[Molecular basis for the heterogeneity of phenylketonuria]

The heterogeneity of phenylketonuria can be explained on the molecular basis. Because the phenylalanine-hydroxylating system consists of more than one enzyme, each enzyme can be mutated. Different mutations of the phenylalanine hydroxylase molecule resulting in a lack or reduction of enzyme activity can be anticipated. Enzyme activity lower than 1% compared to normals is correlated to the severe form; enzyme activity higher than 5% is correlated to the mild form of the disease. Phenylketonuria can also be caused by a defective synthesis or defective reduction of the cofactor. Patients suffer severe neurological symptoms, because of an impaired synthesis of dopamine and serotonin.