P.17.14 Myohistological mitochondrial changes in patients with mtDNA singular deletions, multiple deletions and A3243G point mutation

Abstract

Chronic progredient external opthalmoplegia (CPEO) and the MELAS syndrome are the most common disorders that are associated with mitochondrial changes. CPEO is either associated with singular or multiple mtDNA deletions, whereas, MELAS is usually caused by the A3243G point mutation on mtDNA. The basic diagnostic criteria for these diseases are histopathological changes in muscle biopsy. So far, a systematic study comparing myopathological changes in these three groups has not yet been reported. We analysed muscle biopsies from 29 patients (16 males, 13 females) with mitochondrial diseases to investigate whether the genetic background influences the incidence of histopathological changes. 10 patients had singular mtDNA deletions and 11 patients had multiple deletions due to POLG1 nuclear mutations. Additionally, 8 patients harboured the MELAS A3243G point mutation. Freeze-dried sections of muscle biopsies were stained for histochemical reactions with Gomori trichrome, COX/SDH and SDH stainings. Furthermore, immunohistological reaction with COX antibody was also carried out. In all three groups, the COX-negative fibers were observed most frequently. The frequency of RRF was about a third of the COX-negative fibers. Dark blue COX-negative fibers were significantly higher than the hyperreactive fibers in SDH staining. The parallel analysis of individual pathological fibres showed that, in all three groups, all COX negative fibers had pathological changes also in other stainings and immunohistology. The results confirm that the COX/SDH double staining is the most sensitive method in the diagnosis compared to the other two stainings. Nevertheless, these changes could have been occurred due to the high overlap between the three groups in each individual cases.