in assessment of malnutrition. Clin Chim Acta 1975;63:61.
Lockitch G (ed): Handbook of Diagnosistic Biochemistry and Hematology in Normal Pregnancy. Boca Raton:
CRC Press, 1993.
Ongushina SO, Hussein MA: Plasma thyroxine binding prealbumin as an index of mild protein-energy malnutrition in
Nigerian children. Am J Clin Nutr 1980;33:794.
Soldin SJ, Brugnara C, Hicks JM: Pediatric Reference Ranges, ed 3. Washington, DC: AACC Press, 1999.

APPENDIX 18. Estimating Osmolarity of a Medical Food Mixture
Osmolarity (mosm/L) = A+B+C+D

E
A = g Medical food x osmolarity/g (Appendix 19, p A-21).
B = mL Infant formula or whole cow's milk x osmolarity/mL (Appendix 19, p A-21).
C = mL or g Polycose ® Glucose Polymers or sugar x osmolarity/mL or osmolarity/g (Appendix 19,

p A-21).
D = g Supplemental amino acids x osmolarity/g (mosm/g amino acids = 1.25).
E = mL Total volume of medical food mixture x 0.001 (1 fl oz = 29.57 mL).
Example
Formula 39 g Phenex™-1
305 mL Similac ® With Iron RTF
16 mL Polycose Liquid
Add water to make 540 mL
Osmolarity A = 39 x 2.70 mosm/g = 105.30

B = 305 mL Similac x 0.274 mosm/mL = 83.57
C = 16 mL Polycose x 0.82 mosm/mL = 13.12
Total of A + B + C = 201.99
E = 540 mL x 0.001 = 0.54
Osmolarity = 201.99
0.54
Estimated osmolarity = 374 mosm/L

APPENDIX 19. Approximate Osmolarity of Selected Foods
1
Food Approximate Kcal/fl oz
Osmolality
(mosm/g) 20 24 27 30
(mosm/kg H O)
2
Infant/Toddler
Alimentum, Ready to Feed 0.339/mL -- -- -- --
Calcilo XD 2.02 -- -- -- --
Cyclinex-1 2.21 275 352 408 452
Glutarex-1 2.84 389 476 541 616
Hominex-1 2.75 373 463 527 601
I-Valex-1 2.80 378 470 543 608
Ketonex-1 2.70 366 451 517 588
Phenex-1 2.70 371 453 516 587
Pro-Phree 1.54 205 247 275 305
Propimex-1 2.76 371 470 525 606
ProViMin 2.74 -- -- -- --
RCF, Concentrated Liquid 0.08/mL -- -- -- --
Similac With Iron, Ready to Feed 0.274/mL -- -- -- --
Similac With Iron, Concentrated 0.75/mL -- -- -- --
Liquid
Similac With Iron, Powder 2.84 -- -- -- --
Isomil, Ready to Feed 0.218/mL -- -- -- --
Isomil, Concentrated Liquid 0.60/mL -- -- -- --
Isomil, Powder 2.46 -- -- -- --
Tyrex-1 2.74 380 461 521 593
Child/Adult
Cyclinex-2 4.24 615 784 895 1013
Glutarex-2 5.28 830 1032 1201 1360
Hominex-2 5.18 813 1018 1162 1354
I-Valex-2 5.36 847 1038 1216 1395
Ketonex-2 5.10 805 999 1153 1315
Phenex-2, flavored 4.78 775 938 1070 1216
Phenex-2, unflavored 4.98 782 965 1134 1293
Propimex-2 5.23 834 1018 1172 1354
Tyrex-2 5.13 809 1001 1157 1332
Whole Cow's Milk 0.30/mL -- -- -- --
Polycose Liquid 0.82/mL -- -- -- --
Polycose Powder 1.60 -- -- -- --
Sugar 2.90 -- -- -- --
1
Mixed only with water.

APPENDIX 20. Potential Renal Solute Load of Medical Food Mixture
Because of the limited ability of infants to concentrate urine, fluid may not be retained when an infant is fed
a formula with a high renal solute load; has a restricted water intake; or is suffering from a disease
accompanied by an excessively high temperature. Any of these conditions may result in hypertonic
dehydration if the renal solute load of the infant's formula is not changed.
Approximate the renal solute load of a medical food mixture from its protein, sodium, potassium,
phosphorus and chloride content. Nitrogen (as urea), sodium, chloride, potassium, and phosphorus not
retained for growth or maintenance contribute most of the renal solute load that is excreted with water via
the kidneys. Each gram of protein yields 5.7 mosm. Sodium, potassium, and chloride each yield 1
mosm/mEq. Each milligram of phosphorus yields 0.0323 mosm (mg P ÷ 31). The milliosmoles in the
medical food mixture are estimated as follows:
mosm Potential Renal Solute Load (PRSL) = (mg dietary protein ÷ 175) + mosm (Na + K + Cl + P)
Consider the effect of both insensible and fecal water losses when calculating the effect of renal solute
load on urine concentration. Fever and/or diarrhea may considerably increase these water losses.
Approximate water losses by infants are 10 mL/kg/day in feces and 60 mL/kg/day of insensible loss.
Estimate the urinary concentration by dividing the PRSL contributed to the diet by the water available
for urine formation using the following formula:
mosm RSL/L = mosm in medical food mixture x 1,000

mL medical food mixture - (mL insensible + fecal water losses)
Reference
Fomon SJ, Ziegler EE: Water and renal solute load. In Fomon SJ (ed): Nutrition of Normal Infants. St.
Louis: Mosby, 1993.

APPENDIX 21. NDC Numbers for Metabolic Medical Foods
Pseudo-NDC Number Product Can Size
70074-0037-80 Calcilo XD Powder 400 g
70074-0511-45 Cyclinex-1 Powder 400 g
70074-0511-47 Cyclinex-2 Powder 400 g
70074-0511-41 Glutarex-1 Powder 400 g
70074-0511-43 Glutarex-2 Powder 400 g
70074-0511-17 Hominex-1 Powder 400 g
70074-0511-19 Hominex-2 Powder 400 g
70074-0511-37 I-Valex-1 Powder 400 g
70074-0511-39 I-Valex-2 Powder 400 g
70074-0511-13 Ketonex-1 Powder 400 g
70074-0511-15 Ketonex-2 Powder 400 g
70074-0511-21 Phenex-1 Powder 400 g
70074-0557-56 Phenex-2 Powder, flavored 400 g
70074-0511-23 Phenex-2 Powder, unflavored 400 g
70074-0511-49 Pro-Phree Powder 400 g
70074-0511-33 Propimex-1 Powder 400 g
70074-0511-35 Propimex-2 Powder 400 g
70074-0502-60 ProViMin Powder 150 g
70074-0401-08 RCF (Concentrate) 13 fl oz
70074-0511-29 Tyrex-1 Powder 400 g
70074-0511-27 Tyrex-2 Powder 400 g

APPENDIX 22. Diet Guide
Date: _________/_________/__________
Mo Day Year
Name:_______________________________________________________
Birthdate: __________/__________/__________ Age: __________

Mo Day Year
Length/Height: __________ (cm or in) Weight: _______________ (kg or lb)
Medical Food Mixture Amount _____ _____ _____ _____ Protein Energy
_____________________ _______ g ______ ______ ______ ______ _______ _______
_____________________ _______ g ______ ______ ______ ______ _______ _______
_____________________ _______ g/Tbsp ______ ______ ______ ______ _______ _______
_____________________ _______ g/Tbsp ______ ______ ______ ______ _______ _______
_____________________ _______ mL ______ ______ ______ ______ _______ _______
_____________________ _______ mL ______ ______ ______ ______ _______ _______
(_____________ mg/mL)
Add water to make _______________________ mL (__________________ fl oz).
Food List Servings
Breads/Cereals _______ ______ ______ ______ ______ _______ _______

