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

The phosphomannosyl receptor system is responsible for both the receptor-mediated endocytosis and the intracellular transport of lysosomal enzymes. In the present study this receptor system was examined in affected muscles of patients with various neuromuscular diseases. The total activity of beta-N-acetyl-glucosaminidase, a marker enzyme of lysosomal hydrolases, was significantly elevated in the patients with myopathies (polymyositis and muscular dystrophies) but only slightly increased in those with neurogenic muscle atrophies (amyotrophic lateral sclerosis, polyneuropathy or other neurogenic muscle disease). The increase was most prominent in the group of polymyositis. The content of phosphomannosyl receptors was increased in the patients with myogenic muscle disease but not in those with neurogenic disease. The receptor binding of lysosomal enzymes was saturable and inhibited with mannose 6-phosphate showing the typical characteristics of phosphomannosyl receptors. The characteristics of the receptors were very similar both to control and to diseased muscle samples. When surveying all the material, the content of phosphomannosyl receptors correlated highly significantly with the muscular activity of beta-N-acetylglucosaminidase, muscle atrophy index, and serum creatine kinase activity.
 ...
PMID:Phosphomannosyl receptors of lysosomal enzymes of skeletal muscle in neuromuscular diseases. 284 20

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.
 ...
PMID:Hexosaminidase A activity and amyotrophic lateral sclerosis. 296

The cause of amyotrophic lateral sclerosis is not known. However, there is increasing evidence that the syndrome has more than one cause. Many of the different categories of causation are dealt with in the papers presented in this symposium - including genetic and acquired forms, and multiple categories within those two major classes. The diversity of different causes gives hope that progress in one field will be followed by elucidation of other fields. As examples, there has been progress in understanding the genetic forms due to hexosaminidase deficiency and molecular genetics is being applied to other heritable motor neuron diseases. Among acquired diseases, in different parts of the world, there has been new evidence that persistent viral infection may be important, that dietary constituents may be important, and that paraproteinemia may be important.
 ...
PMID:Research progress in motor neuron diseases. 306 74

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.
 ...
PMID:Motor neuron disease and adult hexosaminidase A deficiency in two families: evidence for multisystem degeneration. 315 34

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.
 ...
PMID:The clinical spectrum of hexosaminidase deficiency diseases. 719 92

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.
 ...
PMID:A family history study of schizophrenia spectrum disorders suggests new candidate genes in schizophrenia and autism. 783 15

To limit the genetic heterogeneity of schizophrenia, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenia probands. The hypothesis posed is that the increased prevalence among the Ashkenazim of the rare lysosomal enzyme disorders, Tay Sachs disease (TDS), caused by low levels of hexosaminidase A, and Gaucher's disease (GD), caused by low levels of glucocerebrosidase, might contribute to the demonstrated increased vulnerability to schizophrenia in this ethnic group. Signs and symptoms characterizing the candidate illnesses were systematically queried by the family history method. Rates and relative risks for symptoms characterizing these disorders and for several nonautosomal illnesses associated with TSD and/or GD (i.e., amyotrophic lateral sclerosis and Hodgkin's disease, leukemia and lymphoma) are significantly elevated in the schizophrenia pedigrees, compared to controls. The conditions with elevated rates and risks have been associated with chromosomal regions 1q21 and 15q23-q24. These areas are suggested as candidate regions for future targeted deoxyribonucleic acid (DNA) research in schizophrenia.
 ...
PMID:Medical conditions in Ashkenazi schizophrenic pedigrees. 797 67

A 35-year old Japanese male with adult Sandhoff disease was described, who was presented as a motor neuron disease phenotype with slow progression. At the age of 15, he first noticed weakness in his thigh. At the age of 28, his upper and lower motor neuron disturbances were disclosed. He was diagnosed as atypical amyotrophic lateral sclerosis. At the age of 34, a slight sensory disturbance appeared in the lower extremities. When he was admitted to our hospital, he displayed marked atrophy and weakness in his quadriceps femoris muscles, but no signs of mental deterioration and cerebellar ataxia. Because of the atypical course of motor neuron disease, hexosaminidase activity in peripheral leukocytes was determined. The assay of total hexosaminidase, hexosaminidase A and hexosaminidase B activities demonstrated low levels of these activities (7-15% of controls), leading the diagnosis of Sandoff disease. He was a member of non-consanguineous family, and the abnormal patterns of hexasaminidase activities were different between his father and mother. These data appear to show that he is a compound heterozygote in the locus of the hexosaminidase B gene. This is the first Japanese case of adult Sanhoff disease presented as a motor neuron disease phenotype.
 ...
PMID:[Adult Sandhoff disease presented as a motor neuron disease phenotype with slow progression]. 1143 65

Patients with adult hexosaminidase A (Hex A) deficiency may have clinical manifestations similar to amyotrophic lateral sclerosis (ALS). Mutations in the hexosaminidase A (HEXA) gene are common in the Jewish Ashkenazi population in Israel. Serum samples of 115 Israeli patients with sporadic ALS were screened for enzymatic activity to detect "enzyme-based carriers." Fifteen samples with low (< 50%) enzymatic activity were subjected to mutation analysis, which included the two common mutations in the HEXA gene among Ashkenazi Jews (+1278TATC and IVS12+1G-->C). Three "enzymatic carrier" patients of Moroccan origin were checked for two additional mutations (DeltaF304/305 and Arg170-->Gln), specific to this ethnic group. Two "enzymatic carrier" patients of Iraqi origin were analyzed for the mutation Gly250-->Val, specific to this population. The mutation Gly 269-->Ser was screened in carriers of Ashkenazi origin only (n = 10). The only abnormalities found were heterozygous +1278TATC mutations in two Ashkenazi patients. Their clinical presentation was not different from that usually encountered in ALS. The frequency of mutations in the HEXA gene among Israeli ALS patients was not higher than in the healthy Israeli population. Therefore, Hex A deficiency seems to be a very unlikely cause of an ALS-mimic syndrome.
 ...
PMID:Hexosaminidase A deficiency is an uncommon cause of a syndrome mimicking amyotrophic lateral sclerosis. 1281 81

Here, we report a Japanese man with adult Sandhoff disease who presented with a motor neuron disease phenotype with slow progression. At the age of 42, he noticed weakness in his legs. At the age of 46, he was admitted to our hospital. Neurological examination revealed muscle weakness and atrophy of the upper and lower extremities, and hyperreflexia of the upper extremities. Magnetic resonance imaging showed very mild cerebellar atrophy. We diagnosed him as having atypical amyotrophic lateral sclerosis. Because of the atypical course of motor neuron disease, hexosaminidase activity in peripheral leukocytes was indicated. Asseys of hexosaminidase A and hexosaminidase B showed low activities, and we found a membranous cytoplasmic body in the submucosal nerve, leading to the diagnosis of Sandhoff disease. This is the second case of a Japanese adult with Sandhoff disease presenting with a motor neuron disease phenotype, and to our knowledge, this is the latest age of onset in Japan.
 ...
PMID:[A patient with GM2 gangliosidosis presenting with motor neuron disease symptom in his forties]. 1749 35


1 2 Next >>