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 1 of the 8 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 2 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 the breath, skin, and urine if the condition has not been treated immediately from birth or if foods containing phenylalanine are consumed.

• Skin rashes (eczema)
• Microcephaly
• Tremors
• Jerking movements of the arms or legs (spasticity)
• Unusual hand posturing
• Seizures
• Hyperactivity
• Delayed mental and social skills
• Mental retardation
• A distinctive "mousy" odor to the urine and sweat
• Light coloration (frequent finding of light complexion, blond hair, and blue eyes)

• Enzyme assay to detect the carrier state (parents)
• Chorionic villus sample to detect fetal PKU (prenatal diagnosis)
• PKU screening (a heelstick blood sample from the infant to screen for PKU, mandatory in most states)

Genetic counseling is recommended for prospective parents with a family history of PKU. The carrier state for PKU can be detected by enzyme assays, and PKU can be diagnosed prenatally.

It is imperative that a woman with PKU who becomes pregnant adheres closely to the special low-phenylalanine diet, since accumulation of phenylalanine will damage the unborn baby even if the baby has not inherited the abnormality.