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Test Code MTHFR 5,10-Methylenetetrahydrofolate Reductase C677T, Mutation, Blood

Reporting Name

MTHFR C677T Mutation Analysis, B

Useful For

Direct mutation analysis for the MTHFR C677T mutation should be reserved for patients with coronary artery disease, acute myocardial infarction, peripheral vascular artery disease, stroke, or venous thromboembolism who have increased basal homocysteine levels or an abnormal methionine-load test.

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Whole blood


Advisory Information


Can be combined with other molecular coagulation tests:

-MTHAC / 5,10-Methylenetetrahydrofolate Reductase A1298C, Mutation, Blood

-F5DNA / Factor V Leiden (R506Q) Mutation, Blood

-PTNT / Prothrombin G20210A Mutation, Blood

-MTHP / 5,10-Methylenetetrahydrofolate Reductase C677T and A1298C Mutations, Blood



Specimen Required


Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Lavender top (EDTA) or blue top (sodium citrate)

Specimen Volume: Full tube

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.


Specimen Minimum Volume

1 mL in a 3-mL ACD tube

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Ambient (preferred) 7 days
  Frozen  14 days
  Refrigerated  14 days

Reference Values

Negative

Day(s) and Time(s) Performed

Monday through Friday; 12 p.m.

CPT Code Information

81291-MTHFR (5,10-methylenetetrahydrofolate reductase) (eg, hereditary hypercoagulability) gene analysis, common variants (eg, 677T, 1298C)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MTHFR MTHFR C677T Mutation Analysis, B In Process

 

Result ID Test Result Name Result LOINC Value
21827 Methylenetetrahydrofol Reduc Mut, B 21709-1
21828 MTHFR Interpretation 69049-5
21830 MTHFR Reviewed By No LOINC Needed

Clinical Information

Hyperhomocysteinemia is an independent risk factor for coronary artery disease, acute myocardial infarction, peripheral arterial disease, stroke, and venous thromboembolism. Homocysteine is a sulfhydryl-containing amino acid formed as an intermediary during the conversion of methionine to cystathionine. Genetic or nutrition-related disturbances (eg, deficiency of vitamins B12, B6, and folic acid) may impair the transsulfuration or remethylation pathways of homocysteine metabolism and cause hyperhomocysteinemia. The enzyme MTHFR catalyzes reduction of 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate, the major form of folate in plasma; 5-methyl tetrahydrofolate serves as a methyl donor for remethylation of homocysteine to methionine. Patients with severe MTHFR deficiency (enzymatic activity 0%-20% of normal) develop homocysteinuria, a severe disorder with a wide range of associated clinical manifestations, including developmental delay, mental retardation, and premature vascular disease. Seven unique MTHFR mutations have been associated with homocysteinuria, all among patients who were either homozygous or compound heterozygotes for 1 or more of these mutations.

 

A milder deficiency of MTHFR, with approximately 50% residual enzyme activity and marked enzyme lability to heat inactivation, is associated with a cytosine to thymine mutation at nucleotide position 677 (C677->T), encoding for an alanine-223 to valine substitution (MTHFR C677T). Patients who are homozygous for the MTHFR C677T mutation may develop hyperhomocysteinemia, especially with concurrent deficiency of vitamins B12, B6 (pyridoxine), or folic acid. This mutation is quite common, with a carrier frequency of 31% to 39% (homozygote frequency 9%-17%) among the white North American population. The MTHFR C677T mutation test is a direct assay of patient leukocyte genomic DNA.

 

For suspected hyperhomocysteinemia, we recommend that a basal plasma homocysteine level be measured. Vitamin B12, B6, and folic acid levels should be measured in patients with hyperhomocysteinemia.

Interpretation

The interpretive report will include specimen information, assay information, background information, and conclusions based on the test results (negative, heterozygous MTHFR C677T, homozygous MTHFR C677T).

Clinical Reference

1. Rees MM, Rodgers GM: Homocysteinemia: association of a metabolic disorder with vascular disease and thrombosis. Thromb Res 1993;71:337-359

2. Frosst P, Blom HF, Goyette P, et al: A candidate gene risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nature Genet 1995;10:111-113

3. Ma J, Stampfer MJ, Hennekens CH, et al: Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physician. Circulation 1996;94:2410-2416

4. Deloughery TG, Evans A, Sadeghi A, et al: Common mutation in methylenetetrahydrofolate reductase: correlation with homocysteine metabolism and late-onset vascular disease. Circulation 1996;94:3074-3078

5. Heit JA: Thrombophilia: clinical and laboratory assessment and management. In Consultative Hemostasis and Thrombosis. Fourth edition. Edited by CS Kitchens, BM Alving, CM Kessler. Saunders, 2012

Analytic Time

3 days

Reject Due To

Hemolysis

Mild OK; Gross OK

Lipemia

Mild OK; Gross OK

Icterus

NA

Other

Green top (heparin) tube or Extracted DNA

 

Method Name

Direct Mutation Analysis

Secondary ID

81648

Test Classification

This test has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

Forms

1. Coagulation Patient Information (T675) is available in Special Instructions

2. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.