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Clinical and molecular characterization of adult patients with late-onset MTHFR deficiency

dc.rights.licenseopenen_US
dc.contributor.authorMARELLI, Cecilia
dc.contributor.authorLAVIGNE, Christian
dc.contributor.authorSTEPIEN, Karolina M.
dc.contributor.authorJANSSEN, Mirian C. H.
dc.contributor.authorFEILLET, Francois
dc.contributor.authorKOZICH, Viktor
dc.contributor.authorJESINA, Pavel
dc.contributor.authorSCHULE, Rebecca
dc.contributor.authorKESSLER, Christoph
hal.structure.identifierLaboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]
dc.contributor.authorREDONNET VERNHET, Isabelle
dc.contributor.authorREGNIER, Adeline
dc.contributor.authorBURDA, Patricie
dc.contributor.authorBAUMGARTNER, Matthias
dc.contributor.authorBENOIST, Jean-Francois
dc.contributor.authorHUEMER, Martina
dc.contributor.authorMOCHEL, Fanny
dc.contributor.authorTHE E-HOD, Consortium
dc.date.accessioned2021-10-26T14:30:20Z
dc.date.available2021-10-26T14:30:20Z
dc.date.issued2021-05
dc.identifier.issn0141-8955 (print) 1573-2665 (online)en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/116613
dc.description.abstractEn5,10-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.isoENen_US
dc.subject.enAdult
dc.subject.enInherited metabolic disease
dc.subject.enLate-onset
dc.subject.enMTHFR deficiency
dc.subject.enNeurology
dc.title.enClinical and molecular characterization of adult patients with late-onset MTHFR deficiency
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/jimd.12323en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed33089527en_US
bordeaux.journalJournal of Inherited Metabolic Diseaseen_US
bordeaux.page777-786en_US
bordeaux.volume44en_US
bordeaux.hal.laboratoriesMaladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03404485
hal.version1
hal.date.transferred2021-10-26T14:30:26Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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