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Introduction: Mucopolysaccharidosis VI (MPS VI) is the result of the absence of arylsulfatase B leading to the abnormal lysosomal accumulation of glycosaminoglycans. Two different phenotypes have been described to date, namely, rapidly progressive and slowly progressive. Aim: To present the evolution of a slowly progressive phenotype of MPS VI in a patient after 2 years of enzyme replacement therapy. Case report: A 26-year-old man diagnosed with MPS VI at 9 years of age started enzyme replacement therapy with galsulfase due to cardiac, pulmonary, neurologic, and joint involvement. After 10 months of treatment, improvement in quality-of-life scales and walk test was evident. Because of persistent symptomatology associated with narrow cervical spinal canal, decompressive surgery was performed. After 2 years of treatment, there was a clear improvement in the respiratory, motor, and cardiac functions as well as in the spinal symptoms. Discussion: The evolution of our patient leads to the conclusion that the combined treatment of galasulfase and decompressive surgery should be indicated at an early stage in order to achieve best outcome for the patient.
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Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease associated with a deficiency or absence of arylsulfatase B leading to the abnormal accumulation of dermatan sulfate. MPS VI shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic spectrum includes skeletal displasia, coarse facies, cardiomyopathy, pulmonary complications and spinal compression. Diagnosis generally requires measurement ofurinary glycosaminoglycans and arylsulfatase B enzyme activity in dried blood spot, leukocytes or cultured fibroblasts. Enzyme replacement therapy (ERT) with galsulfase is now widely available providing improvement in skeletal performance and stabilization in pulmonary and cardiac functioning. Spinal involvement does not respond to ERT when is present, surgical decompression should be indicated early. Prognosis is variable depending on the age of onset and age at initiation of ERT.
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A cross-sectional survey in individuals affected with the lysosomal storage disease Mucopolysaccharidosis VI (MPS VI) was conducted to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of the disease. The survey evaluated 121 bona fide MPS VI-affected individuals over the age of 4 years from 15 countries across the Americas, Europe, and Australasia representing greater than 10% of the estimated world prevalence of the disease. A medical history, complete physical exam, urinary GAG determination, and assessment of several clinical measures related to physical endurance, pulmonary function, joint range of motion, strength, and quality of life were completed for each participant. Although a wide variation in clinical presentation was observed, several general findings were obtained reflecting progression of the disease. Impaired physical endurance, as measured by the distance achieved in a 6-min walk, could be demonstrated across all age groups of MPS VI-affected individuals. High urinary GAG values (>200 mug/mg creatinine) were associated with an accelerated clinical course comprised of age-adjusted short stature and low body weight, impaired endurance, compromised pulmonary function, and reduced joint range of motion. An unexpected result was the predominance of urinary GAG values <100 mug/mg creatinine for those participants over the age of 20 years. Pending the collection of longitudinal data, these results suggest that urinary GAG levels predict clinical morbidity, and longer-term survival is associated with urinary GAG levels below a threshold of 100 mug/mg creatinine.
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Aim: Mucopolysaccharidosis VI (Maroteaux–Lamy syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme N-acetylgalactosamine 4-sulphatase (ASB). Enzyme replacement therapy with recombinant human ASB (rhASB) has been studied in a randomized, double-blind, two-dose (0.2 and 1.0 mg/kg/week) phase I/II study (n=7) followed by an open-label single dose (1.0 mg/kg/week) extension study. We report the pharmacokinetic profile of rhASB and the impact of antibody development. Methods: Pharmacokinetic analysis was performed at weeks 1, 2, 12, 24, 83, 84 and 96. Infusions were administered over 4 hours using a ramp-up protocol. Plasma ASB and rhASB antibody concentrations and urine glycosaminoglycan (GAG) concentrations were determined. Results: The area under the plasma concentration–time curve (AUC0−t) for the high-dose group increased from week 1 to week 2, but remained unchanged at weeks 12 and 24. A large difference in mean AUC0−t was observed between the low- and high-dose groups. Pharmacokinetic results at weeks 83, 84 and 96 were similar to those at week 24. Six patients developed antibodies to rhASB. One patient developed high antibody levels in combination with a high ASB concentration, while a second patient also developed high antibody levels with undetectable ASB concentrations. Antibodies from the second patient blocked detection of ASB. By week 72, antibody levels had decreased in all patients. The high-dose rhASB produced a more rapid and greater percentage reduction in urinary GAG concentrations than the lower dose (70% versus 55% at 24 weeks). Antibody levels did not appear to influence urinary GAG concentrations.