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Background: Mucopolysaccharidosis type VI or Maroteaux-Lamy syndrome is a rare genetic disorder caused by the deficiency of arylsulphatase B. The resultant accumulation of dermatan sulphate causes lysosomal damage. The clinical symptoms are related to skeletal dysplasia (i.e. short stature and degenerative joint disease). Other manifestations include cardiac disease, impaired pulmonary function, ophthalmological complications, hepatosplenomegaly, sinusitis, otitis, hearing loss and sleep apnea. Intellectual impairment is generally absent. Clinical manifestation is typically by two or three years of age; however, slowly progressive cases may not present until adulthood. Enzyme replacement therapy with galsulfase is considered a new approach for treating mucopolysaccharidosis type VI. Objectives: To evaluate the effectiveness and safety of treating mucopolysaccharidosis VI by enzyme replacement therapy with galsulfase compared to other interventions, placebo or no intervention. Search methods: Eletronic searches were performed on the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, in CENTRAL, MEDLINE, LILACS, the Journal of Inherited Metabolic Disease and ClinicalTrials.gov. Date of the last search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 05 February 2016. Selection criteria: Randomized and quasi-randomized controlled clinical studies of enzyme replacement therapy with galsulfase compared to other interventions or placebo. Data collection and analysis: Two authors independently screened the studies, assessed the risk of bias and extracted data. Main results: One study was included involving 39 participants who received either enzyme replacement therapy with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered to be of overall unclear quality, since the authors did not report how both the allocation generation and concealment were performed. The key finding at 24 weeks in the 12-minute walk test was a statistically significant mean difference of 92.00 meters between the two groups in favour of the galsulfase group (95% confidence interval 11.00 to 172.00). While week 24 results for the three-minute stair climb demonstrated some improvement in the treatment group as compared to the placebo group, this was not significant, mean difference 5.70 (95% confidence interval -0.10 to 11.50). A significant decrease in the urinary glycosaminoglycan levels was observed in favour of the galsulfase group at 24 weeks, mean difference -227.00 (95% confidence interval -264.00 to -190.00). In general, the dose of galsulfase was well tolerated and there were no significant differences in relation to adverse events. These events include drug-related adverse events, serious and severe adverse events, those during infusion, drug-related adverse events during infusion, and deaths. More infusion-related reactions were observed in the galsulfase group and were managed with interruption or slowing of infusion rate or administration of antihistamines or corticosteroids drugs. No deaths occurred during the study. Authors' conclusions: The results of one small study (based on 24-week randomised phase of the study and prior to the open-label extension) demonstrated that galsulfase is more effective than placebo in people with MPS VI, with significant improvements in the 12-minute walk test and a reduction in urinary glycosaminoglycans. There were no significant changes in cardiac or pulmonary functions, liver or spleen volume, overnight apnea-hypopnea, height and weight, quality of life and adverse effects. Further studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy with galsulfase.
Brunelli, M. J., Atallah, Á. N., & da Silva, E. M. (2016, March 4). Enzyme replacement therapy with galsulfase for mucopolysaccharidosis type VI. Cochrane Database of Systematic Reviews. John Wiley and Sons Ltd. https://doi.org/10.1002/14651858.CD009806.pub2