{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:34:27Z","timestamp":1791434067873,"version":"4.3.3"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100016198","name":"Idorsia Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016198","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>The GM1 and GM2 gangliosidoses and type 2 Gaucher disease (GD2) are inherited lysosomal storage disorders with most cases having symptom onset in infancy and reduced life expectancy. The conditions are rare, and there is therefore a need for accurate and up to date information concerning the disease course and survival to assist in the design of clinical trials. RETRIEVE is a natural history study aiming to: (1) collect data on the survival of patients with early-onset (onset of first neurological manifestation before 24\u00a0months of age) GM1, GM2, or GD2; (2) collect data that could constitute a historical control group for future clinical trials; and (3) evaluate whether the conditions can be assessed together in a single interventional clinical trial. Group A included patients who were deceased or with unknown survival status at enrollment and was thus limited to retrospective data. Group B included patients who were alive at enrollment, who were followed prospectively with additional retrospective data collection.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Group A included 185 patients (60 with GM1, 78 with GM2, and 47 with GD2), and Group B included 40 patients (18 with GM1, 16 with GM2, and 6 with GD2). Mean and median age at diagnosis and age at onset of first neurological manifestation were youngest in patients with GD2 and oldest in patients with GM2 in both groups. In Group A, median (95% CI) survival was 19.0 (18.0, 22.0), 44.0 (37.0, 51.9) and 14.0 (10.0, 16.0) months in patients with GM1, GM2 and GD2, respectively. In Group B, hypotonia was experienced by most patients with GM1 (17\/18, 94.4%), and was less common in patients with GM2 (12\/16, 75.0%) and GD2 (4\/6, 66.7%). Strabismus and splenomegaly were reported in all six patients with GD2.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>RETRIEVE is one of the largest natural history studies of GM1, GM2, and GD2. Results were generally consistent with the published literature, with differences potentially due to variation in inclusion criteria. The difference in median survival between patients with early-onset GM1, GM2, and GD2 reported in this study suggests that the three diseases should not be pooled for study in clinical trials.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-024-03409-1","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T10:24:52Z","timestamp":1733394292000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A natural history study of pediatric patients with early onset of GM1 gangliosidosis, GM2 gangliosidoses, or gaucher disease type 2 (RETRIEVE)"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7707-4521","authenticated-orcid":false,"given":"B\u00e9n\u00e9dicte","family":"H\u00e9ron","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyros","family":"Batzios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Mengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Gautschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Cornelisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luba","family":"Trokan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Schwierin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Rohrbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"issue":"5","key":"3409_CR1","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.bbalip.2013.10.015","volume":"1841","author":"H Schulze","year":"2014","unstructured":"Schulze H, Sandhoff K. Sphingolipids and lysosomal pathologies. Biochim Biophys Acta. 2014;1841(5):799\u2013810.","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"3409_CR2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.ymgme.2017.04.011","volume":"121","author":"JR Jarnes Utz","year":"2017","unstructured":"Jarnes Utz JR, Kim S, King K, Ziegler R, Schema L, Redtree ES, et al. Infantile gangliosidoses: mapping a timeline of clinical changes. Mol Genet Metab. 2017;121(2):170\u20139.","journal-title":"Mol Genet Metab"},{"key":"3409_CR3","first-page":"663","volume":"13","author":"DS Regier","year":"2016","unstructured":"Regier DS, Proia RL, D\u2019Azzo A, Tifft CJ. The GM1 and GM2 gangliosidoses: natural history and progress toward therapy. Pediatr Endocrinol Rev. 2016;13:663\u201373.","journal-title":"Pediatr Endocrinol Rev"},{"issue":"5","key":"3409_CR4","doi-asserted-by":"publisher","first-page":"e1233","DOI":"10.1542\/peds.2011-0078","volume":"128","author":"AE Bley","year":"2011","unstructured":"Bley AE, Giannikopoulos OA, Hayden D, Kubilus K, Tifft CJ, Eichler FS. Natural history of infantile GM2 gangliosidosis. Pediatrics. 2011;128(5):e1233\u201341.","journal-title":"Pediatrics"},{"issue":"1\u20132","key":"3409_CR5","first-page":"1","volume":"2","author":"CR Ferreira","year":"2017","unstructured":"Ferreira CR, Gahl WA. Lysosomal storage diseases. Transl Sci Rare Dis. 2017;2(1\u20132):1\u201371.","journal-title":"Transl Sci Rare Dis"},{"issue":"3","key":"3409_CR6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ymgme.2019.12.012","volume":"129","author":"FM Lang","year":"2020","unstructured":"Lang FM, Korner P, Harnett M, Karunakara A, Tifft CJ. 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Mol Genet Metab. 2008;94(4):391\u20136.","journal-title":"Mol Genet Metab"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03409-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-024-03409-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-024-03409-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T11:07:28Z","timestamp":1733396848000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-024-03409-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":14,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3409"],"URL":"https:\/\/doi.org\/10.1186\/s13023-024-03409-1","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,5]]},"assertion":[{"value":"18 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 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 study was conducted in compliance with Good Epidemiology Practice guidelines, the ethical principles arising from the Declaration of Helsinki revised in 2013, and all current local regulations. Ethics Committee\/Institutional Review Board approval was obtained as required by applicable site policies, national privacy regulations and other state and local laws relating to medical information. Informed consent of the parent or legal guardian was obtained as required by local law.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"BH: Is an Investigator in the RETRIEVE study and in P1-GM101 Lysogene clinical trial and in other clinical studies supported by Orphazyme\/KemPharm, Azafaros, Sanofi Genzyme, Chiesi, JR Pharmaceuticals, Mallinckrodt. SB: Nothing to disclose. EM: Has received research grants and consultation fees and speakers\u2019 honoraria from Sanofi Genzyme, Amicus, Takeda, Orphazyme, Prevail, Idorsia, Cyclo Therapeutics, Sio and Taysha. RG: Has received research grants, investigator fee, speaker honorarium, support for travel to scientific meetings, or consultation fee from Abeona, Allievex, Amicus, Avrobio, Azafaros, BioMarin, Chiesi, Cyclo, Denali, Idorsia, Inventiva, Janssen, JCR, Novartis, Paradigm, PassageBio, Pfizer, PTC, RegenxBio, Sanofi, Sigilon, Sobi, Takeda, and Ultragenyx. MP: Is an investigator in trials supported by Amicus, Glycomine, Idorsia, Maggie\u2019s Pearl, Orphazyme\/KemPharm and Shire\/Takeda; receives honoraria as Editor-in-Chief of the Journal of Child Neurology (Sage), Editor of JIMD and JIMD Reports (SSIEM), and royalties as a contributor to, and section editor for, UpToDate (Wolters-Kluwer); owns stock in IntraBio. MG: Has received consulting fees from Sanofi Genzyme, and is an investigator for industrial trials from Horizon, Idorsia, Kaleido, Mallinckrodt, and Orphazyme A\/S. PC: Employee of Idorsia Pharmaceuticals Ltd. LT: Employee of Idorsia Pharmaceuticals Ltd. at the time the work was performed. BS: Employee of Idorsia Pharmaceuticals Ltd. MR: Has received consulting fees from Sanofi Genzyme, and travel expenses and congress fees from Amicus.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"459"}}