Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
Mitochondrial disorder (MD) refers to approximately 40 different disorders, presenting mostly in childhood (usually by age 10), affecting one or more organ systems and varying in degree of dysfunction. All disorders are caused by mutations in either the mitochondrial and/or nuclear DNA. The prevalence of mitochondrial disorders is approximately 1 in 5000 births in the United States. No known cure exists for any of the disorders. Currently less than half of the named disorders have an identified genetic cause, and the presence of the gene variant does not predict the severity of the disorder. While larger expanded panels (e.g. GeneDx®) or mitochondrial genome sequencing may be useful in diagnosing a mitochondrial disorder, whole exome sequencing does not sequence mtDNA.
Some of the more common named mitochondrial disorders are: Leigh Syndrome (LS), mitochondrial encephalomyopathy lactic acidosis with stroke-like episodes (MELAS), Leber hereditary optic neuropathy (LHON), and neuropathy ataxia retinitis pigmentosa (NARP). The diagnosis of a mitochondrial disorder can be difficult, as symptoms often mimic other disorders such as Autism, and Parkinson’s. In addition, the symptoms of the various mitochondrial disorders often overlap. Standard tests used in diagnosing a mitochondrial disorder may include:
Levels of certain substances in a sample of blood or cerebrospinal fluid
Magnetic resonance spectroscopy (detects abnormalities in the brain's chemical makeup)
Imaging studies of the brain such as MRI or CT scan
Electrocardiography and echocardiography
Treatment of mitochondrial disease is largely supportive, as there are no specific therapies that impact the natural history of the disorders.
Genetic testing (single gene or multi-gene panels) to confirm the diagnosis of a mitochondrial disorder may be considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Pre- and post- genetic counseling as an adjunct to genetic testing itself is considered medically necessary.
Genetic testing of a mitochondrial disorder is considered medically appropriate if ANY ONE of the following criteria are met:
To confirm the diagnosis of a mitochondrial disorder with ALL of the following:
Clinical signs and symptoms are consistent with a specific mitochondrial disorder
The diagnosis cannot be made with certainty by clinical and/or biochemical evaluation (e.g., one or more of the standard tests such as metabolite analysis of blood and/or urine sample)
Preconception evaluation if ALL of the following are met:
There is a diagnosed mitochondrial disorder in a parent, sibling, or previous child of sufficient severity to cause impairment of quality of life or functional status
The specific genetic variance has been documented to be associated with a mitochondrial disorder
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
Mitochondrial disorders are either inherited maternally, or when both parents carry the recessive trait. When a disorder is severe enough to cause impairment and/or disability in a sibling or previous child of either parent, genetic testing prior to future reproductive decisions is a reasonable choice.
BlueCross BlueShield Association. Evidence Positioning System. (10:2020). Genetic testing for mitochondrial disorders (2.04.117). Retrieved February 11, 2021 from https://www.evidencepositioningsystem.com/. (31 articles and/or guidelines reviewed)
Chang, x., Wu, Y., Zhou,J., Meng, H., Zhang, W., & Guo, J. (2020). A meta-analysis and systematic review of Leigh syndrome: clinical manifestations, respiratory chain enzyme complex deficiency, and gene mutations. Medicine, 99 (5), e18634. (Level 1 evidence)
Clinical Molecular Genetics Society. (2004; last updated 2008). Practice guidelines for the molecular diagnosis of mitochondrial diseases. Retrieved May 21, 2019 from https://www.acgs.uk.com/quality/best-practice-guidelines/.
Mitochondrial Medicine Society. (2014). Diagnosis and management of mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Retrieved May 21, 2019 from http://www.mitosoc.org/.
Ng, Y. S., Hardy, S. A., Shrier, V., Quaghebeur, G., Mole, D. R., Daniels, M. J., et al. (2016). Clinical features of the pathogenic m.5540G>A mitochondrial transfer RNA tryptophan gene mutation. Neuromuscular Disorders, 26 (10), 702-705. (Level 4 evidence)
Sanghivi, H., Singh, R., Morrin, H., & Rajkumar, A.P. (2020). Systematic review of genetic association studies in people with Lewy body dementia. International Journal of Geriatric Psychiatry, 35 (5), 436-448. (Level 2 evidence)
ORIGINAL EFFECTIVE DATE: 1/10/2015
MOST RECENT REVIEW DATE: 4/8/2021
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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