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

Authors :
Marelli, Cecilia
Lavigne, Christian
Stepien, Karolina M.
Janssen, Mirian C. H.
Feillet, Francois
Kožich, Viktor
Jesina, Pavel
Schule, Rebecca
Kessler, Christoph
Redonnet‐Vernhet, Isabelle
Regnier, Adeline
Burda, Patricie
Baumgartner, Matthias
Benoist, Jean‐Francois
Huemer, Martina
Mochel, Fanny
Source :
Journal of Inherited Metabolic Disease; May2021, Vol. 44 Issue 3, p777-786, 10p
Publication Year :
2021

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01418955
Volume :
44
Issue :
3
Database :
Complementary Index
Journal :
Journal of Inherited Metabolic Disease
Publication Type :
Academic Journal
Accession number :
150237020
Full Text :
https://doi.org/10.1002/jimd.12323