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Sapropterin dihydrochloride for phenylketonuria
Usha Rani Somaraju1, Marcus Merrin
1Department of Biochemistry, Malla Reddy Medical College for Women, Suraram Main Road, Jeedimetla Qutbullapur Municipality, Hyderabad, India, 500 055.
The Cochrane Database of Systematic Reviews
|March 28, 2015
Summary
Sapropterin dihydrochloride shows short-term benefits for phenylketonuria (PKU) by lowering blood phenylalanine levels and increasing protein tolerance in responsive patients. Further research is needed for long-term efficacy and severe PKU cases.
Area of Science:
- Metabolic Disorders
- Pharmacological Interventions
- Genetic Diseases
Background:
- Phenylketonuria (PKU) is a genetic disorder caused by phenylalanine hydroxylase deficiency, necessitating strict dietary phenylalanine restriction.
- Sapropterin dihydrochloride has emerged as a potential therapeutic agent, with recent studies indicating its ability to reduce blood phenylalanine concentrations.
- This review updates previous findings on the efficacy and safety of sapropterin dihydrochloride for PKU management.
Purpose of the Study:
- To evaluate the safety and efficacy of sapropterin dihydrochloride in reducing blood phenylalanine levels in individuals with phenylketonuria (PKU).
- To assess the impact of sapropterin dihydrochloride on protein tolerance in PKU patients.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) comparing sapropterin dihydrochloride with placebo or no supplementation in PKU patients.
- Searches conducted across multiple trial registers and manufacturer outreach for unpublished data (last search September 2014).
- Independent data extraction and risk of bias assessment by two authors.
Main Results:
- Two placebo-controlled trials were included, one with 89 participants (unrestricted diet) and another screening 90 children (restricted diet), with 46 responders entering the placebo phase.
- One trial demonstrated a significant reduction in blood phenylalanine levels with 10 mg/kg/day sapropterin (mean difference -238.80 μmol/L).
- The second trial showed a non-significant reduction in phenylalanine levels with 20 mg/kg/day sapropterin but a significant increase in phenylalanine tolerance (mean difference 18.00 mg/kg/day).
Conclusions:
- Sapropterin dihydrochloride offers short-term benefits for certain phenylketonuria patients, including lowered blood phenylalanine and increased protein tolerance.
- No serious adverse events were reported with short-term sapropterin dihydrochloride use.
- Evidence regarding long-term effects and efficacy in severe PKU remains limited.
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