Sapropterin dihydrochloride for phenylketonuria and tetrahydrobiopterin deficiency

Sapropterin dihydrochloride is the first registered synthetic form of the naturally occurring cofactor and cosubstrate, tetrahydrobiopterin (BH4). It is essential for the conversion of phenylalanine (Phe) by phenylalanine-4-hydroxylase (PAH) to tyrosine. BH4 is also the co-factor of rate-limiting enzymes involved in the synthesis of monoamine neurotransmitters. Phenylketonuria (PKU) is an inherited disorder of PAH, characterized by elevated Phe concentrations (hyperphenylalaninemia) in the blood and brain, with toxic neurological consequences. Sapropterin dihydrochloride is approved for treating patients (of all ages in the USA and >4 years old in Europe) with PKU who are BH4 responsive, and those with BH4 deficiency (Europe). It decreases blood Phe concentration and increases dietary Phe tolerance in some patients with PKU on a low-Phe diet, allowing dietary adjustment or even discontinuation of a low-Phe diet. This article reviews sapropterin dihydrochloride for the management of PKU - aimed at improving clinical outcomes and quality of life - and it considers the potential for incorporating such information into international consensus guidelines.