Browse by author
Lookup NU author(s): Professor Patrick Chinnery
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Background Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn defect disturbing the remethylation of homocysteine to methionine (<200 reported cases). This retrospective study evaluates clinical, biochemical genetic and in vitro enzymatic data in a cohort of 33 patients.Methods Clinical, biochemical and treatment data was obtained from physicians by using a questionnaire. MTHFR activity was measured in primary fibroblasts; genomic DNA was extracted from cultured fibroblasts.Results Thirty-three patients (mean age at follow-up 11.4 years; four deceased; median age at first presentation 5 weeks; 17 females) were included. Patients with very low (<1.5 %) mean control values of enzyme activity (n=14) presented earlier and with a pattern of feeding problems, encephalopathy, muscular hypotonia, neurocognitive impairment, apnoea, hydrocephalus, microcephaly and epilepsy. Patients with higher (>1.7-34.8 %) residual enzyme activity had mainly psychiatric symptoms, mental retardation, myelopathy, ataxia and spasticity. Treatment with various combinations of betaine, methionine, folate and cobalamin improved the biochemical and clinical phenotype. During the disease course, patients with very low enzyme activity showed a progression of feeding problems, neurological symptoms, mental retardation, and psychiatric disease while in patients with higher residual enzyme activity, myelopathy, ataxia and spasticity increased. All other symptoms remained stable or improved in both groups upon treatment as did brain imaging in some cases. No clear genotype-phenotype correlation was obvious.Discussion MTHFR deficiency is a severe disease primarily affecting the central nervous system. Age at presentation and clinical pattern are correlated with residual enzyme activity. Treatment alleviates biochemical abnormalities and clinical symptoms partially.
Author(s): Huemer M, Mulder-Bleile R, Burda P, Froese DS, Suormala T, Ben Zeev B, Chinnery PF, Dionisi-Vici C, Dobbelaere D, Gökcay G, Demirkol M, Häberle J, Lossos A, Mengel E, Morris AA, Niezen-Koning KE, Plecko B, Parini R, Rokicki D, Schiff M, Schimmel M, Sewell AC, Sperl W, Spiekerkoetter U, Steinmann B, Taddeucci G, Trejo-Gabriel-Galán JM, Trefz F, Tsuji M, Vilaseca MA, von Kleist-Retzow JC, Walker V, Zeman J, Baumgartner MR, Fowler B
Publication type: Article
Publication status: Published
Journal: Journal of Inherited Metabolic Disease
Year: 2016
Volume: 39
Issue: 1
Pages: 115-124
Print publication date: 01/01/2016
Online publication date: 30/05/2015
Acceptance date: 29/04/2015
ISSN (print): 0141-8955
ISSN (electronic): 1573-2665
Publisher: Springer Netherlands
URL: http://dx.doi.org/10.1007/s10545-015-9860-6
DOI: 10.1007/s10545-015-9860-6
Altmetrics provided by Altmetric
