Improving sapropterin administration efficacy in PKU: Clinical practice case studies

In patients with phenylketonuria (PKU), sapropterin dihydrochloride (sapropterin) lowers blood phenylalanine (Phe) and may enhance Phe tolerance in sapropterin responsive patients. Attention to its administration, particularly the timing, and giving it with food with appropriate macronutrient composition, is important. We describe two boys with PKU who improved their Phe tolerance and metabolic control when they adjusted their method of sapropterin administration. Case 1: aged 7.25 years with mild PKU experienced a 40 % reduction in blood Phe after a 30-day sapropterin trial (20 mg/kg). Initially, he took sapropterin once daily dissolved in water. This increased his protein tolerance from 26 g to 50 g/day and reduced his protein equivalent from protein substitute to 20 g/day. His blood Phe was a median of 230 μmol/L (range: 130–300). After six months, twice-daily dosing further improved his protein tolerance to 60 g/day, with a lower median blood Phe (130 μmol/L, range: 80–220). By age 8 years, he swallowed tablets intact with meals, ate an unrestricted protein intake (∼80 g/day), stopped protein substitute, maintained excellent metabolic control with perceived cognitive improvement. Case 2: a boy who aged 4.992 years with mild PKU had a 33 % reduction in blood Phe after a 30-day sapropterin (20 mg/kg) trial. Initially, he took sapropterin once daily dissolved in water, increasing his protein tolerance from 14 g to 55 g/day, and reducing protein equivalent from protein substitute to 20 g/day. Median blood Phe was 240 μmol/L (range: 120–320). At age 6.92 years, twice-daily dosing and swallowing intact tablets further lowered his blood Phe, to a mean of 130 μmol/L (range: 100–130). He stopped dietary protein restriction and protein substitute intake. These case studies showed clinical and dietary benefits with adjustment of sapropterin administration. It was unclear if the improvements observed were associated with twice daily sapropterin administration, attention to taking it with fat containing meals, swallowing the tablets intact, or a combination of these. Further research to monitor the efficacy and safety of administration change is necessary.