Appeal type: Experimental/Investigational
Decision: Overturned

Diagnosis: Central Nervous System/Neuromuscular Disorder. 
Treatment: Genetic Testing. 
The insurer denied nuclear encoded mitochondrial gene genomic sequence analysis panel. 

The denial is upheld. 

The patient is a female with a history of premature birth, Turner syndrome, weakness, cerebral palsy, and scoliosis. Her weakness began and initially consisted of fluctuating ptosis and exercise intolerance. She was diagnosed with myasthenia gravis, but did not have anti-acetylcholine receptor antibodies to confirm this diagnosis. Because she was diagnosed with myasthenia gravis, she was initially treated with mestinon, which was not effective. She was subsequently treated with periodic intravenous immunoglobulins (IVIg), which seemed to lead to improvement after about one year of treatments. Eventually, however, she stopped responding to the IVIg treatments. In an attempt to confirm the diagnosis of myasthenia gravis, the patient underwent repetitive nerve stimulation. The results of this test revealed no evidence of a neuromuscular junction disorder, thus demonstrating that she likely does not have myasthenia gravis. However, the study did show some evidence of a non-irritative, non-inflammatory myopathy, thus suggesting that she does have a muscle disease. The patient's present symptoms consist of bilateral ptosis, occasional double vision, and proximal arm and leg weakness. The biological basis for this weakness is unknown. She has undergone a comprehensive neuromuscular gene panel analysis, which revealed several variants of unknown significance only. Additional work up has included complete blood count (CBC), comprehensive metabolic panel (CMP), brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis, all of which has been unremarkable. The patient's physician suspects that the patient might have a mitochondrial myopathy. To test for this possibility, the provider has ordered a Nuclear Encoded Mitochondrial Genes Genomic Sequence Analysis Panel. The subject under review is whether this testing is likely to be more beneficial for the patient's condition than any standard treatment.

Mitochondria are intracellular organelles that play key roles in respiration and energy production. Disorders of mitochondria can affect many organ systems, but nerve and muscle tissues are most commonly affected. As a result, patients with muscle weakness sometimes have disorders of mitochondria. Some of the diseases affecting mitochondrial function are genetic in origin. Most of the genes that encode mitochondrial proteins are located within the cell's nucleus. Thus, to identify nuclear genes containing mutations that adversely affect mitochondrial function, one can order a Nuclear Encoded Mitochondrial Genes Genomic Sequence Analysis Panel. This test uses next generation sequencing to investigate and identify potential mutations in hundreds of nuclear encoded mitochondrial genes. However, even if a mutation is identified in a nuclear encoded mitochondrial gene, the clinical significance of this finding is usually not known. Furthermore, even if the identified mutation is known or suspected to have clinical significance, there are no specific therapies available to help the patient or to improve the patient's quality of life.