Frequencies of myohistological mitochondrial changes in patients with mitochondrial DNA deletions and the common m.3243A>G point mutation.

Frequencies of typical myohistological changes such as ragged red fibers (RRF) and cytochrome c oxidase (COX)-deficient fibers have been suggested to be dependent on underlying mitochondrial DNA (mtDNA) defect. However, there are no systematic studies comparing frequencies of myohistological changes and underlying genotypes. The histopathological changes were analysed in 29 patients with genetically confirmed mitochondrial myopathies. Genotypes included multiple mtDNA deletions due to POLG1 mutations (n = 11), single mtDNA deletion (n = 10) and mtDNA point mutation m.3243A>G (n = 8). Histochemical reactions, including Gomori-trichome, COX/SDH (succinate dehydrogenase) and SDH as well as immunohistological reaction with COX-antibody against subunit I (COI) were carried out in muscle biopsy sections of all patients. The COX-deficient fibers were observed most frequently in all three patient groups. The frequencies of myopathological changes were not significantly different in the different genotypes in all three histochemical stains. However, there was a tendency to lower means and variations in patients with point mutation. Only COI-negative fibers were histochemically negative for COX activity in all patient groups. Frequency of COI-negative fibers was significantly lower in patients with mtDNA point mutation than in patients with deletions. This suggests that impact of point mutation on protein synthesis is less than that of deletions.