Thermolabile methylenetetrahydrofolate reductase

Thermolabile methylenetetrahydrofolate reductase (MTHFR) is a homozygous genetic defect that is defined by its in vitro heat sensitivity. Similar to heterozygotes for severe MTHFR deficiency, Specific enzyme activity of thermolabile MTHFR is 50% of the normal mean. Population analysis of the inheritance pattern follows an autosomal recessive trait, and thermolabile MTHFR is the most common homozygous genetic defect. Molecular analysis shows a homozygous C to T transition at the 677th base of cDNA in the majority of thermolabile MTHFR. Genetic compounds of the 677 mutation and severe mutations are also identified as thermolabile MTHFR. There is a positive correlation between thermolabile MTHFR and the development of vascular disease. Thermolabile MTHFR causes hyperhomocysteinemia alone or in combination with other genetic or nongenetic factors. Compared with a single thermolabile mutation, the combination of two defects produces more striking hyperhomocysteinemia. A higher prevalence of thermolabile MTHFR in hyperhomocysteinemic patients with vascular disease than in nonclassified patients suggests a potential association of hyperhomocysteinemia with the development of vascular disease. Interrelationships between thermolabile MTHFR, hyperhomocysteinemia, and the development of vascular disease have yet to be thoroughly elucidated. The investigation of nonallelic heterozygotes with other defects, such as cystathionine beta-synthase (CBS), methionine synthase (MHMT), and betaine homocysteine methyltransferase (BHMT), which are enzymes for the synthesis of cofactors, may be import but in establishing this relationship.