{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T22:07:36Z","timestamp":1764194856173,"version":"3.37.3"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical","doi-asserted-by":"publisher","award":["Ultragenyx Pharmaceutical"],"award-info":[{"award-number":["Ultragenyx Pharmaceutical"]}],"id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of \u03b2-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (<jats:italic>N<\/jats:italic>\u2009\u2248\u200950 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+\u20093%, -32%, and \u2212\u200941%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03176-z","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T14:01:54Z","timestamp":1715090514000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-3686","authenticated-orcid":false,"given":"Roberto","family":"Giugliani","sequence":"first","affiliation":[]},{"given":"Antonio","family":"Gonzalez-Meneses","sequence":"additional","affiliation":[]},{"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[]},{"given":"Barbara","family":"Burton","sequence":"additional","affiliation":[]},{"given":"Raymond","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[]},{"given":"Esmeralda","family":"Oussoren","sequence":"additional","affiliation":[]},{"given":"Julia B.","family":"Hennermann","sequence":"additional","affiliation":[]},{"given":"Brigitte","family":"Chabrol","sequence":"additional","affiliation":[]},{"given":"Christina L.","family":"Grant","sequence":"additional","affiliation":[]},{"given":"Angela","family":"Sun","sequence":"additional","affiliation":[]},{"given":"Consuelo","family":"Durand","sequence":"additional","affiliation":[]},{"given":"Joel","family":"Hetzer","sequence":"additional","affiliation":[]},{"given":"Betsy","family":"Malkus","sequence":"additional","affiliation":[]},{"given":"Deborah","family":"Marsden","sequence":"additional","affiliation":[]},{"given":"J. Lawrence","family":"Merritt II","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"issue":"2","key":"3176_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/S0022-3476(73)80162-3","volume":"82","author":"WS Sly","year":"1973","unstructured":"Sly WS, et al. Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis. J Pediatr. 1973;82(2):249\u201357.","journal-title":"J Pediatr"},{"issue":"1","key":"3176_CR2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1001\/archpedi.1985.02140030059029","volume":"139","author":"JE Lee","year":"1985","unstructured":"Lee JE, et al. Beta-glucuronidase deficiency. A heterogeneous mucopolysaccharidosis. Am J Dis Child. 1985;139(1):57\u20139.","journal-title":"Am J Dis Child"},{"key":"3176_CR3","unstructured":"Orphanet. Orphanet Rare Diseases Collection. Prevalence distribution of rare diseases: bibliographic data. May 2019. https:\/\/www.orpha.net\/consor\/cgi-bin\/Disease_Search.php?lng=EN&data_id=40&Disease_Disease_Search_diseaseGroup=mpsVII&Disease_Disease_Search_diseaseType=Pat&Disease(s)\/group%20of%20diseases=Mucopolysaccharidosis-type7&title=Mucopolysaccharidosis%20type%207&search=Disease_Search_Simple. Accessed 02 June 2023."},{"issue":"6","key":"3176_CR4","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1136\/jmedgenet-2015-103322","volume":"53","author":"AM Montano","year":"2016","unstructured":"Montano AM, et al. Clinical course of sly syndrome (mucopolysaccharidosis type VII). J Med Genet. 2016;53(6):403\u201318.","journal-title":"J Med Genet"},{"issue":"2","key":"3176_CR5","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/ajmg.1320440206","volume":"44","author":"RD de Kremer","year":"1992","unstructured":"de Kremer RD, et al. Mucopolysaccharidosis type VII (beta-glucuronidase deficiency): a chronic variant with an oligosymptomatic severe skeletal dysplasia. Am J Med Genet. 1992;44(2):145\u201352.","journal-title":"Am J Med Genet"},{"issue":"3","key":"3176_CR6","first-page":"457","volume":"58","author":"R Vervoort","year":"1996","unstructured":"Vervoort R, et al. Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII. Am J Hum Genet. 1996;58(3):457\u201371.","journal-title":"Am J Hum Genet"},{"issue":"4","key":"3176_CR7","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.ymgme.2018.02.006","volume":"123","author":"P Harmatz","year":"2018","unstructured":"Harmatz P, et al. A novel Blind Start study design to investigate vestronidase alfa for mucopolysaccharidosis VII, an ultra-rare genetic disease. Mol Genet Metab. 2018;123(4):488\u201394.","journal-title":"Mol Genet Metab"},{"issue":"3","key":"3176_CR8","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.ymgme.2020.01.003","volume":"129","author":"RY Wang","year":"2020","unstructured":"Wang RY, et al. The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII. Mol Genet Metab. 2020;129(3):219\u201327.","journal-title":"Mol Genet Metab"},{"issue":"1","key":"3176_CR9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ymgme.2020.02.006","volume":"130","author":"E Kakkis","year":"2020","unstructured":"Kakkis E, Marsden D. Urinary glycosaminoglycans as a potential biomarker for evaluating treatment efficacy in subjects with mucopolysaccharidoses. Mol Genet Metab. 2020;130(1):7\u201315.","journal-title":"Mol Genet Metab"},{"issue":"4","key":"3176_CR10","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.jpeds.2006.12.052","volume":"150","author":"R Geiger","year":"2007","unstructured":"Geiger R, et al. Six-minute walk test in children and adolescents. J Pediatr. 2007;150(4):395\u20139.","journal-title":"J Pediatr"},{"issue":"2","key":"3176_CR11","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1097\/00008483-200103000-00005","volume":"21","author":"WJ Gibbons","year":"2001","unstructured":"Gibbons WJ, et al. Reference values for a multiple repetition 6-minute walk test in healthy adults older than 20 years. J Cardiopulm Rehabil. 2001;21(2):87\u201393.","journal-title":"J Cardiopulm Rehabil"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03176-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03176-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03176-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T14:07:26Z","timestamp":1715090846000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03176-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3176"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03176-z","relation":{},"ISSN":["1750-1172"],"issn-type":[{"type":"electronic","value":"1750-1172"}],"subject":[],"published":{"date-parts":[[2024,5,7]]},"assertion":[{"value":"17 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The protocol was reviewed and approved by the institutional review boards at respective sites. Prior to any research-related procedures, participants provided written informed consent or, in the case of participants\u2009<\u200918 years of age (or 16 years, depending on the region) or participants\u2009>\u200918 years of age with cognitive deficiencies, provided written assent (if required), with written informed consent provided by a legally authorized representative after the nature of the DMP had been explained.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors approved the manuscript for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Joel Hetzer, Betsy Malkus, Deborah Marsden, and J. Lawrence Merritt II are employees and shareholders of Ultragenyx Pharmaceutical Inc.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"189"}}