{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T22:52:02Z","timestamp":1772059922030,"version":"3.50.1"},"reference-count":43,"publisher":"American Academy of Pediatrics (AAP)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,6,1]]},"abstract":"<jats:p>Objective. Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome) is a lysosomal storage disease caused by a deficiency of the enzyme N-acetylgalactosamine 4-sulfatase (ASB). This enzyme deficiency leads to a progressive disorder with multiple tissue and organ involvement. The disease is rare and is heterogeneous in its clinical presentation and progression. A potential treatment for this disease exists in the form of enzyme-replacement therapy (ERT) with recombinant human ASB (rhASB), and a phase 1\/2 randomized, double-blind, 2-dose (0.2 and 1 mg\/kg) study in 6 patients showed the treatment at 48 weeks to be well tolerated. Greater biochemical efficacy based on a urine glycosaminoglycan occurred in the high-dose (1 mg\/kg) group, and functional improvement seemed greater in patients in the high-dose group with rapidly advancing disease. On the basis of the phase 1\/2 results, a phase 2, open-label study in patients with rapidly advancing disease was initiated primarily to evaluate efficacy variables that measure endurance, mobility, and joint function in a larger group of patients.<\/jats:p>\n               <jats:p>Methods. This was an open-label, multinational study of 10 MPS VI patients who received 48 weekly intravenous treatments with 1.0 mg\/kg rhASB and had assessments of biochemical and clinical responses at regular intervals.<\/jats:p>\n               <jats:p>Results. After 24 weeks of treatment, each patient on average experienced a 155-m (98%) improvement in the 12-minute walk, a 64-m (62%) improvement at the 6-minute time point of the 12-minute walk, and a 48-stair (110%) gain in the 3-minute stair climb versus the baseline mean values. Additional improvements after 48 weeks of treatment were observed, including mean values of 211 m (138%) in the 12-minute walk, 75 m (80%) at the 6-minute time point of the 12-minute walk, and 61-stair (147%) gain in the 3-minute stair climb versus the baseline mean values. Joint Pain and Stiffness Questionnaire scores improved by at least 50% by week 24 and were maintained at week 48, whereas there were only small improvements in active shoulder range of motion (&amp;lt;10\u00b0) and in the time taken to stand, walk, and turn starting from a seated position (Expanded Timed Get-Up and Go test). Improvement in pulmonary function based on forced vital capacity and forced expiratory volume at 1 minute in the absence of growth was observed in 3 of 6 patients, and the observed gains occurred in the 24- to 48-week treatment interval. A mean decrease of 76% in urinary excretion of glycosaminoglycans indicated that a satisfactory biochemical response was achieved and the ERT was well tolerated.<\/jats:p>\n               <jats:p>Conclusions. The results suggest that a 12-minute walk extends the dynamic range of the conventional 6-minute walk and, along with the 3-minute stair climb, provide a robust approach to documenting the improvement in endurance in MPS VI patients who undergo ERT with rhASB.