Phenylketonuria Symptoms and Treatment

Phenylketonuria is an autosomal recessive disorder of amino acid metabolism. It is a rare disease with a frequency of approximately 1 in 10,000.

What is the pathology of phenylketonuria?

The main defect lies in impairment of conversion of amino acid phenylalanine to tyrosine and as a result there is an increased concentration of phenylalanine and its by-products in body fluids. The activity of main enzyme that metabolizes phenylalanine, i.e. phenylalanine hydroxylase is reduced. The accumulation excess phenylalanine in body fluids also cause disturbance of metabolism of other amino acids for synthesis of protein and neurotransmitters (some amino acids acts as neurotransmitter, e.g. glycine, glutamic acid, alpha-aminobutyric acid etc.). There is also reduced synthesis of norepinephrine and serotonin.

What are the symptoms of phenylketonuria?

Untreated cases of phenylketonuria are characterized by severe mental retardation and affected infants fail to attain normal developmental milestones. The affected infants are normal at birth but later on develop microcephaly and progressive impairment of brain functions. Seizures, hyperactivity etc. are also important symptoms. Skin may have characteristic “mousy odor” and hypo-pigmentation (because phenylalanine is competitive inhibitor of tyrosinase, a key enzyme synthesis of melanin, the pigment which gives color to skin and hairs) of skin and hairs. If diagnosed at birth and treated adequately, the affected babies do not show any of the above mentioned symptoms.

Treatment of phenylketonuria:

To prevent the symptoms of phenylketonuria from developing, especially mental retardation, the treatment should be started by 3 weeks of age. In developed countries all the babies are screened for blood phenylalanine level.

Treatment is based on dietary restriction of phenylalanine when blood phenylalanine level is more than 4 mg/100 ml. Special diets are available for management of phenylketonuria, which provide very low phenylalanine and provide supplementation of tyrosine (because in deficiency of phenylalanine hydroxylase, tyrosine can not be synthesized and it becomes an essential amino acid).

The aim of the therapy is to maintain blood phenylalanine level between 2 to 6 mg per 100 ml and dietary restriction of phenylalanine need to maintain indefinitely. Some mild cases of phenylketonuria may show increased tolerance to dietary phenylalanine if treated with tetrahydrobiopterin (5 to 20 mg/kg per day), which is an essential cofactor/coenzyme of phenylalanine hydroxylase.

Special note about phenylketonuria and pregnancy:

Treatment of phenylketonuria with dietary restriction has been almost 2 decades and many women treated may become pregnant or already become pregnant. It is of vital importance to control blood phenylalanine level before (at least 2 months prior to conception) and during pregnancy to prevent congenital defects and microcephaly (maternal phenylketonuria).

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