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 vitamin B12 or folate

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Homocysteine, Total, S

Aliases
Lists additional common names for a test, as an aid in searching

Cystathionine beta-synthase deficiency

Methylenetetrahydrofolate reductase deficiency (MTHFR)

MTHFR deficiency

Methionine synthase deficiency

Cobalamin (Cbl) metabolism

Methyl-Cobalamin deficiency

Adenosyl-cobalamin deficiency

Cbl C2 deficiency

Cbl D2 deficiency

Cbl F3 deficiency

Cbl D-Var1 deficiency

Cbl E deficiency

Cbl G deficiency

Transcobalamin II deficiency:

Adenosylhomocysteinase (AHCY) deficiency

Glycine N-methyltransferase (GNMT) deficiency

Methionine adenosyltransferase (MAT) I/III deficiency

Cobalamin C2 deficiency

Cobalamin D2 deficiency

Cobalamin F3 deficiency

Cobalamin D-Variant 1 deficiency

Cobalamin E deficiency

Cobalamin G deficiency

Specimen Type
Describes the specimen type validated for testing

Serum

Necessary Information

Patient's age and sex are required.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube:

Preferred: Red top

Acceptable: Serum gel tube

Specimen Volume: 1 mL

Collection Instructions: Centrifuge and aliquot serum into plastic vial within 4 hours of collection.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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)

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

0.3 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 28 days
Frozen 309 days
Ambient 28 days

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 vitamin 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 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
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. 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 October 16, 2019. 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;50:3-32

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;56:1686-1695

5. Sacharow SJ, Picker JD, Levy HL: Homocystinuria caused by cystathionine beta-synthase deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet] University of Washington, Seattle. 2004. Updated May 18, 2017. Accessed September 11, 2020. Available at www.ncbi.nlm.nih.gov/books/NBK1524/

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Total homocysteine is measured by stabile isotope dilution microflow liquid chromatography tandem mass spectrometry.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

2 to 5 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

1 week

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

83090

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
HCYSS Homocysteine, Total, S 13965-9
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
35836 Homocysteine, Total, S 13965-9

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
Test Changes - Specimen Information 2021-12-13