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HelpTest ID HCYSS Homocysteine, Total, Serum
Useful For
An aid for screening patients suspected of having an inherited disorder of methionine metabolism including:
-Cystathionine beta-synthase deficiency (homocystinuria)
-Methylenetetrahydrofolate reductase deficiency 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 deficiency
-Glycine N-methyltransferase deficiency
-Methionine adenosyltransferase I/III deficiency
Screening and monitoring patients suspected of, or confirmed with, an inherited disorder of methionine metabolism
Evaluating individuals with suspected deficiency of vitamin B12 or folate
Disease States
- Homocystinuria
Reporting Name
Homocysteine, Total, SSpecimen Type
SerumNecessary Information
Patient's age and sex are required.
Specimen Required
Container/Tube:
Preferred: Serum gel
Acceptable: Red top
Specimen Volume: 1 mL
Collection Instructions: Centrifuge and aliquot serum into plastic vial within 4 hours of collection.
Specimen Minimum Volume
0.3 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 28 days | |
| Frozen | 309 days | ||
| Ambient | 28 days |
Reject Due To
| Gross hemolysis | OK |
| Gross lipemia | OK |
| Gross icterus | OK |
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 homocystinuria include cystathionine beta-synthase deficiency (homocystinuria) and various defects of methionine remethylation. Genetic defects in vitamin cofactors (vitamins B6, B12, and folate) and nutritional deficiency of vitamin 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 was once thought to be an independent predictor of cardiovascular disease (atherosclerosis, heart disease, thromboembolism), as early observational studies prior to the year 2000 linked homocysteine to cardiovascular risk and morbidity and mortality. However, following U.S. Food and Drug Administration 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, quantitative acylcarnitines, methylmalonic acid, and urine organic acids to aid in the biochemical screening for primary and secondary disorders of methionine metabolism.
Reference Values
|
Age |
Total Homocysteine (nmol/mL) |
|
|
Female |
Male |
|
|
0-11 months |
3.1-8.3 |
3.2-9.7 |
|
12-23 months |
3.2-8.3 |
3.3-9.6 |
|
24-35 months |
3.2-8.2 |
3.3-9.6 |
|
3 years |
3.2-8.2 |
3.3-9.6 |
|
4 years |
3.3-8.2 |
3.4-9.5 |
|
5 years |
3.4-8.1 |
3.5-9.4 |
|
6 years |
3.5-8.1 |
3.6-9.4 |
|
7 years |
3.5-8.1 |
3.7-9.4 |
|
8 years |
3.6-8.2 |
3.8-9.3 |
|
9 years |
3.7-8.2 |
3.9-9.4 |
|
10 years |
3.8-8.3 |
4.1-9.4 |
|
11 years |
3.9-8.4 |
4.3-9.4 |
|
12 years |
3.9-8.6 |
4.4-9.5 |
|
13 years |
4.0-8.7 |
4.6-9.6 |
|
14 years |
4.1-8.8 |
4.8-9.7 |
|
15 years |
4.2-8.9 |
5.0-9.8 |
|
16 years |
4.2-9.1 |
5.2-9.9 |
|
17 years |
4.3-9.2 |
5.4-10.0 |
|
18 years |
4.3-9.3 |
5.6-10.1 |
|
19 years |
4.4-9.5 |
5.7-10.3 |
|
20 years |
4.4-9.6 |
5.9-10.5 |
|
21 years |
4.4-9.8 |
6.0-10.6 |
|
22 years |
4.4-9.9 |
6.1-10.8 |
|
23 years |
4.4-10.1 |
6.2-11.0 |
|
24 years |
4.4-10.3 |
6.2-11.1 |
|
25 years |
4.4-10.4 |
6.3-11.3 |
|
26 years |
4.4-10.6 |
6.3-11.4 |
|
27 years |
4.3-10.8 |
6.4-11.6 |
|
28 years |
4.3-11.0 |
6.4-11.7 |
|
29 years |
4.3-11.2 |
6.4-11.8 |
|
30 years |
4.3-11.4 |
6.4-11.9 |
|
31 years |
4.4-11.6 |
6.4-12.1 |
|
32 years |
4.4-11.8 |
6.4-12.2 |
|
33 years |
4.4-11.9 |
6.4-12.3 |
|
34 years |
4.5-12.1 |
6.4-12.4 |
|
35 years |
4.5-12.2 |
6.4-12.6 |
|
36 years |
4.6-12.4 |
6.4-12.8 |
|
37 years |
4.6-12.5 |
6.4-12.9 |
|
38 years |
4.7-12.7 |
6.4-13.1 |
|
39 years |
4.7-12.8 |
6.4-13.2 |
|
40 years |
4.8-13.0 |
6.5-13.4 |
|
41 years |
4.8-13.2 |
6.5-13.5 |
|
42 years |
4.8-13.4 |
6.5-13.7 |
|
43 years |
4.9-13.5 |
6.6-13.9 |
|
44 years |
4.9-13.7 |
6.6-14.0 |
|
45 years |
4.9-13.9 |
6.6-14.2 |
|
46 years |
4.9-14.0 |
6.7-14.4 |
|
47 years |
4.9-14.2 |
6.7-14.5 |
|
48 years |
5.0-14.3 |
