Phenylketonuria and other hyperphenylalaninemias.

Phenylketonuria (PKU) is an inherited error of metabolism. Its prevalence is estimated at 1/50.000 but ranges from 1/2600 in Turkey, 1/50.000 in the UK and 1/100.000 in Japan. In 98% of the cases, it is caused by the autosomal recessive transmission of a mutation of the PAH gene (12q23.2) which codes for phenylalanine hydroxylase (PAH), the enzyme that converts phenylalanine to tyrosine. In all other cases, it is caused by the autosomal recessive transmission of a mutation of one of the genes responsible for the synthesis or regeneration of tetrahydrobiopterin (BH4).These are: the GCH1 gene coding for GTP cyclohydroxylase1 (14q22.2), the PTS gene coding for 6-pyruvoyl-tetrahydropterine synthase (11q23.1), the PCBD gene coding for pterin-4α-carbinolamine dehydratase (10q22.2) or the QDPR gene coding for dihydropterin reductase (4p15.32). Most of these cases are caused by a dihydropterin reductase deficiency. They are called BH4 deficiency or defects in pterin metabolism. BH4 is a cosubstrate of phenylalanine hydroxylase (see figure at the end of the text) but it is also involved in the synthesis of the amino acids tyrosine, tryptophan and arginine. A deficiency in the production of these amino acids results in a deficiency of the neurotransmitters dopamine, serotonin and nitric oxide. In addition, in rare cases, hyperphenylalaninaemia may be caused by a mutation in DNAJC12, a protein responsible for the proper folding of PHA (4). [ABSTRACT FROM AUTHOR]