What is the definition of classic phenylketonuria (PKU)?

• A. Deficiency of phenylalanine hydroxylase which prevents the hydroxylation of phenylalanine to tyrosine, causing a buildup of phenylalanine and a deficiency of tyrosine
• B. Deficiency of tyrosine
• C. Excess phenylalanine hydroxylase
• D. Normal phenylalanine metabolism

Answer: (A)

Classic phenylketonuria is defined by a deficiency of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine. When this step is blocked, phenylalanine accumulates in the blood and tissues while tyrosine production falls, making tyrosine an essential amino acid for these individuals. This metabolic block underpins the neurodevelopmental issues seen if the condition isn’t detected and treated early, which is why a lifelong low-phenylalanine diet with tyrosine supplementation is the cornerstone of management. The other options don’t fit: lacking tyrosine wouldn’t cause phenylalanine to pile up; having too much phenylalanine hydroxylase would enhance conversion rather than cause buildup; normal metabolism implies no PKU.