Clinical chemistry and molecular biology of homocysteine metabolism: an update.
OBJECTIVE
To summarize recent developments in our understanding of homocysteine as a clinically relevant and independent predictor of vaso-occlusive disease (including atherosclerosis and thromboembolism), as an early indicator of folate or cobalamin deficiency, and as a key factor in the pathogenesis of neural tube defects.


RESULTS
To determine total homocysteine, plasma or serum must be separated shortly after collection and subjected to chemical reduction. Reference intervals should take into account the prevalence of physiological hyperhomocystinemia. A common cause of hyperhomocystinemia is a genetic predisposition caused by a polymorphic substitution in the methylenetetrahydrofolate reductase (MTHFR) gene, which can be readily detected by molecular means.


CONCLUSIONS
Determination of homocysteine and MTHFR testing should be limited to laboratories with relevant expertise and ability to maintain the high degree of precision required for reliable interpretation. Assays should be offered in selected cases with clinical features or laboratory findings suggestive of hyperhomocystinemia, since treatment is simple and may be highly effective.
Miner
S E
SE
Department of Medicine, University of Toronto, Ontario, Canada.
Evrovski
J
J
Cole
D E
DE
D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood* / Q000235:genetics; D006712:Homocystinuria / Q000235:genetics; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008954:Models, Biological; D009436:Neural Tube Defects / Q000097:blood; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D017410:Practice Guidelines as Topic; D051437:Renal Insufficiency / Q000097:blood; D014652:Vascular Diseases / Q000097:blood / Q000235:genetics; D014804:Vitamin B Deficiency / Q000097:blood
D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)