title: Methylenetetrahydrofolate reductase (MR) deficiency: thermolability of residual MR activity, methionine synthase activity, and methylcobalamin levels in cultured fibroblasts.
abstract: Methylenetetrahydrofolate reductase (MR) deficiency is the most common inborn error of folate metabolism with more than two dozen patients described. The phenotypic spectrum ranges from severe neurological deterioration and early death to asymptomatic adults. Some patients with a severe deficiency of MR have been shown to have thermolabile reductase at 55 degrees C. Since methyltetrahydrofolate, the product of MR, is a methyl donor for methylcobalamin (MeCbl), the cofactor for methionine synthase (MS), we have looked at MeCbl accumulation and MS activity in fibroblasts from 15 patients with MR deficiency. Thermolabile MR was most often but not always seen in later onset disease. MeCbl levels were often lowest in the patients with early onset disease. All but two patients had levels of methionine synthase within the control range.
authors.affiliation: Hess B. and Diane Finestone Laboratory, Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: D S
authors.initials: DS
authors.lastname: Rosenblatt
authors.forename: H
authors.initials: H
authors.lastname: Lue-Shing
authors.forename: A
authors.initials: A
authors.lastname: Arzoumanian
authors.forename: L
authors.initials: L
authors.lastname: Low-Nang
authors.forename: N
authors.initials: N
authors.lastname: Matiaszuk
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000032:analysis*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000032:analysis / Q000172:deficiency*; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: C019476:mecobalamin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12