Phenylketonuria (PKU) is an inherited disorder of
amino acid metabolism caused by deficiency of the
enzyme phenylalanine hydroxylase (PAH). Historically PKU was a common genetic cause of severe learning difficulties and developmental delay, but with the introduction of newborn screening and early dietary management, it has become a treatable disease and people born with PKU should now have IQs and achievements similar to their peers. Dietary treatment, however, involves lifestyle changes that pervade most aspects of daily life for an individual and their family. A simple pharmacological treatment for PKU would have a great appeal.
Sapropterin hydrochloride is a synthetic form of
tetrahydrobiopterin, the cofactor for PAH. A proportion of mutant PAH
enzymes show enhanced activity in the presence of pharmacological doses of
sapropterin and, for some patients with milder forms of PKU,
sapropterin can effectively lower plasma
phenylalanine levels. This article discusses the potential place for
sapropterin in the management of PKU and how this expensive orphan drug is being integrated into patient care in different healthcare systems.