MITOCHONDRIAL DISEASES & METABOLIC MYOPATHIES: P.317 A novel m.9143T>C variant – intercurrent severe lactate acidosis and immunodeficiency as an extension of the phenotypic spectrum in MT-ATP6 mutations

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Mutations in the MT-ATP6 are a well-known cause of maternally inherited mitochondrial disorders associated with a wide range of clinical phenotypes. Here, we present a 31-year-old female with type 1 diabetes mellitus, recurrent severe lactic acidosis and ketoacidosis, recurrent infections with suspected immunodeficiency with T cell lymphopenia and hypogammaglobulinaemia, as well as proximal tetraparesis with severe muscle and limb pain and rapid physical exhaustion. Muscle biopsy and respiratory chain activities were normal. Single-exome sequencing revealed an unreported variant in the MT-ATP6 gene: m. 9143T>C. Pathogenicity was confirmed through segregation studies. The highest mutation load was found in muscle (99.67% levels of mtDNA heteroplasmy). Interestingly, acute episodic metabolic and physical decompensation was documented to be a common clinical feature in MT-ATP6 mutations, suggesting, that the clinical spectrum might be expanded in these mutations.