Highmark Commercial Medical Policy - Pennsylvania
Medical Policy: L-179-005
Topic: Leber Hereditary Optic Neuropathy (LHON) Genetic Testing
Section: Laboratory
Effective Date: November 13, 2017
Issue Date: November 13, 2017
Last Reviewed: March 2017

LHON is a mitochondrial disorder that mainly affects the eye. It is characterized by bilateral painless subacute vision loss that begins in the second and third decades of life. It usually has onset between 15-30 years of age, and leads to rapid, progressive blindness. Visual acuity usually deteriorates to 20/200 or worse.

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.

LHON Known Familial Mutation Testing may be considered medically necessary when the following criteria are met:

LHON Targeted Mutation Analysis (G3460A, G11778A and T14484C) may be considered medically necessary when the following criteria are met:

Whole mtDNA Sequencing may be considered medically necessary when the following criteria are met:

Procedure Codes
81401, 81403, 81460

Professional Statements and Societal Positions

No evidence-based U.S. testing guidelines were identified for LHON.

Although not specific to genetic testing for LHON, the Mitochondrial Medicine Society (2015) developed consensus recommendations for the diagnosis and management of mitochondrial disease. Testing strategies, including strategies for genetic testing, were discussed.

  • Recommendations for DNA testing include the following:
    • “Massively parallel sequencing/NGS of the mtDNA genome is the preferred methodology when testing mtDNA and should be performed in cases of suspected mitochondrial disease instead of testing for a limited number of pathogenic point mutations.
    • Patients with a strong likelihood of mitochondrial disease because of a mtDNA mutation and negative testing in blood, should have mtDNA assessed in another tissue to avoid the possibility of missing tissue-specific mutations or low levels of heteroplasmy in blood; tissue-based testing also helps assess the risk of other organ involvement and heterogeneity in family members and to guide genetic counseling.
    • Heteroplasmy analysis in urine can selectively be more informative and accurate than testing in blood alone, especially in cases of MELAS due to the common m.3243 A>G mutation.
    • When considering nuclear gene testing in patients with likely primary mitochondrial disease, NGS methodologies providing complete coverage of known mitochondrial disease gene is preferred. Single-gene testing should usually be avoided because mutations in different genes can produce the same phenotype. If no mutation is identified via known NGS panels, then whole exome sequencing should be considered.”

The European Federation of Neurological Sciences (2009) provide consensus-based guidelines for LHON genetic testing: "If the phenotype suggests syndromic mitochondrial disorder due to mtDNA point mutations (MELAS, MERRF, NARP, LHON), DNA-microarrays using allele-specific oligonucleotide hybridisation, real-time-PCR or single-gene sequencing are indicated."

The Clinical Molecular Genetics Society of the United Kingdom (2008) provided practice-based guidelines for the molecular diagnosis of mitochondrial disease: "Investigation for the G3460A, G11778A and T14484C mutations are indicated for all LHON referrals."

A 2016 expert-authored review suggests the following testing strategy for those with a known or suspected diagnosis of LHON:

  • Three common mtDNA pathogenic variants account for 90%-95% of LHON. Targeted analysis for one of these three variants should be performed first."
  • "A multi-gene panel that includes the mitochondrial genes that encode subunits of NADH dehydrogenase, MT-ND1, MT-ND2, MT-ND4, MT-ND4L, MT-ND5, and MT-ND6, which are known to cause LHON and other genes of interest may also be considered."
  • "Complete mtDNA sequencing may be considered if use of targeted testing and/or a multi-gene panel did not identify a pathogenic variant, clinical suspicion remains high, and there is no evidence of paternal transmission.

For those seeking predictive testing (e.g. they are not currently affected), this review states:

  • "Testing of at-risk asymptomatic adults for LHON is possible. Such testing is not useful in predicting age of onset, severity, or rate of progression in asymptomatic individuals."
  • Testing of asymptomatic individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists is not considered appropriate.

Place of Service: Outpatient

LHON genetic testing 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 not be considered medically necessary. A network provider cannot bill the member for the denied service unless: (a) the provider has given advance written notice, informing the member that the service may be deemed not medically necessary; (b) the member is provided with an estimate of the cost; and (c) the member agrees in writing to assume financial responsibility in advance of receiving the service. The signed agreement must be maintained in the provider’s records.

Links




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.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer: If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

Insurance or benefit/claims administration may be provided by Highmark, Highmark Choice Company, Highmark Coverage Advantage, Highmark Health Insurance Company, First Priority Life Insurance Company, First Priority Health, Highmark Benefits Group, Highmark Select Resources, Highmark Senior Solutions Company or Highmark Senior Health Company, all of which are independent licensees of the Blue Cross and Blue Shield Association, an association of independent Blue Cross and Blue Shield plans.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.