{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:11:45Z","timestamp":1792026705421,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>GM2 gangliosidoses are lysosomal diseases due to biallelic mutations in the <jats:italic>HEXA<\/jats:italic> (Tay\u2013Sachs disease [TS]) or <jats:italic>HEXB<\/jats:italic> (Sandhoff disease [SD]) genes, with subsequent low hexosaminidase(s) activity. Most patients have childhood onset, but some experience the first symptoms during adolescence\/adulthood. This study aims to clarify the natural history of adult patients with GM2 gangliosidosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively described 12 patients from a French cohort and 45 patients from the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed 4 typical presentations: (1) lower motoneuron disorder responsible for proximal lower limb weakness that subsequently expanded to the upper limbs, (2) cerebellar ataxia, (3) psychosis and\/or severe mood disorder (only in the TS patients), and (4) a complex phenotype mixing the above 3 manifestations. The psoas was the first and most affected muscle in the lower limbs, whereas the triceps and interosseous were predominantly involved in the upper limbs. A longitudinal study of compound motor action potentials showed a progressive decrease in all nerves, with different kinetics. Sensory potentials were sometimes abnormally low, mainly in the SD patients. The main brain magnetic resonance imaging feature was cerebellar atrophy, even in patients without cerebellar symptoms. The prognosis was mainly related to gait disorder, as we showed that beyond 20\u2009years of disease evolution, half of the patients were wheelchair users.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Improved knowledge of GM2 gangliosidosis in adults will help clinicians achieve correct diagnoses and better inform patients on the evolution and prognosis. It may also contribute to defining proper outcome measures when testing emerging therapies. <jats:bold>ANN NEUROL 2020;87:609\u2013617<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25689","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T10:42:04Z","timestamp":1580294524000},"page":"609-617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Natural History of Adult Patients with GM2 Gangliosidosis"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4898-709X","authenticated-orcid":false,"given":"Marion","family":"Masingue","sequence":"first","affiliation":[{"name":"Reference Center for Neuromuscular Disorders Nord\/Est\/\u00cele\u2010de\u2010France Institute of Myology, Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital Group (Assistance publique H\u00f4pitaux de Paris (AP\u2010HP))  Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Dufour","sequence":"additional","affiliation":[{"name":"Department of Neurology Reference Center for Lysosomal Diseases, Neuro\u2010Genetic and Metabolism Unit, Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital Group (Assistance publique H\u00f4pitaux de Paris (AP\u2010HP))  Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timoth\u00e9e","family":"Lenglet","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital Group (Assistance publique H\u00f4pitaux de Paris (AP\u2010HP))  Paris"},{"name":"Department of Neurology Reference Center for ALS Rare Disease, Piti\u00e9\u2010Salp\u00eatri\u00e8re University Hospital Group (Assistance publique H\u00f4pitaux de Paris (AP\u2010HP))  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