Mitochondrial activity in Pompe's disease

Mitochondrial oxidative metabolism was examined in two infants with Pompe's disease. The clinical diagnosis was confirmed by the demonstration of intr alysosomal glycogen accumulation and a deficiency of acid alpha-D-glucosida se in muscle biopsies. Light and electron microscopy studies demonstrated a normal number of mitochondria with normal ultrastructure, Spectrophotometr ic measurements revealed that the specific activities of citrate synthase a nd the partial reactions of electron transport were markedly elevated in th e skeletal muscle homogenates prepared from both infants with Pompe's disea se when calculated as micromoles per minute per gram wet weight of tissue. However, when respiratory chain enzyme activities were expressed relative t o citrate synthase as a marker mitochondrial enzyme, a different pattern em erged, in which all Pompe muscle respiratory enzymes, except complex IV, we re decreased relative to control subjects. These observations demonstrate t hat caution should be exercised when analyzing and interpreting data obtain ed from tissue homogenates in general and, in particular, in those prepared from tissues in which the wet weight of tissue may be altered, for example , by pathologic accumulation of carbohydrate or lipid. (C) 2000 by Elsevier Science Inc. All rights reserved.