Mucopolysaccharidosis type VI (MPS 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 (ERT) with galsulfase is considered a new approach for treating MPS VI. To evaluate the effectiveness and safety of treating MPS VI by ERT with galsulfase compared to other interventions, placebo or no intervention. Eletronic searches were performed on the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Date of the latest search:  09 June 2021. Further searches of the following databases were also performed: CENTRAL, MEDLINE, LILACS, the Journal of Inherited Metabolic Disease, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Date of the latest search: 20 August 2021. Randomized and quasi-randomized controlled clinical studies of ERT with galsulfase compared to other interventions or placebo. Two authors independently screened the studies, assessed the risk of bias, extracted data and assessed the certainty of the the evidence using the GRADE criteria. One study was included involving 39 participants who received either ERT with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered overall to have an unclear risk of bias in relation to the design and implementation of the study, since the authors did not report how both the allocation generation and concealment were performed. Given the very low certainty of the evidence, we are uncertain whether at 24 weeks there was a difference between groups in relation to the 12-minute walk test, mean difference (MD) of 92.00 meters (95% confidence interval (CI) 11.00 to 172.00), or the three-minute stair climb, MD 5.70 (95% CI -0.10 to 11.50). In relation to respiratory tests, we are uncertain whether galsulfase makes any difference as compared to placebo in forced vital capacity in litres (FVC (L) (absolute change in baseline), given the very low certainty of the evidence. Cardiac function was not reported in the included study. We found that galsulfase, as compared to placebo, may decrease urinary glycosaminoglycan levels at 24 weeks, MD -227.00 (95% CI -264.00 to -190.00) (low-certainty evidence). We are uncertain whether there are differences between the galsulfase and placebo groups in relation to adverse events (very low-certainty evidence). In general, the dose of galsulfase was well tolerated and there were no differences between groups. 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 this review are based only on one small study (a 24-week randomised phase of the study and prior to the open-label extension). We are uncertain whether galsulfase is more effective than placebo, for treating people with MPS VI, in relation to the 12-minute walk test or the three-minute stair climb, as the certainty of the evidence has been assessed as very low. We found that galsulfase may reduce urinary glycosaminoglycans levels. We are also uncertain whether there are any differences between treatment groups in relation to 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 ERT with galsulfase.

Mucopolysaccharidosis VI (MPS VI), or Maroteaux-Lamy syndrome, is an autosomal recessive lysosomal storage disorder caused by deficient activity of the enzyme arylsulfatase B (ASB). Progressive accumulation of glycosaminoglycans (GAGs) in organs and tissues leads to the development of multisystem clinical manifestations. The presentation of MPS VI is genotypically and phenotypically diverse, with a large number of potential disease-causing mutations and a phenotypic spectrum ranging from very slowly to very rapidly progressing disease. Diagnosis of MPS VI relies on presence of clinical features, increased GAG levels in urine or low ASB activity in dried blood spots, and measurement of enzyme activity levels in leukocytes or fibroblasts. The management of MPS VI involves enzyme replacement therapy and medical and surgical treatment of disease manifestations. Liquid chromatography/tandem mass spectrometry of GAG-derived disaccharides in blood or urine is emerging as a valuable method in the diagnosis, prognosis and assessment of therapeutic efficacy in MPS VI.

Mucopolysaccharidosis (MPS) VI is an autosomal recessive lysosomal storage disorder arising from deficient activity of N-acetylgalactosamine-4-sulfatase (arylsulfatase B) and subsequent intracellular accumulation of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin-4-sulfate. Manifestations are multi-systemic and include skeletal abnormalities such as dysostosis multiplex and short stature. Reference height-for-age growth charts for treatment-naïve MPS VI patients have been published for both the slowly and rapidly progressing populations. Categorization of disease progression for these charts was based on urinary GAG (uGAG) level; high (>200μg/mg creatinine) levels identified subjects as rapidly progressing. Height data for 141 patients who began galsulfase treatment by the age of 18years were collected and stratified by baseline uGAG level and age at ERT initiation in 3-year increments. The reference MPS VI growth charts were used to calculate change in Z-score from pre-treatment baseline to last follow-up. Among patients with high baseline uGAG levels, galsulfase ERT was associated with an increase in Z-score for those beginning treatment at 0-3, >3-6, >6-9, >9-12, and >12-15years of age (p<0.05). Increases in Z-score were not detected for patients who began treatment between 15 and 18years of age, nor for patients with low (≤200μg/mg creatinine) baseline uGAG levels, regardless of age at treatment initiation. The largest positive deviation from untreated reference populations was seen in the high uGAG excretion groups who began treatment by 6years of age, suggesting an age- and severity-dependent impact of galsulfase ERT on growth.

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. To evaluate the effectiveness and safety of treating mucopolysaccharidosis VI by enzyme replacement therapy with galsulfase compared to other interventions, placebo or no intervention. 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. Randomized and quasi-randomized controlled clinical studies of enzyme replacement therapy with galsulfase compared to other interventions or placebo. Two authors independently screened the studies, assessed the risk of bias and extracted data. 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. 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.