Fats _______ ______ ______ ______ ______ _______ _______
Fruits _______ ______ ______ ______ ______ _______ _______
Vegetables _______ ______ ______ ______ ______ _______ _______
Free Foods A _______ ______ ______ ______ ______ _______ _______
Free Foods B _______ ______ ______ ______ ______ _______ _______
Total per day ______ ______ ______ ______ _______ _______
Total per kg ______ ______ ______ ______ _______ _______
Comments:
__________________________________________
Nutritionist

APPENDIX 23. Evaluation of Mineral/Vitamin Content of Medical Food Mixture
Nutrient Medical Food(s) Total % RDI RDI

Amount
Name of Product(s)
Amount of Product(s) g g mL
Minerals
Calcium, mg
Chloride, mEq
Copper, mg
Iodine, µg
Iron, mg
Magnesium, mg
Manganese, mg
Phosphorus, mg
Potassium, mEq
Selenium, µg
Sodium, mEq
Zinc, mg
Vitamins
A, µg RE
D, µg
E, mg α-TE
K, µg
Biotin, µg
B6, mg
B12, µg
Ascorbic acid (C), mg
Choline, mg
Folacin, µg
Inositol, mg
Niacin, mg NE
Pantothenic acid, mg
Riboflavin, mg
Thiamin, mg
Carnitine, mg
Taurine, mg

APPENDIX 24. Diet Diary
Name:________________________________________________________________________________
Date of Specimen: _______/_______/_______ Time of Specimen: ________1 Time of Last Meal:

_________1
Mo Day Year
Date of Birth: _______/_______/_______ Weight: _______/_______ (lb/oz) Height: __________ (in)

Mo Day Year
Recorded By: ____________________________________________________
Please record below the food eaten for 3 consecutive days before obtaining a blood specimen.
Medical Food Amount Mineral and/or Vitamin Supplements
g Kind:
g Amount:
mL
mL
Tbsp
Add water to make ____________________ mL (_______________ fl oz).
Spaces Below for Clinic Use

1
Time Foods or Liquids Eaten Protein Energy
Totals
Remarks:
Patient's appetite today was: ¨ Better Than Usual ¨ Usual ¨ Poor
Patient was ill today: ¨ Yes ¨ No If yes, describe:_______________________________
If ill, was medication required? ¨ Yes ¨ No If ill, what was thermometer reading?________________
If yes, name and amount of medication
prescribed:________________________________________________________
Did patient regurgitate food or formula? ¨ Yes ¨ No
Does patient have diarrhea? ¨ Yes ¨ No
1
Record in 24-hour clock (1:00 PM = 13:00)

APPENDIX 25. Directions for Recording the Diet Diary
For greatest accuracy, weigh food on a scale that reads in grams. All measures are level.
1. Use US Bureau of Standards approved measuring cups and spoons for all servings. All measurements
should be level.
2. Measuring utensils needed:

a. 1 set standard measuring spoons
b. 1 set standard measuring cups for nonliquid foods
c. 1 standard glass measuring cup for liquids
d. 1 quart measuring pitcher
e. 1 standard ruler
3. Equivalent measures are:

3 tsp = 1 Tbsp
16 Tbsp = 1 cup
1 fl oz = 2 Tbsp
1 jar 1st ® Fruits and Vegetables = 4 1/2 oz = 9 Tbsp
1 jar 2nd ® and 3rd ® Fruits and Vegetables = 7 1/2 oz = 15 Tbsp
4. At the time it is eaten, record the exact amount of all medical food mixture and beikost or table foods for
3 days before obtaining a blood specimen.
5. Record the following on the Diet Diary form:

a. Prescription for the medical food mixture.
b. Medical food mixture.
1) Amount consumed in mL or fl oz.
c. Beikost (Baby foods).
1) Amount of fruit juice consumed in fluid ounces; the amount of baby fruits in level tablespoon
or teaspoons.
2) Vegetables in level tablespoons or teaspoons.
3) Dry cereals in tablespoons; cooked or jarred cereals in tablespoons.
4) Brand name of foods used.
d. Table foods.
1) Dry and cooked cereals in level cups or tablespoons. List brand name of cereal.
2) Amount of raw fruit consumed as number and size - small, medium, or large - with
approximate measurements such as 2-1/2" x 2".
3) Canned or frozen fruits in cup portions.
4) Cooked vegetables in cup portions or number and length of spears (broccoli and asparagus).
5) Raw vegetables consumed as number and size, such as 2, 4" carrot sticks.
6) Fats in level teaspoons or tablespoons, including those used in cooking. Be sure to use the
correct label, that is butter for butter, margarine, corn oil, etc.
7) Size of portion of desserts and recipes used.
8) List exact number or amount of Free Foods eaten.
9) List amount of each ingredient in mixed dishes unless a standard recipe has been given
previously.
6. Contact your nutritionist before using any food not included on the food list provided.

APPENDIX 26. Sources of Nutrients and Drugs
L-Amino Acids NTBC

Ajinomoto, USA, Inc. Rare Disease Therapeutics, Inc.
Amino Acid division 1101 Kermit Drive
4020 Ajinomoto Drive Suite 608
Raleigh, NC 27610 Nashville, TN 37217-2126
(919) 325-1400; 1404 (615) 399-0700
FAX (919) 325-1420 FAX (615) 399-1217
Jo Mar Laboratories Parenteral Amino Acid Solutions. Designed for specific

251-B E Hacienda Avenue inherited metabolic disorders.
Campbell, CA 95008-6622
(800) 538-4545 Eastern Region
Pharmacy Manager
D-Biotin Coram Health Care
Mericon Industries, Inc. (610) 296-4446
8819 North Pioneer Road
Peoria, IL 61615 Western Region
(309) 693-2150 Pharmacy Manager
FAX: (309) 693-2158 Coram Health Care
(651) 452-5600
Betaine (Cystadane™)
Chronimed, Inc. PharmaThera
13911 Ridgedale Drive 1785 Nonconnah Blvd
Minnetonka, MN 55305 Suite 118
(800) 900-4267 Memphis, TN 88132
(901) 348-8200
(800) 767-6714
L-Carnitine Oral Riboflavin, Oral Thiamin

Sigma Tau Pharmaceuticals, Inc. Nature's Bounty, Inc.
800 South Frederick Avenue 90 Orville Drive
Suite 300 Bohemia, NY 11716
Gaithersburg, MD 20877 (516) 567-9500
(800) 447-0169 (800) 645-5412
Liposyn II Sodium Phenylacetate, Sodium Phenylbutyrate (Ucyclyd)

Abbott Laboratories Ucyclyd Pharma
North Chicago, IL 60064 8125 North Hayden Road
(800) 633-9110 Scottsdale, AZ 85258-2463
(602) 667-3914
MCT Oil (Fractionated Coconut Oil) (888) 829-2593 (24 hours, 7 days week)
Mead Johnson Nutritionals
Evansville, IN 47721-0001
(812) 429-6399

APPENDIX 27. Low-Protein Food Suppliers
Low-Protein Breads, Baking Mixes, Crackers, Cookies, and Pastas
Ener-G ® Foods, Inc Med-Diet™ Laboratories Inc

6901 Fox Ave, S 3050 Ranchview Ln
PO Box 24723 Plymouth, MN 55447
Seattle, WA 98124 (612) 550-2020
(206) 767-6660 (800) 633-3438 (out of state)
Kingsmill Foods Co, Ltd

1399 Kennedy Rd, Unit 17
Scarborough, Ontario
Canada M1P 2L6
(416) 755-1124
APPENDIX 28. Products for Prescription Diet Management
Computer Software Scales That Read in Grams
Amino Acid Analyzer © Pelouze Scales Co

