DIAGNOSIS OF FATAL INFANTILE DEFECTS OF THE MITOCHONDRIAL RESPIRATORY-CHAIN - AGE-DEPENDENCE AND POSTMORTEM ANALYSIS OF ENZYME-ACTIVITIES

We studied two diagnostic aspects of fatal infantile defects of the mi tochondrial respiratory chain: the age dependence of muscle mitochondr ial enzyme activities and the reliability of diagnosis from autopsy sa mples. In morphologically normal quadriceps muscle samples of 46 child ren between the ages of 3 days and 15 years, activities of complex I p lus III (NADH:cytochrome c oxidoreductase) and complex II plus III (su ccinate:cytochrome c oxidoreductase) increased 2-fold during the first three years of life, while that of complex II (succinate dehydrogenas e), complex IV (cytochrome c oxidase), and citrate synthase did not sh ow significant correlation with age. We suggest that these changes are related to age and stress the importance of strictly age-matched cont rols when diagnosing a mitochondrial disease of early childhood. The v alue of autopsy samples in diagnostic studies was evaluated by compari ng mitochondrial enzyme activities in quadriceps muscle from autopsies and from surgical biopsies. In quadriceps muscle mitochondria, all th e enzyme activities studied remained stable for at least 3 h after dea th. Using age-matched controls and autopsy samples, we diagnosed a res piratory chain enzyme deficiency in two infants, and the defects were confirmed in cultured skin fibroblasts.