MULTIPLE SYMMETRICAL LIPOMATOSIS - ABNORMALITIES IN COMPLEX-IV AND MULTIPLE DELETIONS IN MITOCHONDRIAL-DNA

Multiple symmetric lipomatosis (MSL) is a rare disorder of middle life characterized by large nonencapsulated lipomas distributed around the neck, shoulders, and other axial regions. Neurologic involvement, par ticularly peripheral neuropathy, is frequent. The pathogenesis of the syndrome is still unknown, but ragged-red fibers are occasionally pres ent in muscle of affected patients, suggesting a mitochondrial abnorma lity. We studied 11 unrelated patients with MSL by means of neurophysi ology, muscle morphology, muscle biochemistry, Southern blot, and PCR analysis of mitochondrial DNA. All patients were men aged 41 to 63 yea rs. Clinical or electrophysiologic signs of a sensorimotor polyneuropa thy were present in nine patients, eight of whom had a history of alco holism. In muscle biopsy specimens, the most prominent feature was pat hologic subsarcolemmal aggregates of mitochondria. Biochemical analysi s of respiratory chain enzymes revealed a moderate but significant dec rease of cytochrome c oxidase activity as compared with age-matched co ntrols. In one patient, Southern blot analysis showed multiple deletio ns of mitochondrial DNA. We conclude that mitochondrial dysfunction is common in MSL and may be based on identifiable defects in the mitocho ndrial genome.