TISSUE DISTRIBUTION AND DISEASE MANIFESTATIONS OF THE TRNA(LYS) A-]G((8344)) MITOCHONDRIAL-DNA MUTATION IN A CASE OF MYOCLONUS EPILEPSY ANDRAGGED-RED FIBERS

This man with myoclonus epilepsy and ragged red fibres (MERRF) syndrom e due to the tRNA(Lys) A-->G((8344)) mutation of mitochondrial DNA (mt DNA) died of bronchopneumonia at 18 years of age. He had progressive c linical symptoms from 6 months of age manifesting as ataxia, myoclonic seizures, and muscle weakness. A post-mortem examination revealed 91- 99% mutated mtDNA in all 32 examined tissue samples, including various organs and different brain regions. The brain appeared without macros copic changes, but microscopic examination showed degeneration with lo ss of nerve cells and gliosis affecting the globus pallidus, substanti a nigra, red nucleus, dentate nucleus, inferior olivary nucleus, cereb ellar cortex, and the spinal cord. Skeletal muscle showed cytochrome c oxidase deficient muscle fibres with proliferation of mitochondria. I n addition to pathological changes of muscle and brain there were few morphological changes that could be attributed to his mitochondrial di sease. These data support the concept that in patients with the tRNA(L ys) A-->G((8344)) mutation who are manifesting disease there are high levels of mutated mtDNA in all tissues, but only some tissues and brai n regions are vulnerable.