A 5-year-old boy with severe mental retardation is brought to the physician because of a 4-week history of progressively frequent generalized tonic-clonic seizures. There is no available record of newborn screening. He has blond hair and blue eyes. Physical examination shows patches of itchy, dry, thickened skin on the face, neck, and inner creases of the elbows and knees. Serum studies for amino acid concentrations are pending. Urine studies show increased concentrations of phenylpyruvic and phenyllactic acids. The activity of which of the following enzymes is most likely defective in this patient?

Question

Quizplus · Accepted Answer

The symptoms and urine findings suggest phenylketonuria (PKU), which is caused by a deficiency in phenylalanine hydroxylase, leading to the accumulation of phenylalanine and its metabolites.  Missing or deficient phenylalanine hydroxylase results in hyperphenylalaninemia. The most widely recognized hyperphenylalaninemia (and most severe) is phenylketonuria (PKU). Untreated PKU leads to severe mental retardation. The mental retardation is caused by the accumulation of phenylalanine, which becomes a major donor of amino groups in aminotransferase activity and depletes neural tissue of a-ketoglutarate. The product of phenylalanine transamination, phenylpyruvic acid, is reduced to phenylacetate and phenyllactate, and all 3 compounds appear in the urine.

A 5-Year-Old Boy with Severe Mental Retardation Is Brought to the Physician