Phenylketonuria (PKU) is a human genetic disorder that occurs in about 1 in 15,000 births, but the incidence varies widely in different human populations from 1 in 4,500 births among the Irish to fewer than one in 100,000 births among the population of Finland.
PKU usually is caused by a defective gene for the enzyme phenylalanine hydroxylase (PAH). It is inherited as an autosomal recessive trait. A rarer form of the disease occurs when PAH is normal but its cofactor tetrahydrobiopterin (BH4) is not synthesised by the patient.
This enzyme normally converts the amino acid phenylalanine to tyrosine. If, due to a faulty or missing enzyme, this reaction does not take place, levels of phenylalanine in the body can be far higher than normal, and levels of tyrosine lower than normal. Excess phenylalanine in the blood harms brain development in the child, leading to mental retardation; low levels of tyrosine leads to lowered production of the pigment melanin, so children with this condition tend to be fair haired and blue eyed. The excess phenylalanine is converted instead into phenylketones, which are excreted in the urine - hence the name for this condition. The sweat and urine of an affected child has a musty odour due to these ketones.
The problem is readily detectable within days of birth from a small blood sample -- the Guthrie heel prick test, so screening for phenylketonuria is done routinely in most industrialised countries, usually combined with testing thyroid function and other genetic disorders of metabolism. If the condition is diagnosed early enough, an affected child can grow up with normal brain development, by eating a special diet low in phenylalanine. In those patients with a deficit in BH4 production, treatment consists of giving this cofactor as a supplement.