A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype

A European multicenter study of phenylalanine hydroxylase deficiency has led to a general system for prediction of metabolic phenotype based on genotype and to classification of 105 mutations. Mild hyperphenylalaninemia (MHP) and phenylketonuria (PKU) are allelic disorders caused by mutations in the gene coding for phenylalanine hydroxylase (PAH). Both mutations were found in 686 patients in seven locations in Europe. Based on the phenotypic characteristics of 297 functionally hemizygous patients, 105 of the mutations were assigned to one of four arbitrary phenotype categories. Data show that the PAH-mutation genotype is the primary determinant of metabolic phenotype in most PAH-deficiency patients. The disorder is autosomal recessive.