6.8-14.7 |
|
49 years |
5.0-14.4 |
6.8-14.9 |
|
50 years |
5.0-14.5 |
6.8-15.0 |
|
51 years |
5.1-14.6 |
6.8-15.2 |
|
52 years |
5.1-14.7 |
6.9-15.4 |
|
53 years |
5.1-14.8 |
6.9-15.5 |
|
54 years |
5.2-14.9 |
6.9-15.6 |
|
55 years |
5.2-15.0 |
6.9-15.7 |
|
56 years |
5.3-15.0 |
6.9-15.8 |
|
57 years |
5.3-15.1 |
6.9-15.9 |
|
58 years |
5.3-15.2 |
6.9-16.0 |
|
59 years |
5.4-15.2 |
6.9-16.0 |
|
60 years |
5.4-15.3 |
6.9-16.1 |
|
61 years |
5.4-15.4 |
7.0-16.2 |
|
62 years |
5.5-15.4 |
7.0-16.2 |
|
63 years |
5.5-15.5 |
7.0-16.3 |
|
64 years |
5.6-15.5 |
7.1-16.3 |
|
65 years |
5.6-15.6 |
7.1-16.3 |
|
66 years |
5.7-15.6 |
7.1-16.3 |
|
67 years |
5.7-15.7 |
7.2-16.3 |
|
68 years |
5.8-15.7 |
7.2-16.3 |
|
69 years |
5.9-15.7 |
7.2-16.3 |
|
70 years |
6.0-15.8 |
7.3-16.3 |
|
71 years |
6.1-15.8 |
7.3-16.3 |
|
72 years |
6.2-15.8 |
7.3-16.3 |
|
73 years |
6.3-15.9 |
7.3-16.3 |
|
74 years |
6.4-15.9 |
7.3-16.3 |
|
75 years |
6.5-15.9 |
7.3-16.3 |
|
76 years |
6.6-15.9 |
7.3-16.3 |
|
77 years |
6.7-16.0 |
7.4-16.3 |
|
78 years |
6.8-16.0 |
7.4-16.3 |
|
79 years |
6.9-16.0 |
7.5-16.3 |
|
80 years |
7.0-16.0 |
7.5-16.3 |
|
81 years |
7.1-16.0 |
7.7-16.2 |
|
82 years |
7.2-16.0 |
7.8-16.2 |
|
83 years |
7.2-16.0 |
7.9-16.2 |
|
84 years |
7.3-16.0 |
8.0-16.2 |
|
85 years |
7.3-16.0 |
8.2-16.2 |
|
>85 years |
7.4-16.0 |
8.3-16.2 |
Interpretation
Elevated homocysteine concentrations are considered informative in patients evaluated for suspected nutritional deficiencies (vitamin B12, folate) and inborn errors of metabolism. Measurement of methylmalonic acid (MMA) distinguishes between vitamin B12 (cobalamin) and folate deficiencies, as MMA is only elevated in vitamin B12 deficiency. Treatment response can be evaluated by monitoring serum homocysteine concentrations over time.
Cautions
Other factors that may influence and increase serum homocysteine include:
-Age
-Smoking
-Poor diet/cofactor deficiencies
-Chronic kidney disease/renal disease
-Hypothyroidism
Table. Medications that may increase homocysteine concentrations include:
|
Medication |
Effect |
|
Methotrexate |
5-Methyltetrahydrofolate depletion |
|
Azuridine |
Vitamin B6 antagonist |
|
Nitrous oxide |
Inactivation of methionine synthase |
|
Phenytoin |
Interference with folate metabolism |
|
Carbamazepine |
Interference with folate metabolism |
|
Oral contraceptives |
Estrogen-induced vitamin B6 deficiency |
Clinical Reference
1. Mudd SH, Levy HL, Kraus JP: Disorders of transsulfuration. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, 2019. Accessed December 8, 2022. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225084718&bookid=2709
2. Chrysant SG, Chrysant GS: The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Rev Cardiovasc Ther. 2018 Aug;16(8):559–565. doi: 10.1080/14779072.2018.1497974
3. Refsum H, Smith AD, Ueland PM, et al: Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004 Jan;50(1):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 Nov;56(11):1686-1695
5. Sacharow SJ, Picker JD, Levy HL: Homocystinuria caused by cystathionine beta-synthase deficiency. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet] University of Washington, Seattle. 2004. Updated May 18, 2017. Accessed December 8, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1524/
Method Description
Total homocysteine is measured by stabile isotope dilution microflow liquid chromatography tandem mass spectrometry.(Unpublished Mayo method)
Day(s) Performed
Monday through FridayReport Available
3 to 5 daysTest Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
83090
NY State Approved
YesMethod Name
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
Forms
1. Biochemical Genetics Patient Information (T602)
2. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:
-Biochemical Genetics Test Request (T798)
-Cardiovascular Test Request (T724)