Metabolic/Inherited Disorders

I. Definition
Metabolic disorders or inborn errors of metabolism are hereditary autosomal recessive traits and are caused
by the absence or reduced enzyme or cofactor activity

II. Management
A. Newborn screening
-most inherited metabolic disorders are associated with severe clinical illness that appears soon after birth
Blood test taken from a baby on the third day of life to identify those that are born with metabolic/inherited
problems. An early identification is important to avoid irreversible mental retardation or death. In most
developed countries (i.e., USA, Japan, Australia), newborn screening is offered as a routine public health
measure. In the Philippines, it is now available in some hospitals

B. Newborn screening tests for six metabolic/inherited disorders
1. Congenital hypothyroidism
2. Phenylketonuria
3. Congenital adrenal dyperplasia
4. Galactosemia
5. Homocystonuria
6. Maple syrup urine disease

C. Methods of Nutritional Management
1. Restriction of substrate
2. Supplementation of product
3. Supplementation of enzyme or cofactor
4. Combination of any or all of the methods

III. Nutritional Care
To maintain biochemical equilibrium for the affected pathway, provide adequate nutrients to support normal
growth and development, and support social and emotional development

IV. Assessment of Treatment
A. Regular monitoring of weight and growth pattern
B. Regular monitoring and evaluation of food diary
C. Careful and frequent monitoring of pertinent laboratory tests
D. Diet modifications are adjusted according to the above-mentioned factors
E. Continuous nutrition education to the family

V. Summary of some metabolic/inherited problems
Disorder Defective Enzyme Characteristics Diet
Amino Acids
1. Maple syrup urine
disease




2. Phenylketonuria




-keto-decarboxylase





Phenylalanine
hydroxylase



Increased blood concentration
of BCAA leucine, isoleucine,
and valine
Progressive severe MR,
prevented by early treatment

Increased blood concentration
of phenylalanine; increased
urine level of phenylpyruvic
acid and phenylacetic acid; MR

BCAA-free fomula (MSUD
powder, analog MSUD)




Low phenylalanine diet
Low phenylalanine
(Lofenalac) or phemylfree
formula (Phenyl Free,
Disorder Defective Enzyme Characteristics Diet




3. Homocystinuria





4. Tyrosinosis




Cystathionine
synthase




p-hydroxy-
phenylpyruvic acid




Increased methionine,
increased homocystine; arterial
& venous thrombosis, bony
abnormalities, dislocated lens,
mild to moderate MR
Maxamaid, Analog, X-Phen,
PKU-1, PKU-2); avoid
aspartame

Low protein; low methionine
diet with added L-cystine




Low phenylalanine and
tyrosine

Urea Cycle Disorders
1. Carbamyl
phosphate
synthetase defect

2. Ornithine trans-
carbamylase
deficiency


3. Citrullinemia





4. Arginosuccinic
aciduria

Carbamyl phosphate
synthetase


Ornithine
transcarbamylase (X-
linked)


Arginosuccinic acid
synthetase




Argino-succinidase

Increased plasma ammonia,
glutamine; vomiting, seizures,
coma, death, MR

Increased plasma ammonia,
glutamine, glutamic acid,
alanine; vomiting, seizures,
coma, death

Increased plasma citrulline,
ammonia, alanine; vomiting,
seizures, coma, death,
progressive developmental
delay

Increased plasma
arginosuccininc acid, citrulline,
ammonia, hypotonia, seizures,
vomiting, FTT, progressive
developmental delay

Low protein, keto-acid
mixture, sodium benzoate;
hemo- or peritoneal dialysis

Low protein and sodium
benzoate



Low protein, arginine,
supplements, sodium
benzoate



Low protein, arginine
supplement, sodium
benzoate; dialysis
Organic Acidemias
1. Methylmalonic
aciduria (acidemia)





2. Propionic acidemia

Methylmalonyl CoA or
coenzyme B12





Propionyl CoA
carboxylase

Increased organic acids,
ammonia, metabolic acidosis,
vomiting, seizures, coma, often
death, progressive,
developmental delays in
survival

