Multiple Symmetrical Lipomatosis--a mitochondrial disorder of brown fat.

Multiple Symmetrical Lipomatosis (MSL) is an unusual disorder characterized by the development of axial lipomas in adulthood. The pathoetiology of lipoma tissue in MSL remains unresolved. Seven patients with MSL were followed for a mean period of 12 years (8-20 years). All patients had cervical lipomas ranging from subtle lesions to disfiguring masses; six patients had peripheral neuropathy and five had proximal myopathy. Myoclonus, cerebellar ataxia and additional lipomas were variably present. All patients showed clinical progression. Muscle histopathology was consistent with mitochondrial disease. Five patients were positive for mtDNA point mutation m.8344A>G, three of whom underwent lipoma resection--all samples were positive for uncoupling protein-1 mRNA (unique to brown fat). Lipoma from one case stained positive for adipocyte fatty-acid protein-2 (unique to brown fat and immature adipocytes). This long-term study hallmarks the phenotypic heterogeneity of MSL's associated clinical features. The clinical, genetic and molecular findings substantiate the hypothesis that lipomas in MSL are due to a mitochondrial disorder of brown fat.

A locus for hereditary sensory neuropathy with cough and gastroesophageal reflux on chromosome 3p22-p24.

Hereditary sensory neuropathy type I (HSN I) is a group of dominantly inherited degenerative disorders of peripheral nerve in which sensory features are more prominent than motor involvement. We have described a new form of HSN I that is associated with cough and gastroesophageal reflux. To map the chromosomal location of the gene causing the disorder, a 10-cM genome screen was undertaken in a large Australian family. Two-point analysis showed linkage to chromosome 3p22-p24 (Zmax=3.51 at recombination fraction (theta) 0.0 for marker D3S2338). A second family with a similar phenotype shares a different disease haplotype but segregates at the same locus. Extended haplotype analysis has refined the region to a 3.42-cM interval, flanked by markers D3S2336 and D3S1266.

Myasthenia gravis: options and timing of immunomodulatory treatment.

The autoimmune pathogenesis of myasthenia gravis is relatively well understood. The current options for treatment of this disease are acute and long term immunotherapies, acetylcholinesterase inhibitors and thymectomy. Many factors influence the timing of initiation of immunomodulatory therapy in myasthenia gravis and both disease factors, such as stage and severity, and patient factors, such as age, pregnancy and intercurrent illness, must be considered. Decisions regarding the choice of therapy can be difficult because of the limited number of randomised controlled trials that have been performed in myasthenic patients. In general, acetylcholinesterase inhibitors alone are used only in mild ocular disease, and in the majority of other patients immunomodulatory therapy is begun early. Corticosteroids are the most commonly used initial therapy, followed by azathioprine. In refractory cases, the available options include immunosuppressants such as cyclosporin, mycophenolate mofetil and cyclophosphamide. Plasmapheresis and intravenous immunoglobulin are important in the treatment of acute exacerbations and myasthenic crisis and in the perioperative setting. Despite many years of experience, the role of thymectomy in improving long term outcome in nonthymomatous myasthenia gravis remains controversial.