Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Abnormalities of GM2 ganglioside metabolism owing to hexosaminidase A (Hex A) deficiency have been associated with ALS phenotypes. The clinical features described in these ALS patients with Hex A deficiency include early onset, positive family history, and/or long disease duration. In an attempt to determine prospectively the incidence of Hex A deficiency within an ALS population, the records of The Mount Sinai Medical Center ALS Clinic were reviewed to select those patients with "atypical" ALS (total N = 52), i.e. onset before age 35, positive family history, and/or disease duration greater than 90 months. The control group (total N = 50), "typical" ALS patients, did not fulfill any of these historical criteria. Hex A activity determined in isolated peripheral blood leukocytes was normal in all typical ALS patients (mean 67.3%). Hex A deficiency was not found in any atypical ALS patients. Thus, Hex A deficiency apparently is an unusual etiology of typical or atypical ALS but is of medical and genetic importance in individual families.
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PMID:Hexosaminidase A activity and amyotrophic lateral sclerosis. 296

We studied three patients from two unrelated families with adult hexosaminidase A deficiency. A 30-year-old, non-Jewish proband in the first family had juvenile amyotrophic lateral sclerosis that evolved to mild dementia, ataxia, and axonal (neuronal) motor-sensory peripheral neuropathy. A 36-year-old Jewish proband in the second family had "pure" spinal muscular atrophy. One supposedly healthy brother of the first proband was found to have borderline IQ, mild spasticity, and ataxia but no evidence of motor neuron disease. Marked cerebellar atrophy was detected by head scans in all three patients. In both probands electromyograms were characterized by prominent, complex repetitive discharges in many muscles. Hexosaminidase A activities against the artificial substrate were similar to those reported in infantile Tay-Sachs disease; however, the hexosaminidase A level against GM2 substrates was higher than that found in infantile Tay-Sachs disease. The hexosaminidase A levels of the parents were in the heterozygous range. Motor neuron disease in our patients and in those previously described appears to be part of a multisystem degeneration of the nervous system.
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PMID:Motor neuron disease and adult hexosaminidase A deficiency in two families: evidence for multisystem degeneration. 315 34

In a search for evidence of biochemical disorders in regions of postmortem brain other than the motor cortex in amyotrophic lateral sclerosis (ALS), ganglioside patterns were also examined in the frontal, temporal, and parahippocampal gyrus cortex. In 21 ALS brains studied (20 sporadic, 1 familial), abnormal patterns were found in the frontal cortex (81%), temporal cortex (75%), motor cortex (70%), and parahippocampal gyrus cortex (71%). Patterns were established by measuring the percentage distribution of 12 ganglioside species. Two abnormal patterns were detected. One was based on low proportions of GD1b, GT1b, and GQ1b associated with high proportions of GM2 and GD3 (GM1, GD1a, GD2, and GT1a values were normal). The second abnormality was the appearance of Gx. Neither abnormality was seen in the 13 non-ALS control brains. The first, and predominant, abnormality was found in the frontal cortex in 14 brains, and the second was observed in 13 brains; 10 brains showed both abnormalities. These findings thus constitute evidence that the disease process in ALS extends beyond the motor cortex and involves neurons in several brain areas.
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PMID:Ganglioside patterns in amyotrophic lateral sclerosis brain regions. 403 52

Hexosaminidase deficiency diseases or GM2-gangliosidoses were originally described as infantile encephalopathies. Recently, hexosaminidase deficiencies have been found with different phenotypes, including juvenile and adult encephalopathies, cerebellar ataxias, and motor neuron diseases. Individual cases have resembled Ramsey-Hunt syndrome, olivopontocerebellar ataxia, Friedreich ataxia, amyotrophic lateral sclerosis, Kugelberg-Welander disease, Fazio-Londe disease, and Charcot-Marie-Tooth disease. Tremor, dystonia, spastic paresis, and psychosis have been seen. Since few diagnosable causes for these system atrophies are known, these patients should be tested for hexosaminidase deficiency. These recessive disorders fit a multiple loci/multiple alleles genetic scheme, and a clinical genetic classification is presented.
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PMID:The clinical spectrum of hexosaminidase deficiency diseases. 719 92

We have examined ganglioside compositions and the presence of sulfated glucuronyl glycolipids of immortalized motor neuron-like cell lines, neuroblastoma-spinal cord (NSC) hybrid cell lines established by fusing mouse neuroblastoma N18TG2 with motor neuron-enriched embryonic spinal cord cells. Among NSC cell lines, only NSC-34 aggregates acetylcholine receptors on co-cultured myotube and expresses a receptor for S-laminin, a neuromuscular junction specific basal lamina protein. GM2, which is only a minor ganglioside component of CNS, was the major component in NSC-34 occupying almost 75% of total gangliosides, whereas GD1a and GM3 were major species in the parental N18TG2, which had only 8.5% GM2. These results indicated that NSC lines have unique ganglioside pattern that is distinctive from other nervous tissues, and this pattern, especially that of NSC-34 cells, might reflect the characteristics of mouse spinal motor neuron gangliosides. Sulfated glucuronyl paragloboside was demonstrated to be present in N18TG2, however, it could not be detected in either of NSC cell lines. Even though the pathogenesis of amyotrophic lateral sclerosis remains unknown, autoimmunological participation has been suggested. Because high-titered antibody against GM2 has been observed in a patient with amyotrophic lateral sclerosis-like disease, GM2 which is possibly expressed on the surface of motor neurons might serve as a potential target antigen in this disorder.
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PMID:Ganglioside characterization of a cell line displaying motor neuron-like phenotype: GM2 as a possible major ganglioside in motor neurons. 759 35

