Mitochondrial DNA disorders

Over 100 pathogenic point mutations and 200 deletions, insertions, and rear rangements have been identified since the first mitochondrial DNA mutations were described in 1988. About 60% of the point mutations affect mitochondr ial tRNAs, 35% affect polypeptide subunits of the respiratory chain, and 5% affect mitochondrial ribosomal RNAs. The clinical phenotypes of mitochondr ial tRNA disease span the spectrum of all known oxidative phosphorylation d isorders and include MELAS, MERRF, Leigh syndrome, PEG, deafness, diabetes, sideroblastic anemia, myoclonus, skeletal myopathy, cardiomyopathy, and re nal tubular acidosis. Mutations in respiratory chain proteins encoded by mt DNA result in phenotypes ranging from exercise intolerance to blindness, at axia, dystonia, dementia, and Leigh syndrome. Conclusion The primary disorders of oxidative phosphorylation are commonly associated with a delayed age of onset, organ selectivity, and an episodic, progressive course. Organ-specific, non-ATP related functions of mitochond ria are discussed as important considerations in evaluating the pathogenesi s of mitochondrial disease.