AbstractThe hepatic phenylalanine hydroxylating system consists of three essential components, phenylalanine hydroxylase, dihydropteridine reductase and the non‐protein coenzyme, tetrahydrobiopterin. The reductase and the pterin coenzyme are also essential components of the tyrosine and tryptophan hydroxylating systems. Recent studies have shown that there are three distinct forms of phenylketonuria or hyperphenylalaninaemia, each caused by the lack of one of these essential components. The variant forms of the disease that are caused by the lack of dihydropteridine reductase or tetrahydrobiopterin are characterized by severe neurological deterioration, impaired functioning of tyrosine and tryptophan hydroxylases and the resultant deficiency of tyrosine‐ and tryptophan‐derived monoamine neurotransmitters in brain.