Phenylketonuria (PKU) patients who are deficient in phenylalanine hydroxylase (PAH), and patients with BH4 deficiency, are unable to convert phenylalanine from the diet. PAH hydroxylates phenylalanine through an oxidative reaction with tetrahydrobiopterin (BH4) as co-factor to form tyrosine. Deficiency for either PAH or BH4 can result in high blood phenylalanine levels, which are toxic to the brain and can lead to neurological and behavioural disorders such as lower intelligence, decreased mental concentration, slowed reaction time, depression and phobias. Dietary restrictions in order to minimize phenylalanine intake are difficult to maintain and often cause other deficiencies.
Sapropterin is a synthetic form of cofactor BH4. Excess of cofactor activates residual PAH enzyme, improving phenylalanine metabolism and decreasing phenylalanine concentrations in blood of PKU patients. In patients with BH4 deficiency, sapropterin provides an effective alternative to BH4. PKU patients treated with sapropterin must continue their restricted phenylalanine diet and undergo regular clinical assessment (monitoring of blood phenylalanine and tyrosine levels, nutrient intake, and psycho-motor development).
Sapropterin is indicated for the treatment of hyperphenylalaninaemia in patients with PKU and/or BH4 deficiency who have been shown to be responsive to such treatment.
EPAR of sapropterin.