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Alastair Compston, A mitochondrial myopathy characterised by a deficiency in reducible cytochrome b. By JA Morgan-Hughes, P Darveniza, SN Kahn, DN Langdon, RM Sherratt, JM Land and JB Clark (From the Institute of Neurology, Queen Square, London WC1 and the Biochemistry Department, St Bartholomew's Hospital Medical College, London EC1) Brain 1977; 100: 617–640., Brain, Volume 131, Issue 11, November 2008, Pages 2805–2808, https://doi.org/10.1093/brain/awn286
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Hitherto, morphological changes seen in mitochondria obtained from samples of skeletal muscle in a variety of neuromuscular disorders have not been correlated with functional abnormalities and so have not been considered significant for the pathogenesis of these conditions. But more recently, investigators from Cornell University have linked these same ultrastructural features to a primary biochemical abnormality of mitochondrial function. The evidence hints at a disturbance of cellular respiration in the presence of various substrates. In Luft's disease, hyper-metabolism (not of thyroid origin) is observed but, for the rest, insights into the disease mechanisms are lacking. Now that situation changes. ‘The present paper reports the findings in a man whose weakness and striking muscular fatigability appeared to be due to a primary disturbance of mitochondrial function. Biochemical studies of isolated mitochondrial fractions have shown a specific deficiency of reducible cytochrome b’.
N.T., now aged 38 years, has had weakness and muscle fatigue since early childhood and has not been able to run or play games from his mid-teens. Nor was he able to continue his apprenticeship as a tailor through inability to work the foot-operated treadle of a sewing machine. Later, some bulbar symptoms emerged. Cold and alcohol seem to make him worse. On examination, he is short in stature with normal appearing if somewhat wasted muscles but showing weakness of the face (sparing the eyelids and eye movements), neck, and shoulder and pelvic girdles. The tendon reflexes are absent in the legs. ‘The most striking abnormality was a marked and progressive increase in muscle weakness during sustained activity … or repetitive manoeuvres … after a few minutes of complete rest, muscle strength returned to its pre-exercise level’. Screening investigations show only an excess of urinary lactate and pyruvate. Routine electromyography is equally unremarkable although his ability to exert maximal voluntary force at the elbow is reduced to 5.5 kg; and motor and sensory nerve conduction studies are also normal. Against this background, neurophysiological tests are carried out of electrical and mechanical responses to repetitive stimulation of the abductor digiti minimus and anterior tibial group, each constrained in a suitable jig for studying isometric responses to varying degrees of resistance, at rates that do not lead to fusion of the twitch responses, and before and after sustained voluntary muscle activity. Control observations on oxygen consumption and electrophysiology are made in ‘a healthy male subject’ (P.D.).
