The role of muscle biopsy in the diagnosis of mitochondrial myopathy

Mitochondrial diseases are clinically and genetically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutations of genes encoded by either nuclear or mitochondrial DNA. In addition to clinical, laboratory and radiological findings, microscopical and biochemical analysis of affected tissues is helpful in the diagnosis. In this study, clinical, laboratory and histopathological findings of 193 patients who had muscle biopsy between 2007 and 2017 were retrospectively evaluated. They had histopathological features compatible with mitochondrial myopathy and/or respiratory chain enzyme activity assessment. There were 99 (51,2%) male and 94 (48,8%) female patients. Parental consanguinity rate was 56%. Age at first complaints ranged from birth to 15 years (median 12 months). A great majority of the patients (93,8%) had neurologic complaints, most common were hypotonia (38,3%), seizure (32,6%) and motor and mental retardation (29,5%). Hypertrophic and dilated cardiomyopathy were present in 11 and 4 patients, respectively. Renal and endocrine system involvement were seen in 8 patients, each. Most common histopathologic finding was cytochrome c oxidase (COX) deficiency (107 patients; 55,4%). This was followed by abnormal mitochondrial distribution in the form of subsarcolemmal accumulation, ragged-red or ragged-blue fibers (82 patients; 42,5%), lipid accumulation (51 patients; 26,4%) and succinic dehydrogenase (SDH) deficiency (11 patients; 5,7%). Histopathological evaluation was normal in 41 patients. Decreased respiratory chain enzyme activity was detected in 30 out of 56 patients (53,6%). 9 had isolated and 21 had multiple complex deficiency. Complex IV deficiency was the most frequent. According to the mitochondrial disease criteria, 44,3% was classified as "probable" and 35,4% as "definite". In conclusion, muscle biopsy has an important role in diagnosing mitochondrial myopathy, by microscopical investigation and respiratory chain enzyme activity measurement. Although there is not always a good correlation between clinical and histopathological features, biopsy findings may help diagnosis and direct further studies. It is important to evaluate microscopical features and respiratory chain enzyme activity together and interpret the results. If there is clinical suspicion in patients without histopathological findings, further studies such as respiratory chain enzyme activity measurement and genetic studies can be performed. Key words: Mitochondrial disease, muscle biopsy, histopathology, respiratory chain enzyme activity, childhood