Familial “mitochondrial” myopathy: A myopathy associated with disordered oxidative metabolism in muscle fibres Part 1. Clinical, electrophysiological and pathological findings

Abstract

Listen

Translate article

This report concerns a family, 6 members of which were known to have a progressive muscle disease, 5 of them with the pattern of muscle involvement regarded as diagnostic of facioscapulohumeral muscular dystrophy. Two other members were known to have muscle weakness of probably the same type. In addition 1 case was found with early signs of a proximal muscle weakness, and in 3 others the serum creatine kinase activity was raised; they were considered sub-clinical cases. The age of symptomatic onset ranged widely from 6 to 50 years, and the rate of progression was slow. Light microscopic study of skeletal muscle from 2 cases superficially showed a chronic myopathic picture with moderate continuing activity. Trichrome stains show the accumulation of granules in segments in many fibres. Histochemical studies showed a gross accumulation of mitochondrial activity in many fibres, while neutral lipid accumulation occurred less commonly. Ultrastructurally there was a wide range of mitochondrial change, ranging from abnormal mitochondria in otherwise normal fibres, to total replacement of a fibre with abnormal mitochondria. Many were huge, ranging up to 3 μ in diameter, with a variety of abnormality of cristae and paracrystalline “parking lot” inclusions. These changes were similar to those previously described in “mitochondrial” myopathies. Oxidative phosphorylation was poorly coupled in the mitochondria in the present family. A liver biopsy from 1 patient had numerous lipid droplets in the parenchymal cells but normal mitochondria. Several but not all the affected cases had grossly increased urinary excretion of taurine. Though similar mitochondrial changes have been reported in a variety of disorders of skeletal muscle, their extensive nature in this family, and their presence to a marked degree in the muscle of 1 sub-clinical case, prompted the conclusion that the mitochondrial abnormality was primary. The inheritance of the condition was compatible with an autosomal dominant mode, but only maternal line transmission was present. The possibility of cytoplasmic inheritance, in relationship to current concepts of mitochondrial origin and genetics, is discussed. The nosological position of facioscapulohumeral muscular dystrophy is also considered.