{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:47:41Z","timestamp":1785491261694,"version":"3.56.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004339","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>Acid sphingomyelinase deficiency (ASMD) is a rare, progressive, potentially fatal lysosomal storage disease that exhibits a broad spectrum of clinical phenotypes. There is a need to expand the knowledge of disease mortality and morbidity in Germany because of limited information on survival analysis in patients with chronic ASMD (type B or type A\/B).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This observational, multicentre, retrospective cohort study was conducted using medical records of patients with the first symptom onset\/diagnosis of ASMD type B or type A\/B between 1st January 1990 and 31st July 2021 from four German medical centres. Eligible medical records were abstracted to collect data on demographic characteristics, medical history, hospitalisation, mortality, and causes of death from disease onset to the last follow-up\/death. Survival outcomes were estimated using the Kaplan\u2013Meier analysis. Standardised mortality ratio (SMR) was also explored.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>This study included 33 chart records of patients with ASMD type B (<jats:italic>n<\/jats:italic>\u2009=\u200924) and type A\/B (<jats:italic>n<\/jats:italic>\u2009=\u20099), with a median (interquartile range [IQR]) age of 8.0 [3.0\u201320.0] years and 1.0 [1.0\u20132.0] years, respectively, at diagnosis. The commonly reported manifestations were related to spleen (100.0%), liver (93.9%), and respiratory (77.4%) abnormalities. Nine deaths were reported at a median [IQR] age of 17.0 [5.0\u201325.0] years, with 66.7% of overall patients deceased at less than 18 years of age; the median [IQR] age at death for patients with ASMD type B (<jats:italic>n<\/jats:italic>\u2009=\u20094) and type A\/B (<jats:italic>n<\/jats:italic>\u2009=\u20095) was 31.0 [11.0\u201355.0] and 9.0 [4.0\u201318.0] years, respectively. All deaths were ASMD-related and primarily caused by liver or respiratory failures or severe progressive neurodegeneration (two patients with ASMD type A\/B). The median (95% confidence interval [CI]) overall survival age since birth was 45.4 (17.5\u201365.0) years. Additionally, an SMR [95% CI] analysis (21.6 [9.8\u201338.0]) showed that age-specific deaths in the ASMD population were 21.6 times more frequent than that in the general German population.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study highlights considerable morbidity and mortality associated with ASMD type B and type A\/B in Germany. It further emphasises the importance of effective therapy for chronic ASMD to reduce disease complications.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03174-1","type":"journal-article","created":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T04:01:28Z","timestamp":1712980888000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A retrospective study of morbidity and mortality of chronic acid sphingomyelinase deficiency in Germany"],"prefix":"10.1186","volume":"19","author":[{"given":"Eugen","family":"Mengel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Muschol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Weinhold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasia","family":"Ziagaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Neugebauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benno","family":"Antoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Langer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Gasparic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Guillonneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Fournier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Laredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-960X","authenticated-orcid":false,"given":"Ruth","family":"Pulikottil-Jacob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"3174_CR1","doi-asserted-by":"publisher","first-page":"e672","DOI":"10.1542\/peds.2004-0887","volume":"114","author":"MP Wasserstein","year":"2004","unstructured":"Wasserstein MP, Desnick RJ, Schuchman EH, Hossain S, Wallenstein S, Lamm C, et al. The natural history of type B niemann-pick disease: results from a 10-year longitudinal study. Pediatrics. 2004;114:e672\u20137.","journal-title":"Pediatrics"},{"key":"3174_CR2","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.beem.2014.10.002","volume":"29","author":"EH Schuchman","year":"2015","unstructured":"Schuchman EH, Wasserstein MP. Types a, B Niemann-pick disease. Best Pract Res Clin Endocrinol Metab. 2015;29:237\u201347.","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"3174_CR3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ymgme.2016.12.008","volume":"120","author":"EH Schuchman","year":"2017","unstructured":"Schuchman EH, Desnick RJ. Types a, B Niemann-pick disease. 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Drugs. 2022;82:941\u20137.","journal-title":"Drugs"},{"key":"3174_CR13","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1186\/s13023-022-02587-0","volume":"17","author":"GA Diaz","year":"2022","unstructured":"Diaz GA, Giugliani R, Guffon N, Jones SA, Mengel E, Scarpa M, et al. Long-term safety and clinical outcomes of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency: two-year results. Orphanet J Rare Dis. 2022;17:437.","journal-title":"Orphanet J Rare Dis"},{"key":"3174_CR14","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1038\/s41436-021-01156-3","volume":"23","author":"GA Diaz","year":"2021","unstructured":"Diaz GA, Jones SA, Scarpa M, Mengel KE, Giugliani R, Guffon N, et al. One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. 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Orphanet J Rare Dis. 2023;18:85.","journal-title":"Orphanet J Rare Dis"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03174-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03174-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03174-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T04:01:56Z","timestamp":1712980916000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03174-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,13]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3174"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03174-1","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,13]]},"assertion":[{"value":"1 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":"13 April 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":"This study was conducted in accordance with the Declaration of Helsinki and all subsequent amendments, the guidelines for Good Epidemiological Practice, and Good Pharmacoepidemiology Practices issued by the International Society for Pharmacoepidemiology. All study documents were reviewed by the leading Ethics Committee (Landes\u00e4rztekammer Hessen) and the Local Ethics Committee (\u00c4rztekammer Hamburg). The committees had no concerns about the conduct of the study. No additional local review was needed for sites located in Berlin. All patients and\/or patients\u2019 parents\/legal guardians provided informed consent or assent to participate in the study. For data collection from deceased patients, an informed consent waiver was used.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"EM has received research grants, speakers\u2019 honoraria, and consultation fees from Sanofi, Takeda, Orphazyme, Avrobio, Idorsia, Cyclo Therapeutics, Alexion, and Amicus. NM has received research grants, speakers\u2019 honoraria, and\/or consultation fees from Sanofi, Takeda, Amicus, Chiesi, JCR, and Lysogene. NW has received research grants, speakers\u2019 honoraria, travel grants, and\/or consultation fees from Sanofi, Takeda, and Biomarin. AZ has received speakers\u2019 honoraria and consultation fees from Sanofi, Genzyme, Takeda, and Biomarin. JN has received travel grants from Sanofi, Takeda, and Biomarin. BA and LL are employees of IQVIA. MG, SG, MF, and RPJ are employees and may hold stock and\/or stock options in Sanofi. FL was an employee of Sanofi at the time of study conduct.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"161"}}