Metabolic Diseases, RP3-2 PO Box 1058
Ross Products Division Evanston, IL 60204
Abbott Laboratories (800) 654-8330
625 Cleveland Avenue (708) 328-8330
Columbus, OH 43215 Order Digital Scale Model RD 5
(614) 624-7648; (614) 624-7516 Current List price: $99.00 (battery operated)
(800) 986-8755
This software contains data for approximately 2,000 foods, including Ross medical foods for inherited
metabolic disorders and low-protein foods. Data were derived from the US Department of Agriculture and
other sources. Nutrient intakes are compared to RDIs for age where available. The software can be used to
calculate the following nutrients: protein; fat; carbohydrate; cholesterol; energy; the amino acids arginine,
cystine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, tyrosine, and
valine; the minerals calcium, copper, iron, magnesium, phosphorus, potassium, and zinc; and the vitamins
A, B6, B12, C, folacin, niacin, pantothenic acid, riboflavin, and thiamin.
Metanova™ Metabolic Diet Planner is software that helps plan diets and evaluate nutrients in the medical
food mixture for patients with PKU. Order from:
Metabolic Diseases
Ross Products Division, RP3-2
Abbott Laboratories
Columbus, OH 43215
(614) 624-7648; (614) 624-7516
(800) 986-8755

