Overview
What the Metabolic Defect Does
Phenylketonuria (PKU) is an autosomal recessive disorder in which phenylalanine cannot be handled normally.
Phenylketonuria (PKU) is an autosomal-recessive disorder in which phenylalanine cannot be handled normally. Usually, the liver enzyme phenylalanine hydroxylase converts phenylalanine to tyrosine. Tetrahydrobiopterin is required for that reaction, so a defect involving either the enzyme or its cofactor can produce PKU. The result is a metabolic bottleneck: phenylalanine enters the pathway, but the conversion route is impaired. Blood phenylalanine rises, and excess phenylalanine reaches the brain, where it interferes with neurotransmitter production, myelination, and normal brain development. Untreated or poorly controlled PKU can therefore cause permanent developmental impairment, seizures, and behavioural changes rather than merely a harmless abnormal laboratory value. PKU is treated from infancy because neurological injury can begin before obvious symptoms appear. The goal is not to remove all protein or all phenylalanine. Phenylalanine is an essential amino acid; the child needs a carefully measured amount for growth while avoiding excess.