Increased plasma lev- els of homocysteine are often a consequence of reduced enzy- matic 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, respec- tively, 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).759 Hyperhomocysteinemia also is caused by nutritional deficiencies of pyridoxine (vita- ), a cofactor of cystathionine -synthase, and of folic acid and cobalamin (vitamin B12 ), cofactors of MTHFR.760 Decreased renal clearance of homocysteine in patients with chronic renal failure may contribute to hyperhomocysteinemia. 