[Clinical application of molecular diagnosis for mitochondrial encephalomyopathies]

Among various mitochondrial encephalomyopathies, there are three distinct clinical entities, including chronic progressive external ophthalmoplegia (CPEO), myoclonus epilepsy associated with ragged-red fibers (MERRF), and mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS). They are now clearly demonstrated to have the respective specific mitochondrial (mt) DNA mutations, which facilitate us to analyse mtDNA for practical diagnosis. With molecular analysis on 40 CPEO, 6 MERRF and 40 MELAS patients, most patients in the individual disorders had the disease-specific mutations. In CPEO, 31 of 40 patients had deleted mtDNA in a heteroplasmic distribution; the mutant mtDNA were present in a large amount in the skeletal muscle and other symptomatically affected organs as observed on Southern blotting and polymerase chain reaction (PCR). In MERRF (6 out of 6 patients) and MELAS (32 out of 40 patients), mutant mtDNA was easily detectable with PCR not only in skeletal muscle but also in blood cells from several patients examined. The results lead us to conclude that molecular analysis helps to obtain definite diagnosis of the diseases without loss of time.