ACMG practice guideline: lack of evidence for MTHFR polymorphism testing.
General
Guideline Title
ACMG practice guideline: lack of evidence for MTHFR polymorphism testing.
Bibliographic Source(s)
- Hickey SE, Curry CJ, Toriello HV. ACMG practice guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013 Feb;15(2):153-6. [77 references] PubMed
Guideline Status
This is the current release of the guideline.
Recommendations
Major Recommendations
American College of Medical Genetics and Genomics (ACMG) Recommendations
- 5,10-methylenetetrahydrofolate reductase ( MTHFR ) polymorphism genotyping should not be ordered as part of the clinical evaluation for thrombophilia or recurrent pregnancy loss.
- MTHFR polymorphism genotyping should not be ordered for at-risk family members.
- A clinical geneticist who serves as a consultant for a patient in whom an MTHFR polymorphism(s) is found should ensure that the patient has received a thorough and appropriate evaluation for his or her symptoms.
- If the patient is homozygous for the “thermolabile” variant c.665C→T, the geneticist may order a fasting total plasma homocysteine, if not previously ordered, to provide more accurate counseling.
- MTHFR status does not change the recommendation that women of childbearing age should take the standard dose of folic acid supplementation to reduce the risk of neural tube defects as per the general population guidelines (Zacho et al., 2011; De Stefano et al., 2000; Institute of Medicine, Food and Nutrition Board, 1998; “Prevention of neural tube,” 1991; Czeizel & Dudás, 1992; “Recommendations for the use of folic acid,” 1992; Toriello, 2011).
Clinical Algorithm(s)
None provided
Scope
Disease/Condition(s)
Thrombophilia
Guideline Category
- Assessment of Therapeutic Effectiveness
- Counseling
- Evaluation
Clinical Specialty
- Family Practice
- Hematology
- Medical Genetics
- Obstetrics and Gynecology
Intended Users
- Physicians
Guideline Objective(s)
To review the latest evidence on 5,10-methylenetetrahydrofolate reductase ( MTHFR ) polymorphism testing as part of a routine evaluation for thrombophilia
Target Population
Women of childbearing age and patients at risk for thrombophilia
Interventions and Practices Considered
- 5,10-methylenetetrahydrofolate reductase ( MTHFR ) polymorphism testing (not recommended)
- Evaluation of symptoms in patients in whom an MTHFR polymorphism(s) is found
- Fasting total plasma homocysteine
- Folic acid supplementation
Major Outcomes Considered
Not stated
Methodology
Methods Used to Collect/Select the Evidence
- Hand-searches of Published Literature (Primary Sources)
- Hand-searches of Published Literature (Secondary Sources)
- Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence
The guideline authors searched PubMed and the Cochrane Database of Systematic Reviews from January 1995 to the present. In the literature search, priority was given to original research, with highest emphasis on meta-analyses, followed by case-control and cohort studies. The Literature search excluded review articles, case reports, and articles in languages other than English. Bibliographies of articles deemed to be of the highest quality for their specific topic were combed for additional articles that may have been missed by the initial literature search. In addition, the guidelines of other professional bodies on the same, or related, topic were reviewed.
The databases were searched using the following terms: MTHFR, MTHFR polymorphism, MTHFR thermolabile variant, methylenetetrahydrofolate reductase, and hyperhomocysteinemia. Combined searches were done on specific questions of interest including: MTHFR and stroke, MTHFR and recurrent pregnancy loss, MTHFR and venous thromboembolism, and MTHFR and coronary artery disease. The same combined searches were done for hyperhomocysteinemia and stroke, etc.
Number of Source Documents
Not stated
Methods Used to Assess the Quality and Strength of the Evidence
- Not stated
Rating Scheme for the Strength of the Evidence
Not applicable
Methods Used to Analyze the Evidence
- Review
Description of the Methods Used to Analyze the Evidence
The articles were reviewed by the working group who provided expert consensus.
