A fatal, systemic mitochondrial disease with decreased mitochondrial enzyme activities, abnormal ultrastructure of the mitochondria and deficiency of heat shock protein 60.

We report on a girl presenting with facial dysmorphic features and breathing difficulties upon birth. She was hypotonic, developed a metabolic acidosis, and died two days old of heart failure. Post-mortem examination revealed abnormalities of brain, lungs, heart and liver. In cultured skin fibroblasts activities of enzymes of oxidative phosphorylation, pyruvate metabolism, beta-oxidation and other mitochondrial (mt) metabolic pathways were markedly decreased. Activities of enzymes localized in the mt outer membrane or in other cell organelles were found to be normal. The mitochondria appeared swollen and were located mainly around the nucleus. Electron micrographs showed locally disintegrated mt inner membranes and large mt vacuoles. The amount of mt heat shock protein 60 (hsp60) was about one fifth of that in controls. We conclude that this mt disorder is most likely caused by defective synthesis and maintenance of mitochondria, possibly due to a defect in mt protein import or enzyme assembly resulting from deficiency of hsp60.