INDEX
A
Abdominal pain, 338 Arginine, xi, xvi, 209-211, 213-215, 326, 327, 379-387,
Abetalipoproteinemia, xv 406, 418-422, 427
Abnormal electroencephalograms, 2 Arginine deficiency, 419, 420
Abnormal metabolites, 233, 351, 352 Argininemia, xvi
Acetoacetic acid, 103, 111, 326, 350 Argininosuccinate, 419
Acetoacetyl-CoA thiolase, 124, 125 Argininosuccinic acid, 418
Acetoacetyl-CoA, 123 Argininosuccinic acid lyase, xvi, 418, 419
Acetyl-CoA, 103, 123, 279, 325, 350, 418 Argininosuccinic acid lyase deficiency, 419-421
N-Acetylglutamate synthetase, 418-420 Argininosuccinic acid synthase, xvi, 210, 418, 419
N-Acetylglutamate synthetase deficiency, xvi, 421 Argininosuccinic acid synthase deficiency, 418, 420,
N-Acetylglutamine, 418 421, 426
N-Acetyllysine, 210 Argininosuccinic aciduria, xvi, 419
N-Acetyltyrosine, 63, 65, 68 Arrhythmia, 351
Acylcarnitine, xv, 166, 356 Arteriosclerosis, 296
Acyl-CoA dehydrogenase, 350 Ascites, 313, 314
Acylglycine, 351 Asparagine, xv, 325, 327
Adenosylcobalamin, xi, 230 Aspartic acid, xv, 325-327, 418, 420
S-Adenosylmethionine, 137 Ataxia, 63, 64, 123, 166, 281, 406
Adenosyltransferase, xiii Atherosclerosis, 296, 338
Adipic acid, 197 Attention deficit disorder, 351
Alanine, xiv, 77, 80, 210, 279-282, 325, 326, 406, 407
Alanine aminotransferase, 325 B
Albumin, 8, 38, 55, 68, 78, 81, 111, 126, 129, 144, Benzoic acid, 114, 421
172, 173, 201, 214, 224, 234, 237, 266, 285, ß-1-4-linkages, 263
302, 316, 329, 341, 350, 356, 370, 384, 411, 425 ß-Adrenergic blocking agents, 343
Albuminuria, 262 ß-Galactosidase, 264
Aldolase B, xiv, 313, 314 ß-Hydroxybutyric acid, 111, 326, 350
Alimentum, xiii, 12, 58, 70, 87, 117, 133, 148, 178, ß-Ketoacyl-CoA, 123
216, 226, 243, 332, 373, 387, 414, 429, A-4 ß-Ketothiolase, 123
Alkaline phosphatase, 370 ß-Ketothiolase deficiency, xii, 123, 134
Alloisoleucine, 75, 77, 80, 104 Betaine, xiii, 137-139, 141, 142, 145, 146
Alopecia, 104, 107 Betaine-homocysteine methyltransferase, 137
α-1, 4-Glucan α-1, 4-glucan 6-glucosyltransferase, xiv Biopterin, 2
α-Galactosidase, 264 Biopterin synthetic defects, xi
Biotin, xi, xiv, 230, 231, 234, 325, 327
α-Ketobutyrate, 138
Biotinidase deficiency, xi, 325
α-Ketoisocaproic acid, x
Bleeding diatheses, 419
α-Ketoisovaleric acid, x Bleeding tendency, 140, 313, 314
α-Keto-β-methylvaleric acid, x Brain swelling, 419
α-Methylacetoacetic acid, 124 Branched-chain amino acids, xii, 74-82, 85, 87, 88, 91,
α-Methylacetoacetyl-CoA, 123 125, 128, 130, 172
α-Methyl-ß-hyroxybutyric acid, 124 Branched-chain-α-ketoacid dehydrogenase complex,
Alveolar proteinosis, 209 xi, xii, 74-77, 103
Amino Acid Analyzer, ix Branched-chain-α-ketoacid dehydrogenase complex
Aminoaciduria, 4 deficiency, 103
2-Aminoadipic acid, 166, 168 Branched-chain-α-ketoacids, x, 75, 77, 78
Amylo-1, 6-glucosidase, xiv Butanone, 124
Anemia, 4, 75, 78, 231, 238, 314, 371
Anorexia, 52, 65, 104, 169, 231, 238, 280, 326, 366, C
407, 420 Calcilo XD, xvi, 366, 368-370, 372, 374, A-3
Antiepileptic medication, 283 Calcitriol, 367, 368
Apnea, x, 74, 75, 220, 231, 281, 406, 419 Calcium, xvi, 263, 265, 367, 368, 370, 372, 373
Apo B, xv Calcium propionate, 234
Apo E2, xvi N-Carbamylglutamate, xvi, 420-422
Apolipoprotein C-II, xv, 338 Carbamylphosphate, 418
Apolipoprotein C-II deficiency, 338 Carbamylphosphate synthetase, 406, 418-420
Arabinogalactans, 263 Carbamylphosphate synthetase deficiency, xvi, 421,
Areflexia, 231 427
Arginase, xvi, 418, 419 Carbidopa, 1
Arginase deficiency, 419, 420
I-1 © 2001 Ross Products Division
Cardiac arrest, 103 Developmental delay, 107, 167, 231, 279, 351, 366,
Cardiac defect, 33 406, 419
Cardiomyopathy, 123, 197, 231, 351 Dextromethorphan, 220, 221
Carnitine, xi, xii, xiii, xiv, xv, xvi, 104-109, 111-114, Diarrhea, 49, 50, 78, 103, 200, 262, 263, 298, 299,
123, 124, 126, 127, 129, 168-175, 196-199, 201, 313, 314, 328, 331, 350, 353, 354
202, 221, 222, 224, 232, 234, 235, 238-240, 281- Diazepam, 220, 221
283, 285, 286, 351-354, 356-358, 407, 420 Dicarboxylic aciduria, 351, 355
Carnitine-acylcarnitine translocase deficiency, xv Dichloroacetate, 280-283
Carnitine palmitoyl transferase type I, 350 Diet Diary, 26, 27
Carnitine palmitoyl transferase type II, 350 Diet Guide, 6, 37, 44, 53, 66, 80, 109, 128, 143, 171,
Cataracts, 262, 263, 264, 379, 380 200, 205, 212, 222, 235, 265, 284, 291, 301,
Central nervous system hemorrhage, 103 309, 316, 322, 328, 334, 340, 346, 347, 354,
Cerebral atrophy, 280 361, 369, 375, 383, 409, 423, A-24
Cerebral palsy, 351 Dietary Reference Intakes, vii
Cholesterol, xv, xvi, 78, 125, 140, 169, 233, 234, 297, Dihydropteridine reductase, xii, 2
302 Dinitrophenylhydrazine, 81
Cholesterol granulomas, 209, 210 Dislocated lenses, 138
Choline, 138, 220 Diuretics, 343
Chordee, 197 Dizziness, 286, 314
Choreoathetosis, 166, 167, 169, 406 Dodecanedioic acid, 197
Chylomicronemia, 338, 339, 343-345 DOPA, 1
Cirrhosis, xiv, 49, 207, 314 Dysarthria, 174
Citric acid, xv, 282, 325-328, 336, 421, 422, 426, 427 Dysmorphia, 33, 197, 281
Citrulline, xiii, xvi, 209-213, 215, 326, 387, 407, 408, Dysphagia, 174
411-413, 418, 420-422, 426-428 Dysplasia, 196
Citrullinemia, xvi, 325, 419 Dyspnea, 105
Coagulation factors, 314, 315, 406 Dystonia, 140, 231
Coagulopathy, 314
Cobalamin, 230 E
Cobalamin reductase, xiii Eczema, 2, 3
Cognitive delay, 281 Edema, 313, 314
Cognitive impairment, 279 Electron transfer flavoprotein, 196, 197
Coma, x, 104, 105, 123, 167, 221, 231, 314, 326, 350, Electron transfer flavoprotein deficiency, 196
351, 406, 419 Electron transfer flavoprotein ubiquinone
Congenital anomalies, 33 oxidoreductase, 197
Constipation, 40, 174, 280, 281, 282 Electron transfer flavoprotein ubiquinone
Convulsions, 105, 167, 314, 419 oxidoreductase deficiency, 196
Corneal de-epithelialization, 233 Encephalopathy, 105, 167
Cornstarch, xiv, 202, 298-304, 327, 328, 331, 353, 358 Enoyl-CoA hydratase, 350
Cortical atrophy, 221 Epimerase, xiv
Creatine, 137, 379, 406 Epimerase deficiency, xiv
Cyanocobalamin, 408, 409, 421-423 Epinephrine, 137
Cyanosis, 105 Eruptive xanthomas, 338
Cyclinex, xvi, 379, 382-386, 402, 406-410, 412, 413, Essential fatty acid deficiency, 352, 355
418, 422-424, 426-428, A-3 Essential fatty acids, xv, 198, 299, 327, 339, 352, 353,
Cystathionase, 138 355, 358
Cystathionine ß-synthase, xi, xiii, 138-140 Estrogen, 343
Cystathionine ß-synthase deficiency, 138, 139 Ethylmalonic acid, 197
Cystathioninuria, 138 Ethylmalonic-adipic aciduria, 197
Cysteine, 138 Extrahepatic lipoprotein lipase, xv
2-L-Cysteinyl 5-1,4-dihydroxycyclohexenyl-5, 1-acetic Eye lenses, 262
acid, 63
Cystine, xi, xiii, 139-142, 144-147, 420 F
Failure to thrive, 3-5, 50, 52, 63, 65, 75, 78, 123, 126,
D 140, 141, 169, 174, 209-211, 222, 230, 231, 233,
Dehydration, 7, 54, 67, 80, 104, 105, 110, 128, 143, 234, 262, 263, 281, 282, 313, 314, 351, 381,
172, 174, 200, 213, 223, 230, 231, 236, 266, 408, 421
280, 282, 285, 301, 329, 341, 355, 370, 383, Fanconi syndrome, 49, 50
410, 424, A-22 Fasting chylomicronemia, 338, 345-348
Delayed neurologic development, 326 Fatty acid metabolism, 406
δ-Aminolevulinic acid, x, xi, 49, 51 Fatty acid oxidation, 123
δ-Aminolevulinic acid dehydratase, x, 49, 51 Fatty acid oxidation defects, 351, 353, 358
Fatty acids, 202, 330, 342, 350, 355, 356, 358
© 2001 Ross Products Division I-2
Febrile illness, 11, 57, 69, 75, 84, 114, 132, 147, 169, Glutamic acid, xv, 327
175, 202, 215, 225, 240, 267, 330, 343, 358, Glutamine, xv, 325-327, 379, 384, 406-408, 410-412,
413, 428 422, 424, 425, 428
Ferritin, vii, 8, 38, 55, 68, 81, 111, 129, 130, 144, 173, Glutarex, xiii, 166, 168, 170-173, 175, 177, A-2, A-3
