Clinical and molecular characterization of adult patients with late-onset MTHFR deficiency
| dc.rights.license | open | en_US |
| dc.contributor.author | MARELLI, Cecilia | |
| dc.contributor.author | LAVIGNE, Christian | |
| dc.contributor.author | STEPIEN, Karolina M. | |
| dc.contributor.author | JANSSEN, Mirian C. H. | |
| dc.contributor.author | FEILLET, Francois | |
| dc.contributor.author | KOZICH, Viktor | |
| dc.contributor.author | JESINA, Pavel | |
| dc.contributor.author | SCHULE, Rebecca | |
| dc.contributor.author | KESSLER, Christoph | |
| hal.structure.identifier | Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM] | |
| dc.contributor.author | REDONNET VERNHET, Isabelle | |
| dc.contributor.author | REGNIER, Adeline | |
| dc.contributor.author | BURDA, Patricie | |
| dc.contributor.author | BAUMGARTNER, Matthias | |
| dc.contributor.author | BENOIST, Jean-Francois | |
| dc.contributor.author | HUEMER, Martina | |
| dc.contributor.author | MOCHEL, Fanny | |
| dc.contributor.author | THE E-HOD, Consortium | |
| dc.date.accessioned | 2021-10-26T14:30:20Z | |
| dc.date.available | 2021-10-26T14:30:20Z | |
| dc.date.issued | 2021-05 | |
| dc.identifier.issn | 0141-8955 (print) 1573-2665 (online) | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/116613 | |
| dc.description.abstractEn | 5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency usually presents as a severe neonatal disease. This study aimed to characterize natural history, biological and molecular data, and response to treatment of patients with late-onset MTHFR deficiency. The patients were identified through the European Network and Registry for Homocystinuria and Methylation Defects and the Adult group of the French Society for Inherited Metabolic Diseases; data were retrospectively colleted. To identify juvenile to adult-onset forms of the disease, we included patients with a diagnosis established after the age of 10 years. We included 14 patients (median age at diagnosis: 32 years; range: 11-54). At onset (median age: 20 years; range 9-38), they presented with walking difficulties (n = 8), cognitive decline (n = 3) and/or seizures (n = 3), sometimes associated with mild mental retardation (n = 6). During the disease course, symptoms were almost exclusively neurological with cognitive dysfunction (93%), gait disorders (86%), epilepsy (71%), psychiatric symptoms (57%), polyneuropathy (43%), and visual deficit (43%). Mean diagnostic delay was 14 years. Vascular events were observed in 28% and obesity in 36% of the patients. One patient remained asymptomatic at the age of 55 years. Upon treatment, median total homocysteine decreased (from 183 ?mol/L, range 69-266, to 90 ?mol/L, range 20-142) and symptoms improved (n = 9) or stabilized (n = 4). Missense pathogenic variants in the C-terminal regulatory domain of the protein were over-represented compared to early-onset cases. Residual MTHFR enzymatic activity in skin fibroblasts (n = 4) was rather high (17%-58%). This series of patients with late-onset MTHFR deficiency underlines the still unmet need of a prompt diagnosis of this treatable disease. | |
| dc.language.iso | EN | en_US |
| dc.subject.en | Adult | |
| dc.subject.en | Inherited metabolic disease | |
| dc.subject.en | Late-onset | |
| dc.subject.en | MTHFR deficiency | |
| dc.subject.en | Neurology | |
| dc.title.en | Clinical and molecular characterization of adult patients with late-onset MTHFR deficiency | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1002/jimd.12323 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| dc.identifier.pubmed | 33089527 | en_US |
| bordeaux.journal | Journal of Inherited Metabolic Disease | en_US |
| bordeaux.page | 777-786 | en_US |
| bordeaux.volume | 44 | en_US |
| bordeaux.hal.laboratories | Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211 | en_US |
| bordeaux.issue | 3 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | INSERM | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.identifier | hal-03404485 | |
| hal.version | 1 | |
| hal.date.transferred | 2021-10-26T14:30:26Z | |
| hal.export | true | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Inherited%20Metabolic%20Disease&rft.date=2021-05&rft.volume=44&rft.issue=3&rft.spage=777-786&rft.epage=777-786&rft.eissn=0141-8955%20(print)%201573-2665%20(online)&rft.issn=0141-8955%20(print)%201573-2665%20(online)&rft.au=MARELLI,%20Cecilia&LAVIGNE,%20Christian&STEPIEN,%20Karolina%20M.&JANSSEN,%20Mirian%20C.%20H.&FEILLET,%20Francois&rft.genre=article |
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