A 41-year-old woman presented with recurrent rhabdomyolysis over one year. She noticed non-specific muscle pain dating 12 years before the presentation. In 2022, she was diagnosed with coronary artery disease requiring intervention. Following the procedure, she developed generalized malaise and severe muscle pain, accompanied by elevated creatinine and CK to 5,000 U/L; she was diagnosed with statin-induced nephropathy and myopathy. Despite statin discontinuation, she continued to have muscle pain triggered by mild physical activity. In September 2023, she experienced a severe episode of myalgias and weakness; her CK was 15,000 U/L. Clinical Whole-Exome sequencing was negative. mtDNA sequencing from buccal swab identified an 11% mutation load in MT-TF (m.610T>C) and 6% heteroplasmic variant in MT-COIII (m.9544G>A). Muscle biopsy showed 25-35% COX-negative fibers with no ragged-red fibers, muscle mtDNA analysis revealed 8.2% heteroplasmy of the MT-TF variant but 55% mutation load of the MT-COIII variant, supporting the diagnosis of mitochondrial myopathy

This report of a metabolic myopathy due to a novel MT-COIII variant exemplifies several obstacles we face in diagnosing patients with metabolic myopathies. The initial presentation is often nonspecific, delaying correct referral. Also, the current commonly used genetic panels for myopathies do not include mtDNA analysis, thus underestimating these conditions. Furthermore, mtDNA disorders are highly tissue-specific and may require target tissue genetic and biochemical analyses of the affected tissues to confirm the diagnosis