Myopathy with abnormal structure and function of muscle mitochondria.

When the rate of respiration of mitochrondria in the presence of inorganic phosphate cannot be increased by adding adenosine diphosphate (A.D.P.) but these particles can still couple respiration to phosphorylation of A.D.P. to adenosine triphosphate (A.T.P.), the state of respiration is called 'loosely coupled'. The first patient in whom such a loosely coupled state of oxidative phosphorylation of the muscle mitochrondria was found was described by Ernster, Ikkos, and Luft (1959). The patient suffered from generalized myopathy with progressive asthenia and severe hypermetabolism. The structure of the muscle mitochondria was markedly altered as shown by electron microscopy (Luft, Ikkos, Palmieri, Ernster, and Afzelius, 1962). The second patient with the same biochemical disturbance of oxidative phosphorylation of the muscle mitochondria was described by Van Wijngaarden, Bethlem, Meijer, Hiilsmann, and Feltkamp (1967). This patient showed a proximal myopathy without hypermetabolism. Histological examination of a muscle biopsy revealed subsarcolemmal zones that contained small granules. In these zones, an increased activity of oxidative enzymes was demonstrated. Electronmicroscopic examination showed the presence of pathological mitochondria. Large spherical, rod-shaped or annular mitochondria were observed. The morphology of the pathological mitochondria differed in many respects from that observed by Luft et al. (1962), who, in addition, found peculiar inclusions in the mitochondria. Giant mitochondria with rectangular and other inclusions were found in the muscle of a child with proximal weakness by Shy, Gonatas, and Perez (1966), in a disorder which they termed megaconial myopathy. In this case, data on biochemical studies of oxidative phosphorylation of the morphologically altered muscle mitochondria were not given.