Diagnostic Testing in Suspected Primary Mitochondrial Myopathy

The diagnosis of primary mitochondrial myopathy is often delayed by years due to non-specific clinical symptoms as well as variable testing of mitochondrial disorders. The aim of this review is to summarize and discuss the collective findings and novel insights regarding the diagnosing, testing, and clinical presentation of primary mitochondrial myopathy (PMM). PMM results from a disruption of the oxidative phosphorylation (OXPHOS) chain in mitochondria due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Although there are many named syndromes caused by mitochondrial mutations, this review will focus on PMM, which are mitochondrial disorders mainly affecting, but not limited to, the skeletal muscle. Clinical presentation may include muscle weakness, exercise intolerance, myalgia, and rhabdomyolysis. Although skeletal muscle and respiratory function are most frequently affected due to their high energy demand, multisystem dysfunction may also occur, which may lead to the inclusion of mitochondrial myopathies on the differential. Currently, there are no effective disease-modifying treatments, and treatment programs typically only focus on managing the symptomatic manifestations of the disease. Although the field has a large unmet need regarding treatment options, diagnostic pathways are better understood and can help shorten the diagnostic journey to aid in disease management and clinical trial enrollment.