Multiple Symmetric Lipomatosis: Evidence for Mitochondrial Dysfunction

Objectives: To assess the presence of mitochondrial dysfunction in 18 patients with multiple symmetric lipomatosis (MSL). Methods: Electromyography and nerve conduction study were performed in 15 patients with MSL and autonomic tests in 14. Nerve biopsy was done in four patients and muscle biopsy in six. Mitochondrial enzyme activities were measured in six muscle biopsies. We investigated myoclonic epilepsy ragged red fibers (MERRF) point mutation and multiple deletions in mtDNA with PCR, enzyme restriction digestion, and Southern blot analysis in lymphocyte DNA, or in muscle DNA when available. Results: Clinical or electrophysiological signs of polyneuropathy were found in 12 patients. Peroneal nerve biopsy showed decreased myelinated fibers. In muscle biopsies there were hyporeactive areas and subsarcolemmal rims of mitochondria. Respiratory chain enzymes levels showed a significant decrease of cytochrome-c oxidase (COX), succinic dehydrogenase (SDH), and citrate synthetase activity. Lymphocyte mtDNA showed the MERRF point-mutation in only one patient with MSL. Conclusions: The mitochondrial dysfunction in MSL seems to be consistent with a reduced number of mitochondria and reduced mitochondrial enzyme activities; this could represent the pathogenetic basis of lipoma formation, as well as of other multisystemic clinical manifestations.