Medical_Policy

Highmark Commercial Medical Policy - Pennsylvania

Medical Policy:	L-176-004
Topic:	MTHFR Variant Analysis for Hyperhomocysteinemia
Section:	Laboratory
Effective Date:	November 13, 2017
Issue Date:	November 13, 2017
Last Reviewed:	June 2017

Hyperhomocysteinemia generally refers to mild to moderate elevations of plasma homocysteine levels, which may be defined as 15 to 40 μmol/L. It may be caused by nutritional deficiencies, various medical conditions, certain drugs, smoking, and inherited factors — such as MTHFR gene variants.

MTHFR is involved in folate metabolism. The major circulating form of folate is key to converting homocysteine into methionine.

This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical circumstances may warrant individual consideration, based on review of applicable medical records.

Policy Position Coverage is subject to the specific terms of the member’s benefit plan.

MTHFR variant analysis for hyperhomocysteinemia is considered experimental/investigational (E/I) and therefore, non-covered.

E/I molecular and genomic (MolGen) tests refer to assays involving chromosomes, DNA, RNA, or gene products that have insufficient data to determine the net health impact, which typically means there is insufficient data to support that a test accurately assesses the outcome of interest (analytical and clinical validity), significantly improves health outcomes (clinical utility), and/or performs better than an existing standard of care medical management option. Such tests are also not generally accepted as standard of care in the evaluation or management of a particular condition.

In the case of MolGen testing, FDA clearance is not a reliable standard given the number of laboratory developed tests that currently fall outside of FDA oversight and FDA clearance often does not assess clinical utility.

Procedure Codes

81291

Professional Statements and Societal Positions

As part of the Choosing Wisely campaign, the American College of Medical Genetics and Genomics (2015) released “Five Things Physicians and Patients Should Question,” which states:⁶

“Don’t order MTHFR genetic testing for the risk assessment of hereditary thrombophilia. The common MTHFR gene variants, 677C>T and 1298A>G, are prevalent in the general population. Recent meta-analyses have disproven an association between the presence of these variants and venous thromboembolism.”

The American College of Medical Genetics and Genomics (ACMG, 2013) states:

“It was previously hypothesized that reduced enzyme activity of MTHFR led to mild hyperhomocysteinemia which led to an increased risk for venous thromboembolism, coronary heart disease, and recurrent pregnancy loss. Recent meta-analyses have disproven an association between hyperhomocysteinemia and risk for coronary heart disease and between MTHFR polymorphism status and risk for venous thromboembolism. There is growing evidence that MTHFR polymorphism testing has minimal clinical utility and, therefore should not be ordered as a part of a routine evaluation for thrombophilia.”

The American College of Obstetricians and Gynecologists (ACOG, 2013) states:

“Because of the lack of association between either heterozygosity or homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and any negative pregnancy outcomes, including any increased risk for venous thromboembolism, screening with either MTHFR mutation analyses or fasting homocysteine levels is not recommended.”

The National Society of Genetic Counselors (NSGC, 2005) state that MTHFR variant testing is specifically not justified in the case of recurrent pregnancy loss based on available studies.

Place of Service: Outpatient

Experimental/Investigational (E/I) services are not covered regardless of place of service.

MTHFR variant analysis for hyperhomocysteinemia is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of business

Denial Statements

Services that do not meet the criteria of this policy will be considered experimental/investigational (E/I). A network provider can bill the member for the experimental/investigational service. The provider must give advance written notice informing the member that the service has been deemed E/I. The member must be provided with an estimate of the cost and the member must agree in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

Links

Link to References

Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

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