Severe Hypermetabolism with Primary Abnormality of Skeletal Muscle Mitochondria

Abstract

A 19-year-old woman with features of extreme hypermetabolism, believed to have the second reported case of Luft's syndrome, was studied. The clinical manifestations almost duplicate those reported by Luft. Electron-micrographic and biochemical data indicate that the immediate factor responsible is a large overgrowth of skeletal muscle mitochondria, anatomically bizarre and functionally characterized by excessive respiration and uncoupling of oxidative phosphorylation. A defective protein content or structure of mitochondria may be responsible for most of the functional defects. Chloramphenicol produced clinical improvement, apparently largely as a result of depression of synthesis of abnormal mitochondria. All findings are best explained by the concomitant operation in skeletal muscle of a pseudoneoplastic, uncoupled, increased mass of abnormal mitochondria and a reduced mass of mitochondria functioning normally. Chloramphenicol has a differential effect on the former. Certain differences between the "coupling" data of Luft and ours and certain aspects of the "coupling" response to chloramphenicol remain unexplained, as does the ultimate etiology of the mitochondrial disease.