Methods Used to Formulate the Recommendations
- Expert Consensus
Description of Methods Used to Formulate the Recommendations
Not stated
Rating Scheme for the Strength of the Recommendations
Not applicable
Cost Analysis
A formal cost analysis was not performed and published cost analyses were not reviewed.
Method of Guideline Validation
- Internal Peer Review
Description of Method of Guideline Validation
The final manuscript was reviewed by the American College of Medical Genetics and Genomics (ACMG) Policy & Practice Guideline Committee Members, followed by the Board of Directors, and then opened up for general college membership comment.
Evidence Supporting the Recommendations
References Supporting the Recommendations
- Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992 Dec 24;327(26):1832-5. PubMed
- De Stefano V, Casorelli I, Rossi E, Zappacosta B, Leone G. Interaction between hyperhomocysteinemia and inherited thrombophilic factors in venous thromboembolism. Semin Thromb Hemost. 2000;26(3):305-11. [32 references] PubMed
- Institute of Medicine, Food and Nutrition Board. Dietary reference intakes: thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin, and choline. Washington (DC): National Academy Press; 1998.
- Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991 Jul 20;338(8760):131-7. PubMed
- Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. MMWR Recomm Rep. 1992 Sep 11;41(RR-14):1-7. [14 references] PubMed
- Toriello HV, Policy and Practice Guideline Committee of the American College of Medical. Policy statement on folic acid and neural tube defects. Genet Med. 2011 Jun;13(6):593-6. PubMed
- Zacho J, Yazdanyar S, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG. Hyperhomocysteinemia, methylenetetrahydrofolate reductase c.677C>T polymorphism and risk of cancer: cross-sectional and prospective studies and meta-analyses of 75,000 cases and 93,000 controls. Int J Cancer. 2011 Feb 1;128(3):644-52. PubMed
Type of Evidence Supporting the Recommendations
The type of evidence supporting the recommendations is not specifically stated.
Benefits/Harms of Implementing the Guideline Recommendations
Potential Benefits
Appropriate use of 5,10-methylenetetrahydrofolate reductase ( MTHFR ) polymorphism testing in routine evaluation for thrombophilia
Potential Harms
Not stated
Implementation of the Guideline
Description of Implementation Strategy
An implementation strategy was not provided.
Institute of Medicine (IOM) National Healthcare Quality Report Categories
IOM Care Need
- Staying Healthy
IOM Domain
- Effectiveness
- Patient-centeredness
Identifying Information and Availability
Bibliographic Source(s)
- Hickey SE, Curry CJ, Toriello HV. ACMG practice guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013 Feb;15(2):153-6. [77 references] PubMed
Adaptation
Not applicable: The guideline was not adapted from another source.
Date Released
2013 Feb
Guideline Developer(s)
- American College of Medical Genetics and Genomics - Professional Association
Source(s) of Funding
American College of Medical Genetics and Genomics
Guideline Committee
Not stated
Composition of Group That Authored the Guideline
Authors : Scott E. Hickey, MD, FACMG, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA; Cynthia J. Curry, MD, FACMG, Genetic Medicine Central California, University of California, San Francisco–Fresno, Fresno, California, USA; Helga V. Toriello, PhD, FACMG, Department of Pediatrics/Human Development, Spectrum Health Hospitals and College of Medicine, Michigan State University, Grand Rapids, Michigan, USA
Financial Disclosures/Conflicts of Interest
The authors declare no conflict of interest.
Guideline Status
This is the current release of the guideline.
Guideline Availability
Available from the American College of Medical Genetics and Genomics (ACMG) Web site.
Availability of Companion Documents
None available
Patient Resources
None available
NGC Status
This NGC summary was completed by ECRI Institute on November 19, 2013.
Copyright Statement
This NGC summary is based on the original guideline, which is subject to the guideline developer’s copyright restrictions.
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