General description

Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutations in the PAH gene located on chromosome 12 (12q23.2). PKU follows an autosomal recessive inheritance pattern, meaning both copies of the gene must be mutated for the condition to manifest. The PAH gene encodes for phenylalanine hydroxylase, an enzyme essential for converting phenylalanine (Phe), an essential amino acid, into tyrosine (Tyr). This enzyme enables the breakdown of phenylalanine, but when its function is impaired or absent, phenylalanine accumulates in the blood, leading to elevated blood levels of Phe and an increase in phenylpyruvic acid, a metabolic byproduct, in the urine. This accumulation disrupts normal metabolic processes and can cause neurological symptoms, especially in newborns and infants.

If left untreated, PKU can lead to significant developmental delays in early childhood, typically beginning within the first few months to two years of life. Common symptoms include microcephaly, epilepsy, severe intellectual disability, and behavioral issues. Physical characteristics may include a musty or "mouse-like" odor, light skin, red hair, and eczema. In adults, excess phenylalanine and its metabolites can contribute to oxidative stress and may cause various mental health symptoms.