Phenylketonuria (PKU) is a genetic metabolic disorder characterized by complete or near-complete deficiency of an important enzyme known as phenylalanine hydroxylase (PAH). PAH is required for the proper metabolism of amino acid phenylalanine and it is responsible for processing dietary phenylalanine and converting it into neurotransmitters, hormones and other substance required by the body. In individuals affected by PKU, PAH deficiency can lead to a build-up of amino acid phenylalanine in the body and affect their neurological development. Depending on the level of PAH deficiency, PKU can be further classified as classic PKU and mild hyperphenylalaninemia.
Classic PKU is the more severe form and those affected, develop irreversible intellectual disability. Infants with classic PKU appear normal for the first few months. Initial symptoms displayed involve loss of interest in the surroundings, irritability, and behavioural problems. Later complications of untreated PKU include, seizures, microcephaly, behavioural problems, and developmental delay. As phenylalanine is involved in the production of the pigment melanin, patients with PKU tend to have lighter skin, hair, and eyes than their siblings. Affected individuals may also have musty body odour due to excess phenylalanine in the body.
Phenylketonuria is caused by mutations in the phenylalanine hydroxylase (PAH) gene.