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Cochrane Database of Systematic Reviews

Sapropterin dihydrochloride for phenylketonuria

Overview of attention for article published in Cochrane database of systematic reviews, March 2015
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Sapropterin dihydrochloride for phenylketonuria
Published in
Cochrane database of systematic reviews, March 2015
DOI 10.1002/14651858.cd008005.pub4
Pubmed ID

Usha Rani Somaraju, Marcus Merrin


Phenylketonuria results from a deficiency of the enzyme phenylalanine hydroxylase. Dietary restriction of phenylalanine keeps blood phenylalanine concentration low. Most natural foods are excluded from diet and supplements are used to supply other nutrients. Recent publications report a decrease in blood phenylalanine concentration in some patients treated with sapropterin dihydrochloride. We examined the evidence for the use of sapropterin dihydrochloride to treat phenylketonuria. This is an update of a previously published Cochrane Review.  OBJECTIVES: To assess the safety and efficacy of sapropterin dihydrochloride in lowering blood phenylalanine concentration in people with phenylketonuria. We identified relevant trials from the Group's Inborn Errors of Metabolism Trials Register. Date of last search: 11 August 2014.We also searched ClinicalTrials.gov and Current controlled trials. Last search: 4 September 2014We contacted the manufacturers of the drug (BioMarin Pharmaceutical Inc.) for information regarding any unpublished trials. Randomized controlled trials comparing sapropterin with no supplementation or placebo in people with phenylketonuria due to phenylalanine hydroxylase deficiency. Two authors independently assessed trials and extracted outcome data. Two placebo-controlled trials were included. One trial administered 10 mg/kg/day sapropterin in 89 children and adults with phenylketonuria whose diets were not restricted and who had previously responded to saproterin.This trial measured change in blood phenylalanine concentration. The second trial screened 90 children (4 to 12 years) with phenylketonuria whose diet was restricted, for responsiveness to sapropterin. Forty-six responders entered the placebo-controlled part of the trial and received 20 mg/kg/day sapropterin. This trial measured change in both phenylalanine concentration and protein tolerance. Both trials reported adverse events. The trials showed an overall low risk of bias; but both are Biomarin-sponsored. One trial showed a significant lowering in blood phenylalanine concentration in the sapropterin group (10 mg/kg/day), mean difference -238.80 μmol/L (95% confidence interval -343.09 to -134.51); a second trial (20 mg/kg/day sapropterin) showed a non-significant difference, mean difference -51.90 μmol/L (95% confidence interval -197.27 to 93.47). The second trial also reported a significant increase in phenylalanine tolerance, mean difference18.00 mg/kg/day (95% confidence interval 12.28 to 23.72) in the 20 mg/kg/day sapropterin group. There is evidence of short-term benefit from using sapropterin in some people with sapropterin-responsive forms of phenylketonuria; blood phenylalanine concentration is lowered and protein tolerance increased. There are no serious adverse events associated with using sapropterin in the short term.There is no evidence on the long-term effects of sapropterin and no clear evidence of effectiveness in severe phenylketonuria.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 172 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 <1%
Netherlands 1 <1%
Unknown 170 99%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 30 17%
Student > Master 25 15%
Researcher 16 9%
Student > Ph. D. Student 15 9%
Other 13 8%
Other 30 17%
Unknown 43 25%
Readers by discipline Count As %
Medicine and Dentistry 52 30%
Nursing and Health Professions 25 15%
Biochemistry, Genetics and Molecular Biology 10 6%
Agricultural and Biological Sciences 9 5%
Pharmacology, Toxicology and Pharmaceutical Science 5 3%
Other 20 12%
Unknown 51 30%