31P NMR examination of two patients with NADH-CoQ reductase deficiency

Mitochondrial myopathies are becoming increasingly recognized as uncommon causes of muscular disorders1 characterized by weakness and severe exercise intolerance. Electron micrographs of the muscle show gross abnormality of the mitochondrial structure. Such defects are expected to affect the energy metabolism of muscle but investigations in human subjects have necessarily been limited by the need for biopsy material. Following extensive phosphorus nuclear magnetic resonance (31P NMR) measurements on isolated organs, tissues and selected parts of live animals (see ref. 2 for review), it has become possible to observe non-invasively the energy metabolism of human muscle in vivo3–5. Here, we report abnormal recovery of phosphocreatine (PCr) and pH after exercise of the forearm in two sisters, one of whom has been shown to have a mitochondrial NADH-coenzyme Q reductase deficiency and the other presumed to have the same defect on the basis of clinical symptoms, histology and biochemical studies of blood constituents6. Our results, together with studies on normal subjects and patients with impaired glycogen metabolism, allow the assessment of the relative importance of oxidative and glycolytic regeneration of high-energy phosphates during exercise and recovery.