Clinical Information

Homocysteine is an intermediary in the sulfur-amino acid metabolism pathways, linking the methionine cycle to the folate cycle. Inborn errors of metabolism that lead to homocysteinemia or homocysteinuria include cystathionine beta-synthase deficiency (homocystinuria) and various defects of methionine re-methylation. Genetic defects in vitamin cofactors (vitamin B6, B12, and folate) and nutritional deficiency of B12 and folate also lead to abnormal homocysteine accumulation.

Homocysteine concentration is an indicator of acquired folate or cobalamin deficiency, and is a contributing factor in the pathogenesis of neural tube defects. Homocysteine also was thought to be an independent predictor of cardiovascular disease (atherosclerosis, heart disease, thromboembolism), as early observational studies prior to 2000 linked homocysteine to cardiovascular risk and morbidity and mortality. However, following FDA-mandated folic acid supplementation in 1998, homocysteine concentrations decreased by approximately 10% without a similar change in cardiovascular or ischemic events. Currently, the use of homocysteine for assessment of cardiovascular risk is uncertain and controversial. Based on several meta-analyses, at present, homocysteine may be regarded as a weak risk factor for coronary heart disease, and there is a lack of direct causal relationship between hyperhomocysteinemia and cardiovascular disease. It is most likely an indicator of poor lifestyle and diet.

This test should be used in conjunction with plasma amino acids and urine organic acids to aid in the biochemical screening for primary and secondary disorders of methionine metabolism.