GP224 Multisystem mitochondrial diseases in children with maternally inherited complex I deficiency. (June 2019)

• Record Type: Journal Article
• Authors: Danhelovska, Tereza; Kolarova, Hana; Langer, Jan; Berankova, Kamila; Hansikova, Hana; Tesarova, Marketa; Honzik, Tomas; Zeman, Jiri
• Is Part Of: Archives of disease in childhood. Volume 104:(2019)Supplement 3
• Page Start: A121
• Page End: A122
• Publication Date: 2019-06
• Subjects: Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2019-epa.283
• Languages: English
• ISSNs: 0003-9888

Abstract

Abstract : 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 <60%, who developed MELAS syndrome with stroke-like episodes. In last two children, the diseases started with optic neuropathy but both children transitioned later to multisystem diseases compatible with MELAS syndrome. The activities of CI in isolated muscle mitochondria were decreased in most patients and analyses with [1– 14 C]pyruvate, [U- 14 C]malate and [1, 4– 14 C]succinate substrates revealed decreased CO2 production in some patients. 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.