Last update:
10-Sep-2004

Hyperhomocysteinemia has been recognized during the last decades as an independent risk factor for cardiovascular disease and thromboembolic episodes. Homocysteine is an amino acid derived from methionine in food, and its metabolism follows two main routes: the remethylation pathway, with the action of the enzymes methionine-synthase (MS) and N₅,N₁₀-methylenotetrahydrofolic reductase (MTHFR) and the contribution of folic acid and vitamin B₁₂, and the transsulfuration pathway with cystathionine-β-synthase (CBS) as the main enzyme with the contribution of vitamin B₆. The most reliable methods for the determination of homocysteine are chromatographic (HPLC) and immunoenzymatic (ELISA). Normal levels are 5-15 μmol/L and hyperhomocysteinemia is graded as mild (15-30 μmol/L), moderate (30-100 μmol/L) and severe (above 100 μmol/L). The methionine loading test contributes to the diagnosis of borderline disturbances even though its usefulness is questioned by some. The causes of hyperhomocysteinemia are dietary, genetic or other. Defects of CBS or MTHFR are the cause of severe or moderate disease in their homozygous and heterozygous forms respectively, whereas the presence of the thermolabile variant of MTHFR is usually associated with the moderate form. An increase in homocysteine, regardless of the underlying cause, has been associated with cardiovascular disease and thromboembolic episodes, the association being supported by several clinical studies, retrospective, prospective and other. The pathogenesis of the cardiovascular disease lies in endothelial dysfunction and its prothrombotic role, due to the toxic effects of homocysteine and the products of its oxidation. The management of hyperhomocysteinemia, depending on the severity of the disorder, is by increased intake of food rich in vitamins, especially folic acid, enrichment of food (e.g. breakfast cereals) with folic acid, or treatment with specific vitamins, i.e. folic acid, vitamin B₁₂, vitamin B₆, either singly or in combination.

Key words: Homocysteine, Hyperhomocysteinemia, Thrombosis.