Phenylketonuria is a hereditary
metabolic disease, characterized by deficiency of
phenylalanine hydroxylase, an
enzyme necessary for the transformation of
phenylalanine into
tyrosine. Untreated,
phenylketonuria leads to
mental retardation, sometimes profound, as well as
hypopigmentation. Dietary
phenylalanine restriction allows patients to lead almost normal lives.
Phenylalanine is toxic to fetal development and severe disorders occur in the children of women whose
phenylketonuria is untreated during pregnancy. These women must be informed that they must plan pregnancy and begin
dietary restrictions in the preconceptional period. France has set up routine neonatal screening in view of the incidence of this disease (1/17000 in France) and the existence of effective treatment. Since 1970, approximately 1600 infants with
phenylketonuria have thus been diagnosed and treated. Strict metabolic control is necessary during the first 10 years of life, after which the diet can be progressively enlarged.
Dietary restriction must resume before any pregnancy. Advances in treatment: a study published in 2002 showed that some patients deficient in
phenylalanine hydroxylase are sensitive to pharmacological doses of
tetrahydrobiopterin (BH4), a cofactor of this '
enzyme essential to the transformation of
phenylalanine into
tyrosine. Some patients treated by this cofactor have normal levels of
phenylalanine intake. While only a few patients have so far received this alternative treatment, intermediate and long-term experiments are currently being evaluated.