Phenylketonuria occurs due to a defective enzyme phenylalanine hydroxylase. Classic PKU is present when plasma phenylalanine levels accumulate and exceed 20 mg/dL (1200 mmol/L). Urinary phenylalanine metabolites are raised.

Phenylalanine accumulation causes severe low IQ, microcephaly, epilepsy, depigmentation of the iris and hair. Guthrie bacterial inhibition test is used for infant testing. Fe chloride turns green in urine due to ketones.