BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for Mitochondrial Disorders

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018

DESCRIPTION

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:

Treatment of mitochondrial disease is largely supportive, as there are no specific therapies that impact the natural history of the disorders.

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION 

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.

SOURCES

American College of Medical Genetics and Genomics. (2013, March). ACMG position statement on prenatal/preconception expanded carrier screening. Genetics in Medicine, 15 (6), 482-483.

BlueCross BlueShield Association. Evidence Positioning System. (6:2018). Genetic Testing for Mitochondrial Disorders (2.04.117). Retrieved May 20, 2019 from https://www.evidencepositioningsystem.com/.  (28 articles and/or guidelines reviewed)

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/.

Khan, N., Govindaraj, P., Meena, A. & Thangaraj, T. (2015). Mitochondrial disorders: Challenges in diagnosis & treatment. Indian Journal of Medical Research, 141 (1), 13-26. (Level 5 evidence)

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)

ORIGINAL EFFECTIVE DATE:  1/10/2015

MOST RECENT REVIEW DATE:  6/13/2019

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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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