Extended experience of lower dose sapropterin in irish adults with mild phenylketonuria

Abstract

Adherence to dietary and treatment recommendations is a long-standing concern for adults and adolescents with PKU and treating clinicians. In about 20–30% of PKU patients, Phe levels may be controlled by tetrahydrobiopterin (BH4) therapy. The European PKU 2017 Guidelines recommends treatment with BH4 for cases of proven long-term BH4 responsiveness, with a recommended dosage of Sapropterin 10–20 mg/kg/day. We report four young Irish patients with mild PKU, known to be BH4 responsive, who were treated with lower doses of Sapropterin for over 7 years. Case 1: Female, currently age 20. Genotype p. 165T/p/F39L, c.[194T>C]; [117C>G]. Newborn Phe: 851 μmol/L. Pre-Sapropterin Phe tolerance: 600 mg Phe/day to maintain Phe levels <400 μmol/L. Commenced on Sapropterin 400 mg (6.5 mg/kg/day) with increase in Phe tolerance to 800 mg/day. Case 2: Female, currently age 23. Genotype p. 165T/pF39L; c.[194T>C]; [117C>G]. Newborn Phe: 714 μmol/L. Pre-Sapropterin Phe tolerance: 700 mg Phe/day. Commenced on Sapropterin 400 mg (8 mg/kg/day) with increase in Phe tolerance to 800 mg/day. Case 3: Male, currently age 22. Genotype p. 165T/p.S349P; c.[194T>C][1045T>C]. Newborn Phe: 1,036 μmol/L. Pre-Sapropterin Phe tolerance: 600 mg Phe/day. Commenced on Sapropterin 400 mg (5.4 mg/kg/day). Increased to 1,600 mg Phe/day. Case 4: Female, currently age 29. Genotype p.R408W/p/p.Y414C; c.[1222C>T], [1241A>G]. Newborn Phe: 1,600 μmol/L. Pre-Sapropterin tolerance: 450 mg/day. Commenced on Sapropterin 400 mg (5.0 mg/kg/day). Increased to 900 mg Phe/day. Almost 7 years of surveillance for these four patients has shown that this dose of Sapropterin (range 5–8 mg/kg day) was well tolerated and effective with a significant response to treatment and a marked improvement in quality of life at these lower Sapropterin doses.