Skeletal muscle mitochondrial defects in nonspecific neurologic disorders

A group of 25 children (5 months to 20 years of age) presenting with intrac table seizures, developmental delay, and severe hypotonia, who did not fall into the Known categories of mitochondrial encephalomyopathies, underwent muscle biopsy for evaluation of mitochondrial function and were compared wi th age-matched control. subjects. Biopsied skeletal muscle was analyzed for six mitochondrial enzyme-specific activities, mitochondrial DNA point muta tions and deletions, and mitochondrial DNA levels. The data reveal a high i ncidence of specific mitochondrial enzyme activity defects, Reduced activit y levels were evident in complex I (11 patients), III (24 patients), IV (ni ne patients), and V (10 patients), Two patients also exhibited pronounced r eduction in mitochondrial DNA levels (80% reduction compared with control s ubjects). Two patients manifested increased levels of 5-kb11 and 7.4-kb mit ochondrial DNA deletions, Pathogenic mutations previously described in asso ciation with mitochondrial encephalomyopathies were not evident. The data s uggest that mitochondrial dysfunction, including extensive defects in speci fic enzyme activities, may be frequently present in children with seizures, developmental delay, and hypotonia that do not fall within the known mitoc hondrial encephalomyopathies. These mitochondrial deficiencies can be prima rily ascertained by biochemical analysis and are rarely accompanied by mito chondrial ultrastructural changes. The molecular basis of these defects, th eir role in these disorders, anal potential treatment warrant further study , (C) 1999 by Elsevier Science Inc, All rights reserved.