Phenylketonuria and Hyperphenylalaninemia

Abstract

Untreated phenylketonuria (PKU) causes intellectual deterioration, seizures, various neuropsychiatric symptoms, defects in pigmentation, eczema, and a characteristic “musty” odor. Today, most neonates are screened for hyperphenylalaninemia, which includes PKU. The incidence of PKU is on average one in 10 000 births. A low-phenylalanine diet introduced within the first weeks of life prevents the symptoms of this disease provided the treatment is well controlled and blood phenylalanine does not exceed normal levels too frequently during the first 8 years of life. Discontinuation of the diet at the age of 15 years may be feasible for some, but an increasing number of treatment centers recommend a relaxed dietary regime in patients with classical PKU. PKU is caused by a monogenic autosomal recessive defect of hepatic phenylalanine hydroxylase, which catalyzes the irreversible conversion of phenylalanine to tyrosine. The defect causes accumulation of phenylalanine and its metabolites, e. g., phenylpyruvate, leading to phenylketonuria and phenylacetate responsible for a “musty” odor in untreated patients. Different mutations in the gene coding for phenylalanine hydroxylase correlate with different phenotypes of the disease, i. e., classical PKU, milder forms of PKU, and benign persistent hyperphenylalaninemia.