[Phenylketonuria and hyperphenylalaninemia: clinico-genetic classification of 14 forms]

The current classifications of the clinical patterns of phenylketonurias and hyperphenylalaninemias are reviewed. On the basis of the literature data, a new classification considering the type of the mutant gene, the severity of the biochemical defect and the disease clinical course is proposed. All 14 hereditary determined patterns are divided into three groups: 1) with complete or partial deficiency of the major enzymes of the reaction of oxidation of phenylalanine into tyrosine; 2) with defects of enzymes in the chain of the cofactor synthesis; 3) with enzymatic defects in conjugated links of phenylalanine and tyrosine metabolism. Some forms are presented in the literature only as rare case reports and the underlying molecular disorders of some of them still remain to be explained. The genetic heterogeneity of phenylketonurias seems to-be much wider than is generally accepted and, therefore, the presented classification can not be considered as final.