Clinical meaning
Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH), which normally converts the amino acid phenylalanine to tyrosine in the liver. Without this enzyme, phenylalanine accumulates in the blood and crosses into the brain, where it interferes with normal brain development by disrupting myelination, neurotransmitter synthesis, and protein formation. If untreated, PKU causes severe intellectual disability, seizures, behavioral problems, and a musty body odor (from phenylacetic acid in sweat and urine). PKU is detected through newborn screening (heel stick blood test performed 24-48 hours after birth). Early dietary restriction of phenylalanine prevents brain damage and allows normal intellectual development.