EP.08Highly asymmetrical distribution of muscle wasting correlated with heteroplasmy level in a patient suffering from a mitochondrial myopathy with single deletion of mitochondrial DNA

Abstract

Mitochondrial diseases are a heterogeneous group of pathologies, which can be caused by either punctual mutations or unique deletion of mitochondrial DNA (mtDNA) or by mutations of nuclear maintenance genes (multiple deletions or depletion of mtDNA). We report a sporadic case of mitochondrial myopathy with highly asymmetrical distribution in a 45 years old man from Vietnamese origin. Since age of 34, the patient presented with progressive ophthalmoplegia and ptosis, right facial weakness, left weakness and atrophy (predominant in the upper limb. No variability was reported. There was no deficiency in the right limbs. There were no sensory symptoms but deep tendon reflexes were abolished. There was no cerebellar syndrome, no hypoacousia and no parkinsonism. Cardiac function was normal; CK levels were elevated à 671UI/l. Electroneuromyography (ENMG) showed diffuse myogenic alterations in face and limbs with spontaneous activity, much more pronounced on the left side. Biopsy performed in the left deltoid showed numerous ragged red fibers and cox negative fibers. PCR and Southern-blot revealed in muscle a single mtDNA deletion assayed by PCR and Southern Blot with percentage of heteroplasmy of 50%. Mitochondrial alterations were much less pronounced in the right deltoid muscle (presenting no weakness) and no mtDNA deletion was detected. Analyses in other tissues (blood, urine, oral cells) were negative. This observation highlights the correlation between the degree of heteroplasmy for the unique mt-DNA deletion, mitochondrial histopathological lesions and the muscle wasting, highly asymmetrical in this patient. This is a very interesting case of asymmetrical myopathy caused by mtDNA unique deletion, highlighting the fact that heteroplasmy in mitochondrial disease results in a balance between healthy and pathological cellular outcomes, and may cause such unusual phenotypes. In case of mitochondrial diseases, functional and molecular explorations in the most affected tissue is crucial.