Synonyms

PKU,
phenylalanine hydroxylase,
PAH, phenylalanine,
Phenylpyruvic acid,
Phenylacetic acid,
Hyperphenylalaninemia type I,
Folling's disease,
Phenylpyruvic oligophrenia
Background
Phenylketonuria (PKU) is the most
common inborn error of amino acid
metabolism.

Deficiency of the enzyme
phenylalanine hydroxylase (PAH) :

accumulation of phenylalanine in the
plasma (>1200 mmol/L;

excretion of phenylpyruvic acid and
phenylacetic acid in the urine.

Phenylalanine has ketogenic and
gluconeogenic intermediates
Contribute to the glucose pool
Play a role in normal brain
development and function.
PKU is detected by screening
newborns.
Patients treated with a diet low in
phenylalanine can lead a normal
life.

Pathophysiology:
The classic type of PKU is caused by a deficiency of PAH, resulting
in increased levels of phenylalanine in body fluids.

PAH catalyzes the conversion of L-phenylalanine to L-tyrosine,

Other types of PKU include PKU caused by impaired synthesis of
BH4, GTP-CH I, 6-pyruvoyl tetrhydropterin (6-PTS), or
dihydropteridine reductase (DHPR).

Patients with the BH4 cofactor deficiency have more severe
neurologic problems that are not completely corrected by the dietary
reduction of phenylalanine.

The learning disabilities in patients with PKU who are adequately
treated may result from reduced production of neurotransmitters as
a result of deficient tyrosine transport across the neuronal cell
membranes.


Frequency
In the US: The incidence of classic PKU is
approximately 1 case per 15,000 births.

Internationally: 4 cases per 100,000 individuals
incidence is 350 cases per
million live births.

Approximately 0.04-1% of the residents in
mental retardation clinics are affected by PKU.

Mortality/Morbidity:
Patients with PKU who are not treated have
severe mental retardation.

Psychologic problems, agoraphobia
Race: PKU is common in whites and Asians and
is rare in blacks.

Sex: No sexual predilection exists for PKU.
Untreated maternal PKU increases the risk for
developmental problems in offspring.

Age: PKU can commonly be recognized in
newborns with the help of newborn-screening
programs.

CLINICAL FEATURE

History:
- Most patients appear healthy at birth.
- In adult patients who stop dietary treatment,
neurologic
dysfunction may occur.

Physical:
Skin
Fair skin and hair impairment of melanin
synthesis

Eczema (including atopic dermatitis)
Light sensitivity
Pyogenic infections keratosis pilaris
Decreased number of pigmented nevi
Sclerodermalike plaques



Other manifestations
-Mental retardation
-Musty odor
-Epilepsy (50%)
-Extrapyramidal manifestations,
such as parkinsonism
-Eye abnormalities, such as
hypopigmentation

CAUSES

PKU is an autosomal recessive
disorder caused by mutations
at the PAH locus on bands
12q22-24.1.

Other causes of PKU include
BH4 and DHPR deficiency.

DIFRENSIAL DIAGNOSIS
Hyperphenylalaninemia
Tetrahydrobiopterin deficiency
Tyrosinemia
Liver disease
Other diseases with mental retardation
Tyrosinemia type II (Richner-Hanhart
syndrome)
Childhood systemic sclerosis

WORKUP
Lab Studies:
screening (enzymatic determination of
phenylalanine, and the Guthrie test as a
bacterial inhibition assay)
Perform screening on blood samples
during the first week of life.

Imaging Studies:
Perform cranial MRI in adults who have
neurologic dysfunction;
the most severely affected brain structures
regarding volume loss are the cerebrum,
corpus callosum, hippocampus, and pons.

Perform cranial magnetic resonance (MR)
spectroscopy to determine brain
metabolite concentrations and brain
compartmentation.

TREATMENT
Medical Care:
Treatment a diet low in phenylalanine
tyrosine supplementation is required
for normal psychomotor development.


BH4 supplementation (5-20 mg/kg) has been
applied in PKU treatment,

Consultations:
Consult a psychologist for assessment and
management of mental disorders.
Consult a nutritionist for dietary instructions.

Diet
Instruct patients to do the following:
Selectively restrict phenylalanine consumption (ie,
approximately 250-550 mg/d or 40-60 mg/kg/d in newborns).
Supplement the diet with tyrosine.
Avoid the use of products containing aspartame (artificial
sweetener).
Aspartame is used widely in medicines, vitamins, beverages,
and many other products.
Eliminate all high-protein foods (eg, meat and meat products,
milk and dairy products, nuts, legumes), and introduce low-
protein foods (eg, fruits, vegetables, breads).
Activity: Advise continuation of normal activity in patients
who are adequately treated.

Complications:

Agoraphobia is a complication.

Prognosis:

The prognosis for normal intelligence is good when
patients have been put on a diet low in phenylalanine in
the first month of life.

Patient Education:

Teach patients how to initiate and continue the diet.
Educate women with PKU about the risks of untreated
pregnancy and the benefits of dietary treatment.