Homocysteine, Total, Plasma
An aid for screening patients suspected of having an inherited disorder of methionine metabolism including:
-Cystathionine beta-synthase deficiency (homocystinuria)
-Methylenetetrahydrofolate reductase deficiency (MTHFR) and its thermolabile variants:
-Methionine synthase deficiency
-Cobalamin (Cbl) metabolism:
-Combined methyl-Cbl and adenosyl-Cbl deficiencies: Cbl C2, Cbl D2, and Cbl F3 deficiencies
-Methyl-Cbl specific deficiencies: Cbl D-Var1, Cbl E, and Cbl G deficiencies
-Transcobalamin II deficiency:
-Adenosylhomocysteinase (AHCY) deficiency
-Glycine N-methyltransferase (GNMT) deficiency
-Methionine adenosyltransferase (MAT) I/III deficiency
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 homocystinuria include cystathionine beta-synthase deficiency (homocystinuria) and various defects of methionine remethylation. 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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Adults: < or =13 mcmol/L
Reference values apply to fasting specimens only.
Homocysteine concentrations >13 mcmol/L are considered abnormal in patients evaluated for suspected nutritional deficiencies (B12, folate) and inborn errors of metabolism. Measurement of methylmalonic acid (MMA) distinguishes between B12 (cobalamin) and folate deficiencies, as MMA is only elevated in B12 deficiency. Response to dietary treatment can be evaluated by monitoring plasma homocysteine concentrations over time.
Homocysteine concentrations < or =10 mcmol/L are desirable when utilized for cardiovascular risk.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A fasting specimen is recommended; however, nonfasting homocysteine concentrations produce slightly higher, but likely clinically insignificant changes.
Other factors that may influence and increase plasma homocysteine include:
-Poor diet/cofactor deficiencies
-Chronic kidney disease/renal disease
Medications that may increase homocysteine concentrations include:
Vitamin B6 antagonist
Inactivation of methionine synthase
Interference with folate metabolism
Interference with folate metabolism
Estrogen-induced vitamin B6 deficiency
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Mudd SH, Levy HL, Kraus JP: Disorders of transsulfuration. In The Metabolic and Molecular Basis of Inherited Disease. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw Hill Book Company, 2001, pp 2007-2056
2. Myers GL, Christenson RH, Cushman M, et al: National Academy of Clinical Biochemistry Laboratory Medicine Practice guidelines: emerging biomarkers for primary prevention of cardiovascular disease. Clin Chem, 2009;55(2):51-57
3. Refsum H, Smith AD, Ueland PM, et al: Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004 January;50:3-32
4. Turgeon CT, Magera MJ, Cuthbert CD, et al: Determination of total homocysteine, methylmalonic acid, and 2-methylcitric acid in dried blood spots by tandem mass spectrometry. Clin Chem 2010 November;56:1686-1695