What causes increased plasma levels of homocysteine?
Increased plasma levels of homocysteine are often a consequence of reduced enzymatic activity in its metabolic pathways. This may be caused by genetic defects in the enzymes involved in homocysteine metabolism such as deficiencies of cystathionine-synthase and methylenetetrahydrofolate reductase (MTHFR), involved in the transsulfuration and remethylation pathways, respectively, or by a thermolabile variant of MTHFR that results from a point mutation in which cytosine is replaced by thymidine at position 677 (MTHFR C677T). Hyperhomocysteinemia also is caused by nutritional deficiencies of pyridoxine (vitamin B6), a cofactor of cystathionine-synthase, and of folic acid and cobalamin (vitamin B12), cofactors of MTHFR. Decreased renal clearance of homocysteine in patients with chronic renal failure may contribute to hyperhomocysteinemia.