201, 210, 212, 214, 224, 238, 266, 267, 286, Glutaric acid, 166-169, 173, 197
302, 316, 329, 341, 356, 370, 371, 384, 411, 425 Glutaric aciduria type I, xiii, 166, 167, 169, 170, 174-
Ferrous sulfate, 8, 38, 55, 68, 81 111, 129, 144, 173, 176, 192
201, 224, 238, 266, 286, 302, 316, 329, 341, Glutaric aciduria type II, xiii, 196, 197, 202, 204-206
356, 371, 384, 411, 425 Glutarylcarnitine, 167
Fetal damage, 33 Glutaryl-CoA dehydrogenase, xiii, 166, 167
Fibrosis, 314 Glutaryl-CoA dehydrogenase complex, 166
Fishy odor, 169, 234 Glutathione synthesis, 428
Fissures at corners of mouth, 78, 125, 233 Glycine, xi, xii, xiii, 104-109, 112, 113, 173, 197-199,
Folate, xiii, 8, 35, 37, 38, 75, 138, 139, 141, 142, 144- 210, 220, 221, 223, 232, 233, 236, 351, 353,
146, 220, 223, 316, 317, 408, 409, 421-423 354, 357, 358, 420, 421, 425
Fractionated coconut oil, xv, 351 Glycine deficiency, 428
Fructoaldolase, 314 Glycine-N-transacylase, xi
Fructoaldolase B deficiency, 313 Glycogen storage disease type I, 296-298, 301-303,
Fructose, xiv, 298, 299, 306, 313-320 305, 309, 310
Fructose intolerance, 314 Glycogen storage disease type Ia, xiv, 296
Fructose-1-phosphate, 313 Glycogen storage disease type Ib, xiv, 296, 297, 303
Fructose-1-phosphate aldolase, 313 Glycogen storage disease type Ic, 296, 297
Fumarate, 418 Glycogen storage disease type Id, 296, 297
Fumarylacetoacetate, 49 Glycogen storage disease type III, xiv
Fumarylacetoacetate hydrolyase, xii, 49-51, 64 Glycogen storage disease type IV, xiv
Glycogen storage disease type V, xiv
G Glycogenolysis, 313
Galactans, 263 Glycoproteins, 279
Galactitol, 262, 264, 266 Gout, 296
Galactokinase, 262-264, 266 Growth failure, 198, 223, 327, 339, 352
Galactokinase deficiency, xiv, 262, 263, 266 Gyrate atrophy of the choroid and retina, xvi, 379-381,
Galactolipids, 263 403
Galactonate, 262
Galactoproteins, 263 H
Galactose, xiv, 262-268, 270, 273, 298, 299, 306 H4 biopterin, 2
Galactose-1-phosphate, 262-264, 266 H4 biopterin deficiency, 1
Galactose-1-phosphate uridyltransferase, 262, 263 Hair loss, 4, 52, 65, 78, 107, 126, 141, 169, 211, 222,
Galactose-1-phosphate uridyltransferase deficiency, 233, 282, 381, 408, 421
xiv, 262-264, 266 Hawkinsinuria, 50, 63
Galactose toxicity, 262, 263 Hematemesis, 123, 124
Galactosemia, 262, 263, 265, 268-270, 274, 275 Hematologic abnormalities, 104, 209
γ−Aminobutyric acid, 166 Hematophagocytic lymphohistiocytosis, 209
Gastrostomy tube feeding, 174, 237, 238 Hepatic adenomas, 296
Glossitis, 234 Hepatic glycogen metabolism, 296
Glucagon, 313, 419 Hepatic lipoprotein lipase, xvi
Gluconeogenesis, 313, 325 Hepatoma, 50, 51, 56
Glucose, viii, xi, 76, 77, 105, 106, 123-125, 168, 198, Hepatomegaly, 105, 167, 197, 209, 263, 296, 297,
200, 202, 231, 232, 268, 279, 281, 286, 296, 313, 314, 326, 338, 351
297, 298, 299, 301-304, 314, 315, 326, 331, 352, Hepatosplenomegaly, 50, 210, 338
353, 358 Hereditary fructose intolerance, xiv, 313, 314, 317,
Glucose-6-phosphatase deficiency, 297 321-323
Glucose-6-phosphatase, xiv, 296, 297 Herpetiform dendritic ulcers, 64
Glucose-6-phosphate, 297 Hippuric acid, 421
Glucose-6-phosphate translocase, 296, 297 Hominex, xiii, 137, 140, 142-147, 162, A-2, A-3
Glucose-6-phosphate transport, xiv Homoargininuria, 210
Glucose-6-phosphate-6-phosphate, 298 Homocitrulline, 406
Glucose transport protein, 279, 281 Homocitrullinuria, 210
Glucose transport protein deficiency, xiv, 279, 281, Homocysteine, 137-139, 141, 144
283, 284 Homocystine, 137, 139-141, 144
Glucosuria, 314 Homocystinemia, 138
GLUT7 transport protein, 297 Homocystinuria, xi, xiii, 137-139, 147, 148, 163
Glutaconic acid, 166, 168 3-Hydroxy-3-methylglutaric acid, 111
Glutamate, 220, 379, 406, 418
3-Hydroxy-3-methylglutaric aciduria, xiii, 105, 106, Hypotonia, 52, 65, 75, 103, 105, 166, 167, 197, 209,
111, 113 210, 220, 230, 279, 281, 326, 406, 419
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency, 103,
105-109, 112 I
3-Hydroxyacyl-CoA dehydrogenase, 350 Idiopathic hypercalcemia, xvi, 366, 367
3-Hydroxyacyl-CoA dehydrogenase deficiency, 351 Imipramine, 220, 221
2-Hydroxyadipic acid, 166, 168 Infection, viii, 11, 57, 62, 69, 78, 84, 104, 108, 114,
3-Hydroxy-CoA dehydrogenase, 350 115, 123, 126, 147, 175, 196, 202, 211, 213,
Hydroxycobalamin, xiii, 230, 231 215, 222, 230, 231, 240, 268, 303, 317, 330,
2-Hydroxyglutaric acid, 197 343, 350, 352, 358, 408, 410, 411, 413, 419,
3-Hydroxyglutaric acid, 166, 168 421, 424
5-Hydroxyhexanoic acid, 197 Infertility, 263
3-Hydroxyisobutyric acid dehydrogenase, xii Inflammatory bowel disease, 296
3-Hydroxyisobutyric aciduria, xii Interstitial lung disease, 210
3-Hydroxyisovaleric acid, 103, 110, 111, 197 Intracranial pressure, 262
p-Hydroxyphenyl, 68, 71 Intractable seizures, 220, 279-284, 286
p-Hydroxyphenylpyruvic acid dioxygenase, 49, 63-65 Intragastric infusion, 300, 301
3-Hydroxypropionate, 231, 233 Intravascular thromboses, 138
Hyperactivity, 2 Irregular respiration, 75
Hyperaminoaciduria, 262, 314 Irritability, 78, 107, 126, 169, 234, 314, 326, 366, 406,
Hyperammonemia, 103-105, 114, 197, 198, 209-211, 419
213, 215, 230, 231, 325, 381, 384, 406, 408, Isobutrylglycine, 197
410, 413, 418, 419, 421, 424, 428 Isobutyric acid, 197
Hyperbilirubinemia, 314 Isoleucine, x, xi, xii, xiii, xiv, 74, 76-79, 81-83, 85, 104,
Hypercalcemia, 366, 367, 373, 375, 376 107, 123-127, 129-131, 133, 197, 198, 230-239,
Hypercholesterolemia, 296, 297 243, 244, 247
Hyperglycinemia, 124, 172, 226, 230, 231 Isomil, vii, xiii, xiv, xvi, 12, 58, 70, 87, 117, 133, 148,
Hyperkeratosis, 64 178, 213, 216, 223, 226, 243, 262, 263, 265,
Hyperlacticacidemia, 231, 297 267, 268, 274, 332, 373, 387, 414, 429, A-5
Hyperlipidemia, 296, 420 Isoretinoin, 343
Hyperlipoproteinemia type I, xv Isovaleric acid, xi, 103, 104, 111, 197
Hyperlipoproteinemia type IIa, xvi Isovaleric acidemia, xi, xii, 103, 104, 110, 112, 119
Hyperlipoproteinemia type IIb, xvi Isovaleryl-CoA dehydrogenase, xii, 103
Hyperlipoproteinemia type III, xvi Isovaleryl-CoA dehydrogenase deficiency, 103, 104
Hyperlysinemia, 325 Isovalerylglycine, xi, 103, 110, 197
Hypermethioninemia, xiii, 137, 138 I-Valex, xii, xiii, 103, 105, 106, 108-114, 116, A-2, A-3
Hypernornithinemia - hyperammonemia -
homocitrullinuria syndrome, xvi, 406, 41-415, J
419 Jaundice, 50, 262, 263, 313, 314
Hyperornithinuria, 380, 381, 406
Hyperphenylalaninemia, 1, 2 K
Hyperpnea, 105 Ketamine, 220
Hypertonia, 75, 231 Ketoacidosis, 231
Hypertriacylglycerolemia, 280, 296-298 Ketoacids, 81, 111, 129, 133, 237
Hyperuricemia, 296, 297 3-Ketoacyl-CoA thiolase, 350
Hyperventilation, 231 2-Ketoadipic acid, 166, 168
Hypoalbuminemia, 173, 280, 282, 314 2-Ketoadipic aciduria, xiii, 166, 167, 176, 178, 192
Hypobetalipoproteinemia, xv 2-Ketoadipic dehydrogenase, xiii, 166, 167
Hypocalcemia, 104 Ketogenesis, 282, 283
Hypocarnitinemia, 281 Ketogenic diet, xiv, xv, 279-282, 286, 287, 291, 292
Hypocholesterolemia, 314 Ketones, 125, 234, 240, 280, 281, 285, 350
Hypodensity of myelin, 221 Ketonex, xii, 74, 76, 77, 79-84, 86, 124, 125, 127-132,
Hypoglycemia, 105, 167, 197, 230, 286, 296, 297, 301, A-2, A-3
302, 313, 326, 328, 353 Ketonuria, 105, 197
Hypogonadism, 263 Ketosis, 123, 124, 167, 221, 233, 281-285
Hypogonadotropic hypogonadism, 263
Hypokalemia, 262 L
Hypoketotic hypoglycemia, 196, 351 Lactate dehydrogenase, 279, 325
Hypophosphatemia, 262 Lactic acid, 197, 279-282, 285, 297, 298, 300, 302,
Hypoproteinemia, 4 314, 315, 325, 326
Hyporeflexia, 281 Lactic acidemia, 280, 282, 296
Hypospadias, 197 Lactic acidosis, 279-281, 283, 301

