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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, Harmony Hall, Prospect, Kingstown, St.Vincent, Saint Vincent and The Grenadines, P. O. Box 1669.
The Cochrane Database of Systematic Reviews
|June 18, 2010
Summary
Sapropterin dihydrochloride shows short-term benefits for phenylketonuria patients, lowering blood phenylalanine and increasing protein tolerance. Further research is needed for long-term effects and severe cases.
Area of Science:
- Biochemistry
- Genetics
- Metabolic Disorders
Background:
- Phenylketonuria (PKU) is a genetic disorder caused by phenylalanine hydroxylase deficiency.
- Dietary management of PKU involves strict phenylalanine restriction.
- Sapropterin dihydrochloride is being investigated as a potential therapeutic agent for PKU.
Purpose of the Study:
- To evaluate the safety and efficacy of sapropterin dihydrochloride in reducing blood phenylalanine levels in PKU patients.
- To assess the impact of sapropterin dihydrochloride on phenylalanine tolerance.
Main Methods:
- Systematic review of randomized controlled trials (RCTs) identified through multiple databases and manufacturer outreach.
- Two RCTs were included: one with 89 participants (unrestricted diet) and another with 46 responders (restricted diet).
- Outcomes assessed included changes in blood phenylalanine concentration and protein tolerance; adverse events were also recorded.
Main Results:
- One trial showed a significant reduction in blood phenylalanine with 10 mg/kg/day sapropterin (mean difference -238.80 mumol/L).
- A second trial using 20 mg/kg/day sapropterin demonstrated a significant increase in phenylalanine tolerance (mean difference 18.00 mg/kg/day) but a non-significant reduction in phenylalanine levels.
- 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 phenylketonuria, including lower phenylalanine levels and increased protein tolerance.
- No serious adverse events were observed with short-term sapropterin dihydrochloride use.
- Evidence regarding long-term effects and efficacy in severe PKU remains limited.
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