Tissue mosaicism in the skeletal muscle and sural nerve biopsies in the MELAS syndrome

We describe a clinically full-blown MELAS patient, who had an A3243G point mutation of mitochondrial DNA (mtDNA) in muscle and blood cells, and his family members. From the proband two muscle biopsies from the vastus lateralis muscle were analyzed; one had typical ragged red fibers and focal cytochrome c oxidase deficiency and the other was completely normal. He also had a peripheral neuropathy confirmed by nerve conduction velocity and sural nerve biopsy studies. Axonal degeneration, relative loss of large myelinated fibers and paracrystalline inclusion bodies in the Schwann cells were noted. Intriguingly, the A3243G mutation of mtDNA was not found in the sural nerve biopsy. Therefore, we conclude that tissue mosaicism is present in the muscle fibers and that the mtDNA mutation may not be detected in the nerve involved as proved by pathology. We also suggest that the involvement of specific tissues in patients with mitochondrial diseases should be further determined by single fiber mtDNA analysis.