Mutated 5,10-methylenetetrahydrofolate reductase and moderate hyperhomocysteinaemia.
Moderate hyperhomocysteinaemia (MHH) is a risk factor for arteriosclerosis and thrombosis. About 10%-20% of the normal population have homocysteine levels contributing to an increased risk for arterial and venous disease. Main regulating enzymes of homocysteine metabolism are cystathionine beta-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR). Heterozygosity for CBS deficiency is most likely not an important cause for MHH in vascular disease. A recently discovered cause of MHH is reduced MTHFR activity due to a homozygous C677T mutation in the coding region of MTHFR. This mutation has been related to an increased risk for cardiovascular disease, although a number of studies are not confirmative. The elevated homocysteine levels due to this mutation can be normalized by administration of vitamins involved in homocysteine metabolism, in particular folate.
Blom
H J
HJ
Department of Paediatrics University Hospital Nijmegen, The Netherlands. h.blom@ckslkn.azn.nl
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications*; D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications / Q000201:enzymology; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D009436:Neural Tube Defects / Q000150:complications / Q000201:enzymology; D010088:Oxidoreductases / Q000235:genetics*; D013927:Thrombosis / Q000097:blood* / Q000150:complications / Q000201:enzymology
D006710:Homocysteine; D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2)