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 10-20mg/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 7years.Case 1: Female, currently age 20. Genotype p. 165T/p/F39L, c.[194T>C]; [117C>G]. Newborn Phe: 851μmol/L. Pre-Sapropterin Phe tolerance: 600mgPhe/day to maintain Phe levels <400μmol/L. Commenced on Sapropterin 400mg (6.5mg/kg/day) with increase in Phe tolerance to 800mg/day.Case 2: Female, currently age 23. Genotype p. 165T/pF39L; c.[194T>C]; [117C>G]. Newborn Phe: 714μmol/L. Pre-Sapropterin Phe tolerance: 700mgPhe/day. Commenced on Sapropterin 400mg (8mg/kg/day) with increase in Phe tolerance to 800mg/day.Case 3: Male, currently age 22. Genotype p. 165T/p.S349P; c.[194T>C][1045T>C]. Newborn Phe: 1,036μmol/L. Pre-Sapropterin Phe tolerance: 600mg Phe/day. Commenced on Sapropterin 400mg (5.4mg/kg/day). Increased to 1,600mgPhe/day.Case 4: Female, currently age 29. Genotype p.R408W/p/p.Y414C; c.[1222C>T], [1241A>G]. Newborn Phe: 1,600μmol/L. Pre-Sapropterin tolerance: 450mg/day. Commenced on Sapropterin 400mg (5.0mg/kg/day). Increased to 900mgPhe/day.Almost 7years of surveillance for these four patients has shown that this dose of Sapropterin (range 5-8mg/kgday) was well tolerated and effective with a significant response to treatment and a marked improvement in quality of life at these lower Sapropterin doses.