GP224 Multisystem mitochondrial diseases in children with maternally inherited complex I deficiency

Mitochondrial disorders (MD) in childhood represent a heterogeneous group of disease. The most common cause of MD is respiratory chain complex I (CI) deficiency, which may be caused by mutations in either nuclear or the mitochondrial DNA (mtDNA). In the cohort of 106 unrelated families with mtDNA mutations from our region with 10,5 million of inhabitants, the multisystem MD due mtDNA mutations in MT-ND genes for structural subunits of CI were recognized in 12 families with 13 affected children. Results In the group of 13 patients, altogether 8 different heteroplasmic mtDNA mutations in MT-ND genes were found. Mutations in MT-ND5 gene were most frequent including one novel mutation m.13091T>C. Six children with the mutation heteroplasmy >60% had Leigh syndrome and significantly worse prognosis than five patients with heteroplasmy Conclusions Children with the multisystem MD due to CI deficiency and heteroplasmic mtDNA mutations usually develop Leigh or MELAS syndromes and represent approximately 11% of families with maternally inherited MD diagnosed in our region. Early onset of the disease and higher level of heteroplasmy of mtDNA mutations resulted in Leigh phenotype with worse prognosis. Supported by projects AZV 17–30965A and RVO VFN 61514.