Myopathy caused by a deficiency of Ca 2+ ‐adenosine triphosphatase in sarcoplasmic reticulum (Brody's disease)

Four male patients from two families were first seen with impaired skeletal muscle relaxation that rapidly worsened during exercise. Muscle biopsies from 2 patients were examined by appropriate biochemical and microscopic immunocytochemical techniques. The adenosine triphosphate (ATP)–dependent Ca 2+ transport rate was extremely low in a particulate membrane fraction of skeletal muscle, and there was also a marked reduction of the concentration of 100‐kD phosphoprotein, corresponding to Ca 2+ ‐ATPase of sarcoplasmic reticulum, in muscle microsomes. The concentration of immunoreactive Ca 2+ ‐ATPase of sarcoplasmic reticulum was markedly reduced on immunoblots. Evaluation by microscopic immunocytochemical techniques, using one polyclonal and two monoclonal antibodies against sarcoplasmic reticulum Ca 2+ transport protein, revealed that the severe reduction of immunoreactive Ca 2+ ‐ATPase was limited to the histochemical type 2 fibers. The deficiency of the Ca 2+ transport protein in the sarcoplasmic reticulum of type 2 fibers, which may be the primary expression of a presumed gene defect, can explain the impaired muscle relaxation of the patients. This disease appears to be a clinically, electromyographically, and biochemically distinct metabolic myopathy.