MYOPATHY WITH MITOCHONDRIAL ALTERATIONS IN PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS AND ANTIMITOCHONDRIAL ANTIBODIES

Objective. To describe a syndrome of severe progressive myopathy, card iomyopathy, and gastrointestinal dysmotility in 2 patients with asympt omatic primary biliary cirrhosis (PBC) and circulating antimitochondri al autoantibodies, and to review pertinent literature concerning this syndrome. Methods. Clinical, electrophysiologic, serologic, and pathol ogic studies of the 2 affected patients were conducted. Results. Skele tal muscle involvement was manifested by progressive weakness of the p roximal muscles, marked diaphragmatic dysfunction with consequent hypo ventilation and respiratory failure, and moderately elevated levels of muscle-associated enzymes. Serum from both patients contained antimit ochondrial antibodies that reacted with components of the mitochondria l keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastr uctural changes in the skeletal muscles were distinct from those of ty pical myositis, and were notable for striking subsarcolemmal aggregati on of abnormal mitochondria in the absence of significant inflammation . Conclusion. Severe skeletal muscle, cardiac, and gastrointestinal pa thology with abnormalities of the muscle mitochondria develops in a su bset of patients with mild PBC and antimitochondrial antibodies. The p athogenesis of this syndrome is unclear, but may be related to the pre sence of the antimitochondrial autoantibodies.