TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: HCYSS    
Homocysteine, Total, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

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

 

Screening and monitoring patients suspected of or confirmed with an inherited disorder of methionine metabolism

 

Evaluating individuals with suspected deficiency of B12 or folate

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 (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 also 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 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, quantitative acylcarnitines, methylmalonic acid, 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.

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 Provides information to assist in interpretation of the test results

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 Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Other factors that may influence and increase serum homocysteine include:

-Age

-Smoking

-Poor diet/cofactor deficiencies

-Chronic kidney disease/renal disease

-Hypothyroidism

 

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 Recommendations for in-depth reading of a clinical nature

1. Harvey Mudd S, Levy HL, Kraus JP: Disorders of transsulfuration. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill, 2014. Accessed Oct 16, 2019. Available at ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62675596

2. Chrysant SG, Chrysant GS: The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Review of Cardiovascular Therapy, 2018;16(8):559–565 Available at doi.org/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 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

5. Sacharow SJ, Picker JD, Levy HL: Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. In GeneReviews Edited by MP Adam, HH Ardinger, RA Pagon et al: University of Washington, Seattle. Updated 2017 May 18. Available at www.ncbi.nlm.nih.gov/books/NBK1524/