Lactose, xiv, 262-264, 266, 267, 298, 299 3-Methylcrotonyl-CoA carboxylase, xii
LDL receptor, xvi 3-Methylcrotonyl-CoA carboxylase deficiency, 103, 105
Lecithin:cholesterol acyltransferase deficiency, xv 3-Methylcrotonylglycine, 111
Lethargy, 52, 65, 75, 103, 105, 174, 220, 221, 231, 3-Methylcrotonylglycinuria, xii, 105, 111, 113
314, 326, 351, 366, 406, 419 N-Methyl-∆-aspartate, 220
Leucine, x, xi, xii, xiii, 74-79, 81-83, 85, 103-115, 117, 5, 10-Methylenetetrahydrofolate reductase deficiency,
124-127, 129-131, 197, 198 138
Leucine catabolism, 103 Methylenetetrahydrofolate reductase, 139
Leukopenia, 104 3-Methylglutaconic acid, 111
Lipemia retinalis, 280, 338 3-Methylglutaconic aciduria, xii, 105, 108, 111
Lipoamide dehydrogenase deficiency, 281 3-Methylglutaconyl-CoA hydratase, xii
Lipoic acid, 74, 281 3-Methylglutaconyl-CoA hydratase deficiency, 103, 105
Lipoprotein lipase, 338 3-Methylglutaric acid, 111
Lipoprotein lipase deficiency, 338, 339 3-Methylhistidine, 411, 425
Lipoprotein lipase inhibitor, xv Methylmalonic acid, 230, 231, 233, 237
Liposyn II, 76, 77, 105, 106, 124, 125, 232 Methylmalonic acidemia, xi, xiii, 230, 231, 233, 236,
Liver failure, 49, 314 237, 240, 258
Liver parenchymal cells, 196 Methylmalonic aciduria, xi, 139
Liver transplantation, 231 Methylmalonyl-CoA, 138
Long-chain-CoA dehydrogenase, 350 Methylmalonyl-CoA mutase, 230, 231
Long-chain-acyl-CoA dehydrogenase deficiency, xv, Methylmalonyl-CoA mutase —, xiii, 230
351 Methylmalonyl-CoA mutase º, xiii, 230, 231
Long-chain-fatty acid oxidation defects, 351-353 N5-Methyltetrahydrofolate, 137
Long-chain-fatty acids, xv, 351 5-Methyltetrahydrofolate, 139
Long-chain-hydroxyacyl-CoA dehydrogenase 5-Methyltetrahydrofolate-homocysteine
deficiency, xv, 350, 352, 357 methyltransferase, 137-139
Long-chain-unsaturated fatty acids, xiii, xiv Metronidazole, 237
Low blood pH, 231 Microcephaly, 2, 33, 281
Lysine, xiii, 78, 125, 166-170, 172-175, 178, 197, 198, Microsomal 7-dehydrocholesterol reductase, xv
209, 210, 213, 214, 233, 326, 379, 384, 406 Microsomal phosphate transport, 297
Lysinuric protein intolerance, xiii, 209, 214, 215, 217, Mitochondrial acetoacetyl-CoA thiolase, 123, 124
406, 419 Mitochondrial acetoacetyl-CoA thiolase deficiency, 123
Mitochondrial fatty acid oxidation defects, 350, 351,
M 359-362
Macrocephaly, 166, 167 Mitochondrial ornithine transport protein, 406
Maillard reaction, viii, 6, 37, 53, 66, 80, 109, 127, 143, Mitochondrial transport defect, 406
171, 212, 235, 382, 409, 423 Mitochondrial trifunctional protein, 350
Malar flushing, 138 Mitochondrial trifunctional protein deficiency, 351
Maleylacetoacetate, 49 Motor delay, 279
Maleylacetoacetic acid isomerase, xii, 49, 50, 64 Multiple acyl-CoA dehydrogenase, xiii
Maple syrup odor, 75 Multiple acyl-CoA dehydrogenase deficiency, 196
Maple syrup urine disease, x, xi, xii, 74, 75, 84, 85, Muscle phosphorylase, xiv
100, 103, 104 Muscle weakness, 350, 351
Maternal phenylketonuria, 33, 46 Musty odor, 2
Medium-chain-acyl-CoA dehydrogenase, 350 Myocardium, 196
Medium-chain-acyl-CoA dehydrogenase deficiency, xv, Myoclonic jerks, 105
350, 351, 357 Myoclonic seizures, 166, 221, 279, 280
Medium-chain-fatty acid oxidation defects, 352, 353 Myoglobinuria, 351
Medium-chain-triglycerides, xv, 351-353, 355, 357-359
Melena, 123, 124 N
+
Mental aberrations, 2 NAD , 74, 196
Mental retardation, x, 2-4, 33, 63, 64, 105, 107, 137, Nasogastric feeding, 76, 77, 105, 106, 124, 125, 168,
138, 209, 264, 326, 419 174, 232, 237, 238
Metabolic acidosis, 63, 75, 78, 103-105, 108, 115, 123, Nausea, 285, 286, 314
124, 126, 166-168, 196-198, 230, 314, 326, 351 Neocalglucon, 267, 268
Methionine, xiii, xiv, xvi, 78, 107, 126, 137-142, 144- Neonatal hyperparathyroidism, 366, 367
149, 152, 161, 220, 230, 231-239, 243, 244, 247, NeoSure, A-7
314, 315, 339 Nephrocalcinosis, 367
Methionine-S-adenosyltransferase, xiii, 137 Nephropathy, 50
2-Methylbutyric acid, 197 Neurologic abnormalities, 2, 63, 64
2-Methylbutyrylglycine, 197 Neurologic crises, 51, 52, 167, 169
Methylcitrate, 231, 233 Neurologic damage, 220
Methylcobalamin, 137, 138 Neurologic deterioration, 2, 3, 166-168, 221, 264
Neurologic dysfunction, 75 Phenylacetylglutamine, 408, 422
Neurologic impairment, 75, 167, 170, 174, 231, 263 Phenylalanine, x-xii, 1-12, 33-40, 42, 49-58, 63-70, 78,
Neutropenia, 104, 231, 296, 297, 303 108, 126, 140, 233, 234
Niacin, 162, 170, 408, 409, 421-423 Phenylalanine hydroxylase, x, xii, 1-3, 34
Nicotinamide adenine dinucleotide, 196 Phenylalanine hydroxylase deficiency, 34
2 (2-Nitro-4-trifluoromethylbenzoyl)-1, 3-cyclo- Phenylketonuria, x-xii, 1-3, 8, 9, 11, 12, 29, 33, 41
hexanedione, 49-52 Phenyllactic acid, x
Nonketotic hyperglycinemia, xiii, 220, 221, 225, 227 Phenylpyruvic acid, x
Nonketotic hypoglycemia, 196 Phosphoenolpyruvate, 325
Normoglycemia, 281, 285, 298-300 Phosphoenolpyruvate carboxykinase, 325
Photophobia, 64
O Pigmentary retinopathy, 350, 351
Oculocutaneous lesions, 65 Pin-point pupils, 221
Odd-chain-fatty acids, xiii, xiv, 230, 231, 234, 240 Platelet dysfunction, 296
Offspring, 2, 33, 35, 196 Polycitra, 411, 422, 425
Opisthotonos, 75, 105 Polycose, xiv-xvi, 6, 11, 36, 53, 57, 66, 67, 69, 79, 83,
Organic acidemias, xi, 221 109, 127, 142, 143, 147, 168, 170, 171, 199,
Organic acids, 51, 55, 65, 68, 71, 75, 105, 107, 110, 200, 202, 232, 235, 236, 268, 283, 284, 287,
121, 124-126, 166, 168, 173, 197, 198, 201, 221, 299-301, 304, 318, 328, 330, 331, 340, 342, 343,
231, 237, 240, 355 354, 357, 358, 360, 369, 382, 383, 408, 412,
Organic acidurias, 196, 406, 419 422, 426, 427, A-9
Ornithine transcarbamylase, 418, 419 Polyunsaturated fatty acids, xvi, 231, 234
Ornithine transcarbamylase deficiency, xvi, 418-421, Poor appetite, 210, 220, 221
426 Poor feeding, 103, 104, 230, 313, 314, 406, 419
Ornithine transport defect, xvi Poor growth, 4, 5, 75, 78, 126, 141, 169, 211, 222,
Ornithine, xvi, 209-211, 213-215, 379-381, 383, 384, 233, 234, 314, 381, 408, 421
406-408, 411-413, 418 Poor suck, 75
Ornithine-∆-aminotransferase, xvi, 379-381, 406 Potential renal solute load, viii, 7, 9, 54, 56, 67, 80, 82,
Ornithinuria, 381 110, 112, 128, 130, 143, 145, 172, 175, 200,
Orotic acid, 210, 381, 406 202, 213, 223, 225, 236, 239, 266, 267, 285,
Orotic aciduria, 407, 418, 420 287, 301, 317, 329, 330, 341, 342, 355, 357,
Osmolarity, viii, 6, 7, 10, 11, 37, 39, 40, 53, 54, 56, 57, 358, 370, 372, 383, 385, 410, 412, 424, 426,
67, 69, 79, 80, 83, 84, 109, 110, 112-114, 127, 427, A-22
128, 130-132, 142, 143, 145-147, 170-172, 175, Pregnancy, 33-35, 39, 41, 196, 221, 350
199, 200, 202, 212, 213, 215, 222, 223, 225, Proline, 140, 234, 326, 406
232, 235, 236, 239, 240, 265-267, 283, 285, 287, Pro-Phree, xiii, xiv, xvi, 6, 11, 53, 57, 66, 67, 79, 109,
301, 317, 328-330, 341, 342, 354, 355, 357, 358, 127, 142, 143, 147, 168, 170, 171, 209, 212,
369, 370, 372, 382, 383, 385, 409, 410, 412, 213, 215, 216, 220, 222, 223, 225, 226, 235,
413, 422- 424, 426-428, A-20, A-21 236, 268, 317, 318, 382, 383, 385, 386, 387,
