phenylketonuria

phenylketonuria A genetic disease affecting the metabolism of phenylalanine. Phenylalanine is normally metabolized to tyrosine, catalysed by phenylalanine hydroxylase. Impairment of this reaction leads to a considerable accumulation of phenylalanine in plasma and tissues (up to 100 times the normal concentration) and metabolism to phenylpyruvate, phenyllactate, and phenylacetate, collectively known as phenylketones, which are excreted in the urine.

The very high plasma concentration of phenylalanine causes disruption of brain development, and if untreated there is severe mental retardation. All infants are screened for phenylketonuria shortly after birth (by measurement of plasma phenylalanine); treatment is by very strict limitation of phenylalanine intake, only providing sufficient to meet requirements for protein synthesis. Once brain development is complete (between the ages of 8 and 12 years) dietary restriction can be relaxed to a considerable extent, since high concentrations of phenylalanine seem to have little adverse effect on the developed brain. There may, however, be benefits from continuing dietary restriction into adult life, and phenylketonuric women require extremely careful dietary control through pregnancy to avoid damage to the fetus's developing brain.