Genetic basis of hyperhomocysteinemia.

Homocysteine is a sulfur-containing, nonproteinogenic amino acid biosynthesized from methionine which has a key place in common between the folate cycle and the activated methyl cycle. Homocysteine export into the extracellular medium reflects an imbalance between homocysteine production and metabolism (1). Hyperhomocysteinemia has been associated with folate or cobalamine deficiencies, and also with pregnancy complications, neural tube defects, mental disorders, cognitive impairment in the elderly, psoriasis, and some tumors (2). Furthermore, moderately raised concentrations of total homocysteine have been associated with an increased risk of cardiovascular disease (3,4). There are many genetic causes of elevated homocysteine levels. Enzymatic defects and variants have been associated with methylene tetrahydrofolate reductase, methionine synthase, and cystathionine b-synthase, to name only the most relevant. In the present minireview, the main genetic defects associated with increased levels of homocysteine are described.