Osteopenia, 3, 4, 52, 65, 78, 106, 125, 126, 141, 169, 408, 422, A-3, A-10
233, 282, 381, 408, 421 Propimex, xiii, xiv, 230, 232, 234-237, 239, 240, 242,
Osteopetrosis, xvi, 366-368, 370, 371 A-2, A-3
Osteoporosis, 112, 138, 209, 211, 296 Propionic acid, 231, 233, 237, 240, 243
Ovarian failure, 264 Propionic acidemia, xiv, 230, 231, 234, 236, 240, 258
Oxaloacetate, 279, 325-327 Propionylcarnitine, 231, 233
Propionyl-CoA, 123, 138
P Propionyl-CoA carboxylase, xiv, 230, 231, 234
Palmo-plantar lesions, 65 Propionylglycine, 231
Pancreatic amylase, 298, 299, 304 Proteinuria, 314
Pancreatitis, 140, 231, 280, 296, 338, 339 ProViMin, xiii, xiv, xv, xvi, 106, 108, 114, 118, 199,
Pancytopenia, 104, 197, 231 200, 202, 203, 279, 283-285, 287, 289, 296, 299-
Pantothenic acid, xii, 108, 408, 409, 421-423 301, 304, 308, 325, 328-332, 338, 340-345, 353-
Parahydroxyphenyl, 51, 55, 65 355, 357-359, A-3
Parahydroxyphenylpyruvic acid dioxygenase, 50 Proximal myopathy, 197
Parathyroid hormone, 366 Psychomotor retardation, 50, 167, 280, 281, 366
Parathyroid hyperplasia, 366 Pyridoxal phosphate, 74, 138
Pathophysiologic changes in the brain, 231 Pyridoxine, xi, xiii, xvi, 138, 223, 379, 380-382, 408,
Pedialyte, 11, 57, 69, 147, 202, 268, 318, 331, 343, 409, 421, 423
358, A-9 Pyroglutamic acid, 425
Peripheral neuropathy, x, xiii, 138, 350, 351, 381 Pyrophosphate transport, 297
Phenex, xii, 1, 4-11, 27, 33, 36-40, 43, A-2, A-3 Pyruvate, 138, 279-282, 285, 325, 326
Phenylacetic acid, x, 408, 422 Pyruvate carboxylase, 279, 325-327
Pyruvate carboxylase apoenzyme, 325
Pyruvate carboxylase apoprotein, 325 Short-chain-hydroxyacyl-CoA dehydrogenase, 350
Pyruvate carboxylase deficiency, xv, 325, 326, 332-335 Short-chain-hydroxyacyl-CoA dehydrogenase
Pyruvate dehydrogenase complex, 279-281, 325 deficiency, xv, 351
Pyruvate dehydrogenase complex defect, xv, 279-282, Similac, vii, xiii, xiv, 9, 12, 56, 58, 70, 82, 87, 106, 112,
284, 288 117, 130, 133, 145, 148, 168, 175, 178, 213,
Pyruvate dehydrogenase kinase, 280, 283 215, 216, 225, 226, 239, 243, 316-318, 321, 330,
Pyruvate kinase, 325 332, 373, 385, 387, 412, 414, 426, 429, A-6
Pyruvic acid, 281 Similac Lactose Free, A-7
Skeletal abnormalities, 210
Q Skeletal changes, 138
Quinolinic acid, 166, 420 Skin desquamation, 78, 107, 126, 233
Smith-Lemli-Opitz syndrome, xv
R Sodium benzoate, 114, 211, 216, 220, 221, 224, 226,
Rachitic changes, 368 232, 407-409, 411, 414, 420, 421, 423, 425, 429
RCF, xiv, xv, xvi, 279, 283-285, 287, 289, 296, 299- Sodium bicarbonate, 126, 326
301, 304, 308, A-3 Sodium phenylacetate, 211, 216, 232, 408, 420-423,
Recommended Dietary Allowances, vii, xii-xvi, 4, 35, 425, 429
52, 65, 75, 78, 107, 126, 139, 141, 169, 170, Sodium phenylbutyrate, 211, 216, 407-409, 411, 414,
211, 222, 233, 265, 282, 298, 316, 408, 421, A- 420-423, 425, 429
16 Sodium propionate, 234
Recommended Dietary Intakes, vii, 6, 37, 45, 53, 54, Sorbitol, 313-318, 320
67, 80, 109, 110, 128, 143, 171, 200, 212, 223, Spasticity, 167, 406, 419
236, 265, 284, 301, 315-317, 329, 341, 355, 369, Speech delay, 279
383, 409, 421, 422, 423, A-14, A-15 Speech disabilities, 351
Redness of buccal mucosa, 78, 126, 233, 234 Splenomegaly, 338
Reduced bone mass, 280 Steatosis, 314
Remnant receptor defect, xvi Stem cell differentiation, 238
Renal abnormalities, 352 Strychnine, 220
Renal calculi, 280, 282 Stupor, x, 104, 419
Renal cysts, 167, 197 Suberic acid, 197
Renal failure, 231 Succinylacetone, x, 49-51, 55
Renal insufficiency, 296 Succinyl-CoA, 138
Renal proximal tubular dysfunction, 314 Sucrose, xiv, 298, 299, 306, 313-318, 320
Renal solute load, 7, 54, 67, 80, 110, 128, 143, 172, Sudden infant death syndrome, 351
200, 213, 223, 236, 266, 285, 301, 329, 341, Sulphite oxidase deficiency, xvi
355, 370, 383, 410, 424, A-22 Supravalvular aortic stenosis, xvi
Renal tubular disease, 210 Sweaty-feet odor, 103, 104, 197
Renal tubular dysfunction, 50, 314
Respiratory insufficiency, 221 T
Reye's syndrome, 105, 166, 197, 351, 406, 419 Tachypnea, 103, 104, 197
Rhabdomyolysis, 138, 351 Tetrahydrobiopterin, xi, xii
Riboflavin, xiii, 166, 167, 170, 171, 173-175, 196, 198- Tetrahydrobiopterin deficiency, 1
200, 351-354, 357, 363 Thiamin, xi, xii, xv, 74-76, 280-282, 284, 325-327
Rickets, 50 Thiamin pyrophosphate, xi, 74
Rocaltrol, 52 Threonine, xiii, xiv, 78, 107, 126, 140, 230-239, 243,
244, 247
S Thrombocytopenia, 104, 231, 314, 371
Salicylate toxicity, 123 Thymic hypoplasia, 209
Salicylate, 114, 123 Thyroxin-binding globulin, 210
Sarcosine, 197 Tiglic acid, 231
Sarcosinuria, 196 Tiglylglycine, 124
Sebacic acid, 197 Transient hyperammonemia, 406, 419
Seizures, 2, 63, 74, 75, 104, 105, 138, 167, 169, 209, Transport protein defect, 407
221, 279, 280, 281, 283, 284, 285, 313, 350, Transsulfuration pathway, 137
351, 406, 419 Transthyretin, viii, 4, 5, 8, 38, 52, 55, 65, 68, 78, 81,
Sepsis, 103, 262, 263, 366 111, 126, 129, 139, 141, 144, 169, 173, 201,
Serine, 78, 107, 126, 138, 140, 210, 233, 234, 420 211, 214, 222, 224, 233, 237, 282, 285, 302,
Serotonin, 104, 420 356, 381, 384, 408, 411, 421, 425
Shock, 313, 419 Trauma, viii, 11, 57, 69, 84, 108, 114, 115, 132, 147,
Short-chain-acyl-CoA dehydrogenase, 350 175, 202, 215, 225, 240, 267, 268, 317, 330,
Short-chain-acyl-CoA dehydrogenase deficiency, xv, 343, 358, 413, 428
351 Trembling, 314
Short-chain-fatty acid oxidation defects, 352, 353 Tremors, 78, 103, 126, 233
Triacylglycerols, 297, 298, 302, 338, 339, 341
Trimethylamines, 234
Tryptophan, xiii, 104, 162, 166-170, 172-175, 178,
194, 197, 198, 220, 420
Tryptophan hydroxylase, x, 1
Twitching, 406, 419
Tyramine, 63
p-Tyramine, 65, 68
Tyrex, xii, 49, 53-57, 59, 63, 66-69, A-2, A-3
Tyrosine, x-xii, 1-11, 34-36, 38-40, 49-58, 63-70, 78,
126, 127, 140, 233, 234, 314, 315, 420
Tyrosine aminotransferase, xii, 50, 63, 64, 65
Tyrosine hydroxylase, x, 1
Tyrosinemia, 50, 64
Tyrosinemia type I, 60
Tyrosinemia type Ia, x-xii, 49-51, 58
Tyrosinemia type Ib, xii, 49-51, 58
Tyrosinemia type II, xii, 50, 63, 64, 69-71
Tyrosinemia type III, xii, 50, 63, 64, 69-71
Tyrosinemia type IIIa, 63
Tyrosinemia type IIIb, 63
U
Ubiquinone, 196
Urate, 314, 315, 351
Urea cycle disorders, 418, 429, 430
Urea cycle enzyme defects, 406, 419
Urea cycle function, 209
Uric acid, 297, 302
Uridine diphosphate-galactose-4-epimerase, 262, 263
Uridine diphosphate-galactose-4-epimerase deficiency,
263
Uridine therapy, 263
V
Valine, x-xiv, 74, 76-79, 81-83, 85, 107, 124-127, 129-
131, 197, 198, 230-239, 243, 244, 247
Valproate, 172, 406, 419, 428
Very-long-chain-acyl-CoA dehydrogenase, 350
Very-long-chain-acyl-CoA dehydrogenase deficiency,
xv, 351
Very-long-chain-fatty acid oxidation defects, 352, 353
Vi-Daylin Multivitamin + Iron, A-10
Vitamin A, 37, 38, 139
Vitamin B12, xi, 8, 35, 37, 38, 138, 231
Vitamin B6, 138, 139, 379, 381
Vomiting, 49, 50, 75, 103-105, 166, 167, 197, 200,
210, 220, 221, 230, 231, 262, 263, 280, 285,
313, 314, 328, 350, 351, 353, 354, 406, 419
Von Gierke's disease, 296
W
Williams syndrome, xvi, 366, 367, 370

