P.57Isolated mitochondrial myopathy is common presentation in A3243G-related mitochondrial diseases

Abstract

The A3243G mutation in the mt-tRNA(Leu) gene, first described in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes (MELAS), accounts for approximately 80% of mutations in individuals with Melas syndrome. Although originally described in patient with a classical syndrome of Melas, the A3243G mutation is increasingly recognized to exhibit marked phenotypic heterogeneity. This paper describes the clinical, laboratory and histopathology features of an unusual phenotype in 6 family harboring the A3243G 'Melas' mutation. We present all the cases with isolated myopathy and 3 patients developed mid-life respiratory failure necessitating non-invasive ventilator support. Brain MRI excluded the lesions of the central nerve system. Mitochondrial histochemical abnormalities included excessive ragged-red fibers, COX-deficient fibers and lipid storage fibers and mtDNA sequencing identified the A3243G mutation commonly associated with the Melas phenotype. This cases extends the evolving phenotypic spectrum of the A3243G mutation and emphasizes that it may cause isolated mitochondrial myopathy, with remarkable histochemical abnormalities in muscle. Our findings support consideration of screening of this gene in cases of isolated mitochondrial myopathy.