Paired cerebrospinal fluid and serum samples of patients with amyotrophic lateral sclerosis (n = 35) revealed no consistent abnormalities of CSF cell count, CSF albumin, CSF IgG, CSF IgM, IgG or IgM index, or oligoclonal immunoglobulin band formation in the CSF. Determination of IgG and IgM CSF and serum antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b, and GT1b showed a characteristic pattern which allowed the differentiation of amyotrophic lateral sclerosis from controls and from patients with other neurological disorders including multiple sclerosis. Specifically, patients with the disease had elevated CSF IgM antibodies to all gangliosides except AGM1. The lack of correlation between the CSF findings and corresponding serum antibodies suggests a chronic, compartmental, intrathecal immune response of low activity in amyotrophic lateral sclerosis. Whether this immune response is primary and of pathogenetic significance, or an epiphenomenon of neuronal degeneration, remains to be investigated.
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PMID:A characteristic ganglioside antibody pattern in the CSF of patients with amyotrophic lateral sclerosis. 773 82

A motor neuron disorder resembling that of amyotrophic lateral sclerosis was found in a patient who had received the intramuscular administration of a mixture of bovine brain gangliosides (Yuki, N., Sato, S., Miyatake, T., Sugiyama, K., Katagiri, T., and Sasaki, H. (1991) Lancet 337, 1109-1110). A very high titer of anti-GM2 IgM was detected in the patient's serum and the patient quickly recovered after plasmapheresis. The clinical course of the patient appeared to be different from amyotrophic lateral sclerosis and the anti-GM2 IgM was thought to be the culprit. The IgM reacted with GM2, GM1b-GalNAc, SPG(alpha 2-3)-GalNAc, and GD1a-GalNAc, but not with GA2 or GD2, meaning that the epitope recognized by the IgM was the GM2-like terminal structure, GalNAc beta 1-4(Neu-Ac alpha 2-3)Gal beta 1-. In this study, we found two novel GM2-epitope containing gangliosides, X1 and X2, in bovine brain gangliosides by TLC immunostaining using the patient's IgM. They were characterized as unique lacto-ganglio type gangliosides containing the following branching structures. [formula: see text] Their unusual structures may be immunogenic to humans to induce anti-GM2 antibody.
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PMID:Novel lacto-ganglio type gangliosides with GM2-epitope in bovine brain which react with IgM from a patient of the amyotrophic lateral sclerosis-like disorder. 769 4

To limit genetic heterogeneity, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenic and autistic probands, to determine if similar causal mechanisms might obtain for both conditions. At least two previous epidemiological studies have demonstrated increased risk for schizophrenia in Ashkenazi Jews. The hypothesis posed is that increased prevalence of various rare autosomal recessive diseases among the Ashkenazim might contribute to the increased vulnerability to schizophrenia and to autism in this large genetic isolate. Rates of amyotrophic lateral sclerosis (ALS) and bleeding disorders were significantly increased among relatives of schizophrenic and autistic probands, compared to relatives of normal probands. These results suggest new candidate loci in schizophrenia and autism, particularly the chromosome 15q23-24 locus of the hexosaminidase A gene, causing various GM2 gangliosidoses, and the 21q22.1-q22.2 loci of the antioxidant, superoxide dismutase gene, and a cytokine receptor gene.
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PMID:A family history study of schizophrenia spectrum disorders suggests new candidate genes in schizophrenia and autism. 783 15

We report a case of amyotrophic lateral sclerosis (ALS) with IgM antibody against gangliosides GM2 and GD2. A 57-year-old woman presented with slowly progressive muscular weakness of the upper extremities and dysarthria. She fulfilled the clinical and electrophysiological criteria of ALS, and died from sudden suffocation about 3 years after the onset of illness. The patient's serum IgM antibody was shown to recognize the structure shared by GM2 and GD2. Since anti-GM2 antibodies have been implicated in motor neuropathy or motor neuron syndrome, this rare case might contribute to the understanding of the immunological aspects of ALS.
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PMID:Amyotrophic lateral sclerosis with IgM antibody against gangliosides GM2 and GD2. 1270 85

The hybrid ganglioside X1, which was identified in the bovine brain, was synthesized for the first time. Ganglioside X1 is believed to be involved in the development of amyotrophic lateral sclerosis-like disorders in patients with neurological disorders after treatment with bovine brain gangliosides. A convergent approach using two branched glycan units, the GM2-core trisaccharide and the lacto-ganglio tetrasaccharide, efficiently provided the highly branched heptasaccharide part of ganglioside X1, which was conjugated with the ceramide part to produce the protected ganglioside X1. Global deprotection delivered homogenous ganglioside X1, with which serum from the patient was reacted.
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PMID:A first total synthesis of a hybrid-type ganglioside associated with amyotrophic lateral sclerosis-like disorder. 2120 77


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