Book Whole Ross Nutrition Support Protocol

Diunggah oleh

Informasi Dokumen

Deskripsi Asli:

Judul Asli

Hak Cipta

Format Tersedia

Bagikan dokumen Ini

Bagikan atau Tanam Dokumen

Opsi Berbagi

Apakah menurut Anda dokumen ini bermanfaat?

Apakah konten ini tidak pantas?

Hak Cipta:

Format Tersedia

Book Whole Ross Nutrition Support Protocol

Diunggah oleh

Hak Cipta:

Format Tersedia

To order products in the Ross Metabolic Formula System, call:

8:30 AM - 5:00 PM EST, Monday - Friday, except holidays.

For answers to questions about nutrition management of patients with

Nutrition Support Protocols

Medical Director, Medical and Regulatory Affairs

Vice President, Medical and Regulatory Affairs

Ross Products Division

Library of Congress, Catalog Card No 97-066096

A6224/(500)/June, 2001 LITHO IN USA

Karen Amorde-Spalding, MS, RD Reuben Matalon, MD, PhD

Ross Products Division/Abbott Laboratories

© 2001 Ross Products Division iii

Practical Aspects of Nutrition Support of Inborn Errors of Metabolism........................................vii

DISORDERS OF AMINO ACID METABOLISM

Branched-chain amino Acids

Sulfur Amino Acids

Other Amino Acids

DISORDERS OF CARBOHYDRATE METABOLISM

iv © 2001 Ross Products Division

DISORDERS OF LIPID METABOLISM

© 2001 Ross Products Division v

INDEX ........................................................................................................................... I-1

vi © 2001 Ross Products Division

Measuring Medical Foods

Supplying Restricted Amino Acids

© 2001 Ross Products Division vii

Recognizing the Maillard Reaction

Monitoring Amino Acid Concentrations

Tuning the Prescription

viii © 2001 Ross Products Division

Changing Medical Foods

Masking the Taste of Free Amino Acids

Selecting Nutrient Analysis Computer Software

General Principles of Nutrition Support of Genetic Disease

© 2001 Ross Products Division ix

G ene A B Gene BC G ene C D

Enzym e A B Enzym e B C Enzym e C D

1. A deficiency of product D or some compound derived only from D. For example, in

5. Increased production of alternative product (eg, E, through little-used metabolic pathways.

6. Inhibition of alternative pathways by accumulated substrate (eg, C in CD impairment). For

x © 2001 Ross Products Division

3. Providing alternative metabolic pathways to decrease accumulated toxic precursors in

4. Supplying products of blocked primary pathways. As examples, arginine (ARG) is supplied in

© 2001 Ross Products Division xi

Inborn Error and Defect Nutrient(s) To Modify Vitamin-Responsive Ross Metabolic

RDAs for age. be supplemented

Inborn Error and Defect Nutrient(s) To Modify Vitamin-Responsive Ross Metabolic

Inborn Error and Defect Nutrient(s) To Modify Vitamin-Responsive Ross Metabolic

Inborn Error and Defect Nutrient(s) To Modify Vitamin-Responsive Ross Metabolic

Inborn Error and Defect Nutrient(s) To Modify Vitamin-Responsive Ross Metabolic

© 2001 Ross Products Division xvii

Nutrition Support of Infants, Children, and Adults With

Dihydrobiopterin Dihydropteridine reductase

Dietary protein H4 biopterin H2 biopterin

Orthohydroxy- Phenylpyruvate* Phenylethylamine

(N) = several steps

Indicates sites of possible enzyme defects

Figure A. Phenylalanine metabolism in phenylketonuria

© 2001 Ross Products Division Phenylketonuria 1

III. Outcome of Nutrition Support

IV. Establish Diagnosis

V. Rationale for Nutrition Support

Date of Birth: //__