Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 patients with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.
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PMID:Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias. 227 Jul 51

Leukocyte glutamate dehydrogenase (GDH) activity was measured in 11 healthy control subjects, 16 neurological controls, 12 patients with dominant late onset ataxia, 15 with sporadic late onset ataxia and 8 with alcoholic cerebellar ataxia. Serum hexosaminidase activity was also determined in ataxic patients. Concentrations of free amino acids were determined in the lumbal CSF of 16 neurological controls, 8 patients with late onset ataxia and 5 with alcoholic ataxia. Mean total GDH activity was reduced significantly in dominant (p less than 0.05) and sporadic (p less than 0.01) cerebellar ataxia, while the heat-labile form was decreased significantly (p less than 0.01) only in sporadic ataxia. All GDH activities were within normal range in patients with alcoholic ataxia. The serum hexosaminidase activities were also within reference range in all patient groups. The CSF concentrations of alanine, glycine, methionine and valine were significantly elevated and those of GABA and glutamate were normal in patients with late onset ataxia as compared to neurological controls. The most significant (p less than 0.01) increase was found for methionine. The amino acid levels of patients with alcoholic ataxia did not differ from those of the controls. The results suggest that GDH activity is only partially decreased in some ataxic patients and that altered amino acid metabolism may be reflected in the CSF.
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PMID:Leukocyte glutamate dehydrogenase and CSF amino acids in late onset ataxias. 228 45

A radioimmunoassay system for determining content of glutamate dehydrogenase (GDH) in human leukocytes was established and studied in 14 patients with spinocerebellar ataxia or atypical Parkinsonism. The protein content of leukocyte GDH was decreased in four patients and the reduction in the protein content was proportional to that in the enzyme activity. The ratio of GDH activity to protein content was invariable in healthy controls, diseased controls and patients with reduced GDH activity. These results suggested that at least a portion of the partial GDH deficiency was due to the decreased level of the enzyme protein.
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PMID:Decreased glutamate dehydrogenase protein in spinocerebellar degeneration. 321 8

Deficiency of glutamate dehydrogenase appears to be associated with a chronic progressive degenerative disorder manifesting parkinsonian extrapyramidal features, ataxia, supranuclear oculomotor dysfunction, a peripheral neuropathy and, in some cases, amyotrophy. The clinical features resemble those of the Dejerine-Thomas type of olivopontocerebellar atrophy. The data suggest autosomal dominant inheritance with low penetrance. Measurement of leukocyte glutamate dehydrogenase should be routinely performed in the evaluation of newly diagnosed or atypical cases of parkinsonism.
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PMID:Glutamate dehydrogenase deficiency in patients with olivopontocerebellar atrophy. 668 27

We measured the levels of three glutamate metabolizing enzymes, namely, glutamate dehydrogenase (GDH), aspartate aminotransferase (AAT), and glutamine synthetase (GS) in cerebellar and occipital cortices of nine patients with dominantly-inherited olivopontocerebellar atrophy (OPCA; spinocerebellar ataxia type I). As compared with the controls, mean GDH activities in cerebellar cortex of the OPCA patients were normal whereas levels of AAT (-17%) and the glial enzyme GS (-27%) were significantly reduced. No statistically significant changes were observed in occipital cortex, a morphologically unaffected brain area. We suggest that the decreased GS levels could reflect impaired capacity of astrocytes to metabolize glutamate which might contribute to the degenerative processes in OPCA cerebellum.
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PMID:Cerebellar glutamate metabolizing enzymes in spinocerebellar ataxia type I. 791 69

We studied the activity of glutamate dehydrogenase (GDH) in leukocytes from 23 patients with dominantly inherited ataxia. All the patients were assessed with a rating scale for ataxias and met the clinical criteria for the diagnosis of Machado-Joseph disease. The mean age of onset of symptoms was 37.8, SD 13.4 years and the duration of the disease was 7.4, SD 4.9. Leukocyte GDH activity was significantly decreased (p < 0.001) when compared to 20 normal controls. These data extend previous reports indicating that a GDH deficiency is present in peripheral tissues from some patients with spinocerebellar degenerations. Furthermore, this study suggests that a genetic deficiency of GDH may underlie some forms of dominant ataxias; this deficiency may be marked in patients with Machado-Joseph disease and is not specific for any type of multiple system atrophy.
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PMID:Glutamate dehydrogenase deficiency in Machado-Joseph disease. 833 77

A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.
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PMID:Autosomal dominant cerebellar ataxia deafness and narcolepsy. 874 54

In cattle with hepatic lipidosis, hepatic abscessation, leptospirosis, biliary calculi or fasciolosis, the progression of the disease was studied by serial measurements of serum total bile acid concentrations, plasma glutamate dehydrogenase, gamma-glutamyltransferase, 5'-nucleotidase and leucine aminopeptidase activities Terminalia avicennioides and by liver biopsy. Regardless of the cause of the hepatic disease, weight loss, anorexia, dullness and depression were consistent features. Signs of hepatic encephalopathy, such as blindness, head pressing, excitability, ataxia and weakness were less common and, together with pyrexia and jaundice, were grave prognostic signs. Plasma ammonia concentrations were significantly elevated compared to clinically normal cattle, but such changes were not always accompanied by a decline in plasma urea concentrations. In normal, healthy cattle, the plasma ammonia:urea concentration ratio is 9:1 and the plasma ammonia:glucose concentration is 11:1. In hepatic disease, a plasma ammonia:glucose ratio > 40:1 or plasma ammonia:urea ratio > 30:1, particularly with a rising total ketone body concentration and a declining glucose concentration, carried a guarded prognosis. The study suggested that other factors, such as hypokalaemia, alkalosis, short-chain volatile fatty acids, and false and true neuro-transmitters, may be important in the pathogenesis of hepatic coma in cattle.
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PMID:Clinical and pathological studies in cattle with hepatic disease. 909 45

Molecular biological studies confirmed that two glutamate dehydrogenase isozymes (hGDH1 and hGDH2) of distinct genetic origin are expressed in human tissues. hGDH1 is heat-stable and expressed widely, whereas hGDH2 is heat-labile and specific for neural and testicular tissues. A selective deficiency of hGDH2 has been reported in patients with spinocerebellar ataxia. We have identified an amino acid residue involved in the different thermal stability of human GDH isozymes. At 45 degrees C (pH 7.0), heat inactivation proceeded faster for hGDH2 (half life=45 min) than for hGDH1 (half-life=310 min) in the absence of allosteric regulators. Both hGDH1 and hGDH2, however, showed much slower heat inactivation processes in the presence of 1 mM ADP or 3 mM L-Leu. Virtually most of the enzyme activity remained up to 100 min at 45 degrees C after treatment with ADP and L-Leu in combination. In contrast to ADP and L-Leu, the thermal stabilities of the hGDH isozymes were not affected by addition of substrates or coenzymes. In human GDH isozymes, the 443 site is Arg in hGDH1 and Ser in hGDH2. Replacement of Ser by Arg at the 443 site by cassette mutagenesis abolished the heat lability of hGDH2 with a similar half-life of hGDH1. The mutagenesis at several other sites (L415M, A456G, and H470R) having differences in amino acid sequence between the two GDH isozymes did not show any change in the thermal stability. These results suggest that the Ser443 residue plays an important role in the different thermal stability of human GDH isozymes.
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PMID:Important role of Ser443 in different thermal stability of human glutamate dehydrogenase isozymes. 1504 2