Phenylketonuria

Inborn error of phenylalanine metabolism. Results in severe irreversible mental retardation at infancy.

1:10,000 to 12,000 live births in North America; considerable geographic variability.

Autosomal recessive.

Deficiency of the liver enzyme phenylalanine hydroxylase, which converts phenylalanine to tyrosine; it leads to accumulation of phenylalanine and abnormal metabolites thereof.

Neonatal screening programs for phenylketonuria (PKU) are established in many countries (Guthrie test). Elevated plasma levels of phenylalanine are seen in affected infants after protein feeding.

Affected infants are normal at birth. Untreated children develop severe mental retardation with movement disorders. They typically have pale, dry skin and blue eyes. Severe vomiting, mimicking infantile pyloric stenosis, may be the presenting feature. Typical mousy pungent odor caused by the excretion of phenylacetic acid. Perirectal eczema-like or scleroderma-like skin rash. Treatment consists of a diet low in phenylalanine.

Ensure patient is receiving appropriate diet.

There should be no difficulties with anesthetic management of children who are receiving appropriate dietary manipulation.

There are no specific implications.

Tetrahydrobiopterin (BH4) Deficiency: Of children with phenylketonuria, 1 to 2% have a defect in the gene coding for that cofactor of phenylalanine hydroxylase instead of a deficiency in the enzyme itself. BH4 deficiency also causes decreased synthesis of l-dopa, 5 hydroxytryptophan, and nitric oxide (NO). Without treatment, the most severe form leads to microcephaly, developmental delay, and progressive neurological deterioration with parkinsonian symptoms. Treatment includes the daily administration of l-dopa (up to 10 to 12 mg/kg/d) and 5-hydroxytryptophan (up to 8-10 mg/kg/d).