PubMed · 11176932
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
J Phillips. 2001. Rethinking multiple sclerosis.. https://doi.org/10.1001/archneur.58.1.30
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
A group of 13 patients with early onset diaphragmatic palsy in association with a progressive neuropathy is presented. All eight of those tested were found to have mutations in the same gene encoding the immunoglobulin mu-binding protein 2 (IGHMBP2) in patients with spinal muscular atrophy (SMA) with respiratory distress type 1. Six out of these eight patients had either homozygous or compound heterozygous mutations, and two had only a single heterozygous mutation. Detailed analysis of the clinical picture and the neurophysiological and histopathological findings indicated that these patients shared similar characteristics, which were further developed as a set of diagnostic criteria. Some of the most striking of these were early onset of respiratory compromise, a markedly low birth weight, very slow motor nerve conduction velocities and a general decrease in the size of myelinated fibres on sural nerve biopsy. Extensive histological examination of the spinal cord in one patient failed to find any evidence of an SMA. Four out of the five not tested genetically were positive for all diagnostic criteria. None of the cases of early onset neuropathies or spinal muscular atrophies with early respiratory failure reviewed in the literature shares the exact characteristics, but many do have very close similarities. Their classification varies, but the discovery of mutations in IGHMBP2 in cases that are variously classified as SMA plus or severe infantile neuropathy with respiratory distress points to a need for the search for this genetic defect to be widened to include both groups. The fact that we identified other, similar cases of neuropathy and early respiratory failure with and without IGHMBP2 mutations suggests genetic as well as clinical heterogeneity in these infants. It is possible that infants that do not have mutations in the IGHMBP2 gene will be found to have mutations in a similar functioning gene.
The authors investigated whether T cells have a role in the pathogenesis of axonal polyneuropathy and monoclonal gammopathy by comparing the presence of T cells in sural nerves of 23 patients with axonal polyneuropathy and monoclonal gammopathy (12 IgM, 11 IgG), of 15 patients with chronic idiopathic axonal polyneuropathy, and of 10 autopsy cases. Seven patients with an increased T-cell density had a progressive disease course, and four of these patients were treated with prednisone with a good response, suggesting that vasculitis plays a role in the pathogenesis.
The ubiquitin-proteasome system regulates protein degradation in every eukaryotic cell. Recent work has shown that protein turnover mediated by the ubiquitin-proteasome system plays a key role in synaptic plasticity.