Increased ammonia, propionic
acid in blood, metabolic
acidosis, increased methylcitric
acid in urine

Low isoleucine, threonine,
valine and methionine;
vitamin B12 1 mg/day IM




High kilocalories, low
protein, IV fluid, bicarbonate
Carbohydrates
1. Galactosemia




Galactose I-phosphate
uridyl transferase



Increased urine and blood
galactose; vomiting,
hepatomegaly, hypoglycaemia,
FTT, cataracts, MR, early

Galactose & lactose-free;
special formulas may be
used for infant feeding

Disorder Defective Enzyme Characteristics Diet


2. Hereditary
galactokinase


3. Fructose 1,6-
diphosphate
deficiency


Galactokinase



Fructose 1,6-
diphosphatase
sepsis

Increased blood, urine
galactose after feeding with
lactose, cataracts

Hypoglycemia, hepatomegaly,
hypotonia, metabolic acidosis,
on fructose introduction


Galactose and lactose-free



Fructose-, sucrose- and
sorbitol-free
Glycogen Diseases
1. Type O-glycogen
synthetase
deficiency

2. Type I: glucose 6-P
defect (Van Creveld-
Von Gierkes
Disease)

3. Type IIB: -1,4-
glucosidase defect
(acid maltase
deficiency)

4. Type III:
debranching
enzyme defect (limit
detrinosis or Forbes
disease)





5. Type IV: reduced
hepatic
phosphorylase
activity

6. Type V: branching
enzyme defect
(Hers disease)

Absence of glycogen
synthetase


Glucose-6-
phosphatase



-1,4-glucosidase




Amylo-1,6-glucosidase
defect








Hepatic
phosphorylase



-1,4 glycan 6-
glycosyl transferase

Liver has very low glycogen
content


Hypoglycemia, hyperlipidemia,
hepatomegaly, growth
retardation, osteoporosis,
metabolic acidosis

Muscle weakness, hypotonia




Hepatomegaly, growth failure,
hyperlipidemia, fasting
hypoglycaemia







Heptaomegaly, mild to
moderate, growth failure,
hyperlipidemia, fasting
hypoglycaemia

Hepatic deterioration, FTT,
cirrhosis, portal hypertension,
ascites, esophageal varices

High protein, frequent
carbohydrate feeding, extra
meal at night

Frequent feeding with raw
corn starch, high
carbohydrate, limited in
lactose & fructose, low fat

High protein




High protein, limited sugar
free sugar, frequent
feedings; total kilocaloric
distribution:
25-25% protein
40-50% CHO
25-35% fat
Nocturnal tube feedings of
corn starch

Nocturnal corn starch or
high carbohydrate
continuous enteral tube
feeding

Nocturnal tube feeding or
oral corn starch feedings


VI. Other inherited/congenital problems
Disorder Characteristics Treatment
Congenital hypothyroidism *low or absent thyroid hormone
*occurs in one of every 4,000 newborns
*part or all of the thyroid gland failed to develop
*enzyme needed to produce thyroid hormone is
missing
Thyroid hormone pills
Disorder Characteristics Treatment
Congenital adrenal
hyperplasia
*occurs in one of every 12,000 births
*salt is lost in the urine
*high levels of male hormones in both boys and
girls
Early detection to avoid serious illness
due to salt loss
Downs Syndrome
(Trisomy 21)
*associated with growth and mental retardation
*poor suck and swallow during infancy, drooling
*poor lip and tongue control
*hypotonia
*excessive weight gain/obesity
*dental problems: delayed tooth development,
periodontal disease, malocclusion, bruxism
*compromised cardiac status
Feeding evaluation by qualified
professional to develop appropriate
feeding program
Tube feeding if needed
Adjust texture of diet
Use adaptive feeding technique; good
dental hygiene
High kcal diet if weight gain is poor
Monitor Na intake if cardiac status is
compromised