Phenylketonuria (PKU) is inherited as an autosomal recessive trait (both parents must pass on the defective gene for the child to be affected). The genetically determined abnormality in phenylketonuria is a missing enzyme called phenylalanine hydroxylase.

Phenylalanine is one of the eight essential amino acids found in protein-containing foods. In PKU, phenylalanine cannot be used in a normal fashion because of the missing enzyme. Subsequently, high levels of phenylalanine and two closely related phenylalanine derivatives build up in the body. These compounds are toxic to the central nervous system and cause brain damage.

Damage to the brain causes marked mental retardation by the end of the first year of life if the offending proteins are not scrupulously avoided. Older children may develop movement disorders (athetosis), rocking and hyperactivity.

PKU is a treatable disease that can be easily detected by a simple blood test. Most states require a screening test for all newborns, generally done with a heelstick shortly after birth.

Because phenylalanine is involved indirectly in the production of melanin, the pigment responsible for skin and hair color, children with phenylketonuria often have lighter complexions than their unaffected siblings. There is a characteristic "mousy" odor that results from the accumulation of phenylacetic acid. This odor may be detected on their breath, skin, and urine if the condition has not been treated immediately from birth or if foods containing phenylalanine are consumed.