Phenylketonuria and its variants.

The hepatic phenylalanine hydroxylase system is complex, consisting of at least two enzymes and two non-protein cofactors. In classical phenylketonuria (PKU) the affect component has been shown to be the enzyme, phenylalanine hydroxylase. Recently, several variant forms of PKU have been identified which are due to deficiencies of two of the other components of the hydroxylase system, dihydropteridine reductase and tetrahydrobiopterin. In these cases, the defects lead to symptoms which are more severe than in PKU. Furthermore, since these two components are also required in the biosynthesis of the neurotransmitters, serotonin, dopamine and norepinephrine, treatment with a phenylalanine-restricted diet is not effective. Thus, it is important to distinguish PKU from one of its variant forms at as early an age as possible to institute alternate therapies. The methods for determining the affected component will be discussed.