Myopathy with mitochondrial alterations in patients with primary biliary cirrhosis and antimitochondrial antibodies

Objective. To describe a syndrome of severe progressive myopathy, cardiomyopathy, and gastrointestinal dysmotility in 2 patients with asymptomatic primary biliary cirrhosis (PBC) and circulating anti‐mitochondrial autoantibodies, and to review pertinent literature concerning this syndrome. Methods. Clinical, electrophysiologic, serologic, and pathologic studies of the 2 affected patients were conducted. Results. Skeletal muscle involvement was manifested by progressive weakness of the proximal muscles, marked diaphragmatic dysfunction with consequent hypoventilation and respiratory failure, and moderately elevated levels of muscle‐associated enzymes. Serum from both patients contained antimitochondrial antibodies that reacted with components of the mitochondrial keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastructural changes in the skeletal muscles were distinct from those of typical myositis, and were notable for striking subsarcolemmal aggregation of abnormal mitochondria in the absence of significant inflammation. Conclusion. Severe skeletal muscle, cardiac, and gastrointestinal pathology with abnormalities of the muscle mitochondria develops in a subset of patients with mild PBC and antimitochondrial antibodies. The pathogenesis of this syndrome is unclear, but may be related to the presence of the antimitochondrial autoantibodies.