Phenylketonuria

Key Features

• Mental retardation, hyperactivity, seizures, light complexion, and eczema characterize untreated patients

• Newborn screening for elevated plasma phenylalanine identifies most infants

• Disorders of cofactor metabolism also produce elevated plasma phenylalanine level

• Early diagnosis and treatment with phenylalanine-restricted diet prevents mental retardation

• an autosomal recessive trait, with an incidence in whites of approximately 1:10,000 live births

Clinical Findings

• There is little or no phenylalanine hydroxylase activity

• Patients with untreated phenylketonuria exhibit severe mental retardation, hyperactivity, seizures, a light complexion, and eczema

Diagnosis

• Infants should be screened during the first few days

• A second test is necessary when newborn screening is done before 24 hours of age, and should be completed by the third week of life

• Plasma phenylalanine and phenylalanine/tyrosine ratio are elevated in a child on a normal diet

• Plasma phenylalanine levels are persistently elevated above 1200 μM (20 mg/dL) on a regular diet, with normal or low plasma levels of tyrosine, and normal pterins

Treatment

• Dietary restriction of phenylalanine

• Phenylalanine levels should be maintained at less than 360 μM (6 mg/dL)