Study type: Blood collected in a gold-, red-, or red/gray-top tube if methylmalonic acid and homocysteine are to be measured together; related body system: Circulatory system. Alternatively, a lavender-top [EDTA] tube may be acceptable for the homocysteine measurement. The laboratory should be consulted before specimen collection because specimen type may be method dependent. Care must be taken to use the same type of collection container if serial measurements are to be taken.

Homocysteine is an amino acid formed from methionine. Normally, homocysteine is rapidly remetabolized in a biochemical pathway that requires vitamin B₁₂ and folate, preventing the buildup of homocysteine in the blood. Excess levels damage the endothelial lining of blood vessels; change coagulation factor levels, increasing the risk of blood clot formation and stroke; prevent smaller arteries from dilating, increasing the risk of plaque formation; cause platelet aggregation; and cause smooth muscle cells lining the arterial wall to multiply, promoting atherosclerosis. For additional information regarding screening guidelines for atherosclerotic cardiovascular disease (ASCVD), refer to the study titled “Cholesterol, Total and Fractions.”

Approximately one-third of patients with hyperhomocystinuria have normal fasting levels. Patients with a heterozygous biochemical enzyme defect in cystathionine B synthase or with a nutritional deficiency in vitamin B₆ can be identified through the administration of a methionine challenge or loading test. Specimens are collected while fasting and 2 hr later. An increase in homocysteine after 2 hr is indicative of hyperhomocystinuria. In patients with vitamin B₁₂ deficiency, elevated levels of methylmalonic acid and homocysteine develop fairly early in the course of the disease. Unlike vitamin B₁₂ levels, homocysteine levels will remain elevated for at least 24 hr after the start of vitamin therapy. This may be useful if vitamin therapy is inadvertently begun before specimen collection. Patients with folate deficiency, for the most part, will only develop elevated homocysteine levels. A methylmalonic acid level can differentiate between vitamin B₁₂ and folate deficiency, since it is increased in vitamin B₁₂ deficiency but not in folate deficiency. Hyperhomocysteinemia due to folate deficiency in pregnant women is believed to increase the risk of neural tube defects. Elevated levels of homocysteine are thought to chemically damage the exposed neural tissue of the developing fetus.