Objective: to perform a standardized histopathological characterization of muscle biopsy findings from a cohort of 30 patients diagnosed with mitochondrial myopathy. Histopathological data are subsequently correlated with clinical, biochemical, and genetic data to obtain useful information in the clinical management of patients affected by mitochondrial myopathy.
Methods: CK and basal lactate dosage, electrophysiological study, brain MRI, muscle biopsy, respiratory chain (RC) enzyme dosage and genetic investigation with mitochondrial DNA analysis and panel for nuclear genes responsible for mitochondrial myopathy, on muscle samples.
Results: PEO was the prevalent symptom at onset in our cohort. Peripheral neuropathy was identified in 20% of cases, whereas CNS anomalies were identified in 25% of cases. Serum CK levels and basal lactate values were in most cases normal. On muscle biopsy, the most frequent aspects were the presence of ragged-red and COX- fibers, present in 80%. Analysis of individuals carrying mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) mutations compared to those without identified mutations revealed distinctive patterns. Specifically, individuals harboring pathogenetic mtDNA variants exhibited a high percentage of fibers with COX deficiency and more frequent abnormalities in RC enzyme levels. In contrast, there were no significant differences observed between individuals with nuclear mutations and those lacking molecular definition, in terms of histological or biochemical findings.
Conclusion: this study confirms the significant phenotypic variability observed among patients with mitochondrial myopathies, which frequently poses challenges in directing genetic investigations. Nonetheless, the systematic analysis of muscle biopsies offers a valuable aid when reaching a firm diagnosis.