<\/jats:p>","DOI":"10.1542\/peds.2004-1023","type":"journal-article","created":{"date-parts":[[2005,6,1]],"date-time":"2005-06-01T17:19:46Z","timestamp":1117646386000},"page":"e681-e689","source":"Crossref","is-referenced-by-count":178,"title":["Direct Comparison of Measures of Endurance, Mobility, and Joint Function During Enzyme-Replacement Therapy of Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome): Results After 48 Weeks in a Phase 2 Open-Label Clinical Study of Recombinant Human <i>N<\/i>-Acetylgalactosamine 4-Sulfatase"],"prefix":"10.1542","volume":"115","author":[{"given":"Paul","family":"Harmatz","sequence":"first","affiliation":[{"name":"Children's Hospital & Research Center, Oakland, California"}]},{"given":"David","family":"Ketteridge","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Women's and Children's Hospital Adelaide, North Adelaide, Australia"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[{"name":"Servic\u0327o de Gene\u0301tica Me\u0301dica, Hospital de Cli\u0301nicas de Porto Alegre, Porto Alegre, Brazil"}]},{"given":"Natalie","family":"Guffon","sequence":"additional","affiliation":[{"name":"Ho\u0302pital Edouard Herriot Pavillon S, Maladies Metaboliques, Lyon, France"}]},{"given":"Elisa Lea\u0303o","family":"Teles","sequence":"additional","affiliation":[{"name":"Unidade de Doencas Metabolicas, Departmento Pediatria, Hospital de Sao Joa\u0303o, Porto, Portugal"}]},{"given":"M. Clara Sa\u0301","family":"Miranda","sequence":"additional","affiliation":[{"name":"Instituto de Biologia Moleculare Celular, Porto, Portugal"}]},{"given":"Zi-Fan","family":"Yu","sequence":"additional","affiliation":[{"name":"Statistics Collaborative, Inc, Washington, DC"}]},{"given":"Stuart J.","family":"Swiedler","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical, Inc, Novato, California"}]},{"given":"John J.","family":"Hopwood","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Women's and Children's Hospital Adelaide, North Adelaide, Australia"}]},{"name":"for the MPS VI Study Group","sequence":"additional","affiliation":[]}],"member":"417","published-online":{"date-parts":[[2005,6,1]]},"reference":[{"key":"2021120819232823800_R1","unstructured":"Neufeld EF, Muenzer J. The mucopolysaccharidosis. In: Scriver C, Beaudet AL, Valle D, Sly WS, eds. The Metabolic Basis of Inherited Disease. New York, NY: McGraw-Hill; 2001:4312\u20134352"},{"key":"2021120819232823800_R2","unstructured":"Spranger JW, Koch F, McKusick VA, Natzschka J, Wiedemann HR, Zellweger H. Mucopolysaccharidosis VI (Maroteaux-Lamy's disease). Helv Paediatr Acta.\u20081970;25:337\u2013362"},{"key":"2021120819232823800_R3","unstructured":"Whitley C. The mucopolysaccharidoses. In: Beighton P, ed. McKusick's Heritable Disorders of Connective Tissue. 5th ed. St Louis, MO: CV Mosby; 1993:367\u2013499"},{"key":"2021120819232823800_R4","doi-asserted-by":"crossref","unstructured":"Fong LV, Menahem S, Wraith JE, Chow CW. Endocardial fibroelastosis in mucopolysaccharidosis type VI. Clin Cardiol.\u20081987;10:362\u2013364","DOI":"10.1002\/clc.4960100612"},{"key":"2021120819232823800_R5","doi-asserted-by":"crossref","unstructured":"Hayflick S, Rowe S, Kavanaugh-McHugh A, Olson JL, Valle D. Acute infantile cardiomyopathy as a presenting feature of mucopolysaccharidosis VI. J Pediatrics.\u20081992;120:269\u2013272","DOI":"10.1016\/S0022-3476(05)80441-X"},{"key":"2021120819232823800_R6","doi-asserted-by":"crossref","unstructured":"Pilz H, von Figura K, Goebel HH. Deficiency of arylsulfatase B in 2 brothers aged 40 and 38 years (Maroteaux-Lamy syndrome, type B). Ann Neurol.\u20081979;6:315\u2013325","DOI":"10.1002\/ana.410060405"},{"key":"2021120819232823800_R7","doi-asserted-by":"crossref","unstructured":"Tonnesen T, Gregersen HN, Guttler F. Normal MPS excretion, but dermatan sulphaturia, combined with a mild Maroteaux-Lamy phenotype. J Med Genet.\u20081991;28:499\u2013501","DOI":"10.1136\/jmg.28.7.499"},{"key":"2021120819232823800_R8","doi-asserted-by":"crossref","unstructured":"Hoogerbrugge PM, Brouwer OF, Bordigoni P, et al. Allogeneic bone marrow transplantation for lysosomal storage diseases. The European Group for Bone Marrow Transplantation. 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