Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0848771 (neurological disability)
 928 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In contradistinction to older populations, immune-mediated disorders (principally demyelinating processes) account for nearly half of peripheral neuropathies in childhood. The largest single diagnostic entity is GBS, which makes up approximately 25% of sensorimotor neuropathies in patients under 18 years of age. The clinical features are similar to those encountered in adults, although the prognosis in youngsters appears to be better than in older populations. Despite the absence of prospective data, plasmapheresis seems to be an effective modality for hastening recovery during GBS in children. The use of human immunoglobulin has gained acceptance for the treatment of GBS in adults, but insufficient data exist to draw firm conclusions about it role in the management of paediatric GBS. CIDP is the second most common cause of chronic sensorimotor neuropathy in children. The clinical manifestations of this disorder are extremely variable, and it can mimic the phenotype of several genetically determined neuropathies. The prognosis in this disorder is also relatively good, although a small number of children have significant neurological disability or treatment side-effects. Other immune-mediated neuropathies are relatively infrequent in our experience. When they occur, they are often associated with collagen-vascular diseases or bone marrow transplantation. Peripheral neuropathy in association with HIV infection in children appears to be rare.
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PMID:Immune neuropathies in childhood. 873 10

Hereditary motor and sensory neuropathy (HMSN) is one of the most frequently inherited causes of peripheral neurological disability. To date, the classification has been based on clinical, histological and genetic grounds. Due to increased genetic knowledge at the molecular level in recent years, diagnosis of the different subtypes has been considerably improved and their relationship clarified. We describe three generations of a family with HMSN IA (Charcot-Marie-Tooth disease IA = CMT 1A) with a genetic defect mapped to chromosome 17 and show the importance of genetic testing. Even in benign and clinically non-manifested causes of the disease, an early and non-invasive diagnosis should be made by genetic testing to identify affected persons; thus, nerve biopsy can be abandoned. Operations of pes cavus, which are not indicated and are often complicated by delayed healing, may be avoided. Instead, patients should undergo early physiotherapy and be counselled about their professional careers and family planning.
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PMID:[Charcot-Marie-Tooth syndrome. Clinico-genetic correlation in an affected family]. 885 Dec 97

Dysmyelination contributes to several human diseases including multiple sclerosis, Charcot-Marie-Tooth, leukodystrophies, and schizophrenia and can result in serious neurological disability. Properly formed, compacted myelin sheaths are required for appropriate nerve conduction velocities and the health and survival of neurons. Many different molecular mechanisms contribute to dysmyelination and many of these mechanisms originate at the level of the endoplasmic reticulum. The endoplasmic reticulum is a critical organelle for myelin biosynthesis and maintenance as the site of myelin protein folding quality control, Ca2+ homeostasis, cholesterol biosynthesis, and modulation of cellular stress. This review paper highlights the role of the endoplasmic reticulum and its resident molecules as an upstream and dynamic contributor to myelin and myelin pathologies.
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PMID:Endoplasmic reticulum quality control and dysmyelination. 2596 34

Highly specialized glial cells wrap axons with a multilayered myelin membrane in vertebrates. Myelin serves essential roles in the functioning of the nervous system. Axonal degeneration is the major cause of permanent neurological disability in primary myelin diseases. Many glycoproteins have been identified in myelin, and a lack of one myelin glycoprotein results in abnormal myelin structures in many cases. However, the roles of glycans on myelin glycoproteins remain poorly understood. Here, we report that sulfated N-glycans are involved in peripheral nervous system (PNS) myelination. PNS myelin glycoproteins contain highly abundant sulfated N-glycans. Major sulfated N-glycans were identified in both porcine and mouse PNS myelin, demonstrating that the 6-O-sulfation of N-acetylglucosamine (GlcNAc-6-O-sulfation) is highly conserved in PNS myelin between these species. P0 protein, the most abundant glycoprotein in PNS myelin and mutations in which at the glycosylation site cause Charcot-Marie-Tooth neuropathy, has abundant GlcNAc-6-O-sulfated N-glycans. Mice deficient in N-acetylglucosamine-6-O-sulfotransferase-1 (GlcNAc6ST-1) failed to synthesize sulfated N-glycans and exhibited abnormal myelination and axonal degeneration in the PNS. Taken together, this study demonstrates that GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfation of N-glycans on glycoproteins. These findings may provide novel insights into the pathogenesis of peripheral neuropathy.
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PMID:GlcNAc6ST-1 regulates sulfation of N-glycans and myelination in the peripheral nervous system. 2818 37