Order Code
4288
Preferred Specimen
A 1 mL serum sample is required. Store the sample on ice until separation. Allow the SST tube to clot in an upright position for at least 30 minutes, then centrifuge the sample within 1 hour of collection. Refrigerate the serum. Patients taking methotrexate, carbamazepine, phenytoin, nitrous oxide, anticonvulsants, or 6-azuridine triacetate may exhibit elevated homocysteine levels due to interference with homocysteine metabolism.
ContainerType
Serum separator tube
Alternate Specimen Requirements
A 1 mL serum sample from a plain red top tube is acceptable. Keep the sample on ice until separation. Allow the sample to clot in an upright position for at least 60 minutes, then centrifuge and transfer the serum to a plastic transport tube within 2 hours of collection. Ensure the tube is clearly labeled as serum from a plain red top tube. Refrigerate the serum. As with the preferred specimen, patients on methotrexate, carbamazepine, phenytoin, nitrous oxide, anticonvulsants, or 6-azuridine triacetate may have elevated homocysteine levels due to interference with its metabolism.
Minimum Volume
0.5 mL serum
Transport Temperature
Refrigerated
Expected Turnaround Time
2 days
Specimen Stability
4 days room temperature; 1 week refrigerated; 1 month frozen
Methodology
Roche COBAS enzymatic method
Rejection Criteria
- Hemolysis
Overview
Homocysteine (Hyc) is a sulfur-containing amino acid produced during the conversion of methionine (an essential amino acid) to cysteine. The subsequent metabolism of homocysteine depends on several B vitamins. Homocysteine levels tend to rise when there are deficiencies in vitamin B12 and folate or when there are inherited disorders affecting methionine metabolism.
Elevated homocysteine levels are linked to vitamin B12 and folate deficiencies, as well as conditions such as genetic homocysteinemia, Alzheimer’s disease, dementia, kidney disease, eye disorders, and diabetes. Epidemiological research has shown an association between high homocysteine levels and cardiovascular conditions such as coronary artery disease, peripheral artery disease, and stroke. Homocysteine testing can be useful for risk assessment in patients with a strong personal or family history of cardiovascular disease but no established risk factors like smoking, high cholesterol, high blood pressure, or diabetes.
Clinical Significance
- Evaluation of B12 and folate deficiency
- Diagnose homocystinuria (rare autosomal recessive inborn error of cobalamin [B12] and folate metabolism)
- Monitor replacement folic acid therapy
- Potential (though not widely endorsed) uses:
- Assess risk of vascular disease (myocardial infarction or stroke) despite a low-risk profile
- Part of evaluation of thromboembolic disease (to help detect presence of abnormal MTHFR gene resulting in elevated homocysteine levels)
Additional Information
Homocysteine can degrade and interfere with the formation of key structural components of arteries, including collagen, elastin, and proteoglycans. This leads to damage of the arterial inner lining, contributing to narrowing where platelets may accumulate and form clots.
Interpretative Information
Elevated levels:
- Folate deficiency
- Vitamin B12 deficiency
- Familial hyperhomocysteinemia
- Renal insufficiency
- Hypothyroidism
- Certain medications (eg, methotrexate, carbamazepine, phenytoin, steroids, cyclosporine, levodopa, methotrexate)
- MTHFR (methylenetetrahydrofolate reductase) genetic mutations
- Certain malignancies (eg, breast, ovarian, and pancreatic cancer)
Decreased levels:
- Uncommon and not felt to be clinically significant
- May be due to daily vitamin intake such as daily folic acid, vitamin B12, or niacin
Limitations
False elevation:
- Treatment with s-adenosylmethionine (SAM) (OTC dietary supplement)
- Human antimouse antibodies (HAMA) may interfere with measurement
- May occur if serum is not separated from the cells at the time of collection
References
American Heart Association. Homocysteine, Folic Acid and Cardiovascular Disease. 2014. http://www.heart.org/HEARTORG/GettingHealthy/NutritionCenter/Homocysteine-Folic-Acid-and-Cardiovascular-Disease_UCM_305997_Article.jsp. Accessed April 10, 2014.
Bjørke Monsen Al, Ueland PM. Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence. Am J Clin Nutr. 2003;78(1):7-21.12816766
Horton GL. Homocysteine: clinical significance and laboratory measurement. Lab Med. 2006;37(9):551-553. http://www.medscape.com/viewarticle/543938_5. Accessed April 21, 2014.
Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288(16):2015-2022.12387654
Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340(19):1449-1454.1032038
Klee GG. Cobalamin and folate evaluation: measurement of methylmalonic acid and homocysteine vs vitamin B(12) and folate. Clin Chem. 2000;46(8 Pt 2):1277-1283.10926922
Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003;67(5):979-986.12643357
Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346(7):476-483.11844848
Varga EA, Sturm AC, Misita CP, Moll S. Cardiology patient pages. Homocysteine and MTHFR mutations: relation to thrombosis and coronary artery disease. Circulation. 2005;111(19):e289-293.15897349
Vermeulen EG, Stehouwer CD, Twisk JW, van den Berg M, de Jong SC, Mackaay AJ. et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomized, placebo-controlled trial. Lancet. 2000;355(9203):517-522.10683000
Welch GN, Loscalzo J. Homocysteine and atherothrombosis. N Engl J Med. 1998;338(15):1042-1050.9535670
Yetley EA, Pfeiffer CM, Phinney KW, Fazili Z, Lacher DA, Bailey RL, et al. Biomarkers of folate status in NHANES: a roundtable summary. Am J Clin Nutr. 2011;94(1):303S-312S.21593502
Diagnostic Role
Homocysteine is most commonly used as a marker for vitamin B12 and folate deficiency, and is elevated in both conditions. It is commonly ordered in conjunction with methylmalonic acid (MMA) when vitamin B12 levels are in the low-normal range, yet clinical suspicion persists for B12 deficiency. Homocysteine is also ordered to confirm and distinguish vitamin B12 from folic acid deficiency: Both homocysteine and MMA are elevated in B12 deficiency, whereas only homocysteine is elevated in folic acid deficiency.
| Condition | MMA Level | Homocysteine Level |
|---|---|---|
| B12 deficiency | ↑ | ↑ |
| Folate deficiency | Normal | ↑ |
Elevated homocysteine may be one of the earliest manifestations of vitamin B12deficiency, preceding anemia and macrocytosis. It is important to note that homocysteine may be affected by other factors, such as renal failure, folate deficiency, tobacco, and alcohol abuse, and it is less specific than MMA for identifying vitamin B-12 deficiency. Homocysteine levels normalize with vitamin replacement.
Elevated homocysteine levels have been found in cardiovascular disease, where evidence suggests homocysteine may promote atherosclerosis by damaging the inner lining of arteries and promoting blood clots. (AHA, 2014) However, lowering homocysteine levels has not been shown to decrease the risk for atherosclerosis or thrombosis. (Varga, 2005) At present, there are no broadly endorsed recommendations for formal testing of homocysteine levels in cardiovascular evaluations; however, such testing may aid in risk assessment in selected patients where established risk factors (tobacco use, hyperlipidemia, hypertension, diabetes) are absent, yet there remains a strong personal or family history of cardiovascular disease.
Test Setup Days
Monday through Friday PM shift
CPT
83090 Limited Coverage Test For Medicare.
Advance Beneficiary Notice Of Non-Coverage (ABN) Required
If Diagnosis Is Not Covered.
Frequency Limit Test For Medicare.
Advance Beneficiary Notice Of Non-Coverage (ABN) Always
Required For Frequency.
LOINC:13965-9
Reference Range
AGE: <15: <8 UMOL/L
15-65: <12 UMOL/L
>65: <16 UMOL/L
| UNIT CODE | UNIT CODE NAME | ANALYTE | GENDER | AGE | REFERENCE RANGE | Units of Measure |
|---|---|---|---|---|---|---|
| 4288 | HOMOCYSTEINE | HOMO | NOT SPECIFIED | 0Y | <16 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | NOT SPECIFIED | 15Y | <8 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | NOT SPECIFIED | 65Y | <12 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | NOT SPECIFIED | 150Y | <16 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | MALE | 0Y | <16 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | MALE | 15Y | <8 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | MALE | 65Y | <12 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | MALE | 150Y | <16 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | FEMALE | 0Y | <16 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | FEMALE | 15Y | <8 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | FEMALE | 65Y | <12 | UMOL/L |
| 4288 | HOMOCYSTEINE | HOMO | FEMALE | 150Y | <16 | UMOL/L |