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Genetic Incorporation of Biosynthesized L-dihydroxyphenylalanine (DOPA) and Its Application to Protein Conjugation
Published on: August 24, 2018
Sapropterin dihydrochloride for phenylketonuria
Usha Rani Somaraju1, Marcus Merrin
1Department of Biochemistry and Genetics, Trinity School of Medicine, Kingstown, Saint Vincent and The Grenadines. dr_usha_rani@yahoo.com.
The Cochrane Database of Systematic Reviews
|December 14, 2012
Summary
Sapropterin dihydrochloride shows short-term benefits for phenylketonuria (PKU) by lowering blood phenylalanine levels and improving protein tolerance in responsive patients. No serious adverse events were noted in short-term use.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Phenylketonuria (PKU) is a genetic disorder caused by phenylalanine hydroxylase deficiency.
- Dietary phenylalanine restriction is the primary treatment, necessitating nutrient supplements.
- Sapropterin dihydrochloride is being investigated for its potential to lower blood phenylalanine levels.
Purpose of the Study:
- To evaluate the safety and efficacy of sapropterin dihydrochloride in reducing blood phenylalanine concentrations in individuals with PKU.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) identified through specialized registers and clinical trial databases.
- Two RCTs were included: one with 89 participants (unrestricted diet) and another screening 90 children (restricted diet) followed by a placebo-controlled phase with 46 responders.
- Data extraction and assessment were performed independently by two authors; drug manufacturer information was also sought.
Main Results:
- One trial showed a significant reduction in blood phenylalanine with sapropterin (10 mg/kg/day), mean difference -238.80 μmol/L.
- A second trial (20 mg/kg/day) demonstrated a significant increase in phenylalanine tolerance (mean difference 18.00 mg/kg/day) but a non-significant reduction in blood phenylalanine.
- Both trials reported adverse events, with an overall low risk of bias, though both were sponsored by the drug manufacturer.
Conclusions:
- Sapropterin dihydrochloride offers short-term benefits for some patients with sapropterin-responsive PKU, including lower phenylalanine levels and increased protein tolerance.
- No serious adverse events were associated with short-term sapropterin use.
- Long-term efficacy and effectiveness in severe PKU remain unproven.
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