Phenylalanine hydroxylase (PAH) is a key enzyme in the catabolism of phenylalanine, and mutations in this enzyme cause phenylketonuria (PKU), a genetic disorder that leads to brain damage and mental retardation if untreated.
Rare mutations in PAH are causal to phenylketonuria (PKU), an autosomal recessive disease characterized by neuropsychiatric symptoms including intellectual disability.
Classic phenylketonuria is caused by a complete or near-complete deficiency of phenylalanine hydroxylase activity and without dietary restriction of phenylalanine most children will develop profound and irreversible intellectual disability.
The history of PKU is one of science in the discovery of an inborn error of metabolism and a chemical cause of mental retardation; and also one of technology with the development of methods to prevent disease.
The dysgenic effect (increase in prevalence of the PKU gene) from this reproduction will have negligible influence on the frequency of mental retardation from PKU over the next few centuries.