Hereditary metabolic myopathy with paroxysmal myoglobinuria due to abnormal glycolysis

Abstract

A myopathy with previously unknown characteristics is described. All of 14 patients belonging to 5 familes had experienced poor physical performance since childhood; 9 had passed dark urines and in 3 of these myoglobin was demonstrated spectrophotometrically. A relatively extensive examination of 8 of the patients showed poor physical performance, with even slight physical exertion producing exhaustion, dyspnea, tachycardia and hyperkinetic circulation; an abnormally high rate of blood flow in relationship to oxygen uptake; increased blood lactate and pyruvate levels in relation to work performed, thus suggesting abnormal glycolysis; abnormal electromyographic recordings following muscular exercise; and histological evidence of muscle fiber degeneration. Pathophysiologically the disorder is explained as muscle cell damage due to an accumulation of acid metabolites. The damage manifests itself in the form of muscle pain, hardness, tenderness, pareses and splitting of action potentials, as noted electromyographically. As cell damage increases myoglobin escapes into the blood stream and then into the urine. Myoglobinuria is a sign of advanced muscle destruction. The metabolic disorder in these cases is probably due to a defective gene which apparently follows a monohybrid autosomal recessive mode of inheritance.