Journal Article

DZNE-2021-00116

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Clinical and molecular characterization of adult patients with late-onset MTHFR deficiency.

Marelli, C. ; Lavigne, C. ; Stepien, K. M. ; Janssen, M. C. H. ; Feillet, F. ; Kožich, V. ; Jesina, P. ; Schule, R.DZNE* ; Kessler, C.DZNE* ; Redonnet-Vernhet, I. ; Regnier, A. ; Burda, P. ; Baumgartner, M. ; Benoist, J.-F. ; Huemer, M. ; Mochel, F. ; Consortium, E.-H. (Collaboration Author)

2021

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Please use a persistent id in citations: doi:10.1002/jimd.12323

Abstract: 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 μmol/L, range 69-266, to 90 μmol/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.

Keyword(s): Adolescent (MeSH) ; Adult (MeSH) ; Age of Onset (MeSH) ; Child (MeSH) ; Delayed Diagnosis (MeSH) ; Epilepsy: diagnosis (MeSH) ; Epilepsy: pathology (MeSH) ; Female (MeSH) ; Homocystinuria: diagnosis (MeSH) ; Homocystinuria: pathology (MeSH) ; Humans (MeSH) ; Intellectual Disability: diagnosis (MeSH) ; Intellectual Disability: pathology (MeSH) ; Male (MeSH) ; Methylenetetrahydrofolate Reductase (NADPH2): deficiency (MeSH) ; Middle Aged (MeSH) ; Muscle Spasticity: diagnosis (MeSH) ; Muscle Spasticity: pathology (MeSH) ; Psychotic Disorders: diagnosis (MeSH) ; Psychotic Disorders: pathology (MeSH) ; Retrospective Studies (MeSH) ; Seizures: diagnosis (MeSH) ; Seizures: pathology (MeSH) ; Young Adult (MeSH) ; MTHFR deficiency ; adult ; inherited metabolic disease ; late-onset ; neurology

Note: ISSN 1573-2665 not unique: **3 hits**.

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Contributing Institute(s):

1. Functional Neurogeriatrics (AG Maetzler)
2. Tübingen common (Tübingen common)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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