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)

Phase three of the Quebec Cooperative Study of Friedreich's Ataxia was devoted to an understanding of the physiopathology of individual symptoms on the basis of previously discovered biochemical leads. The present paper attempts to pull these results together by presenting, as a hypothesis, a unifying scheme of possible interactions and relationships. The central core of this hypothesis is the demonstration in Friedreich's ataxia of a state of mitochondrial energy deprivation. This is indirectly responsible for such associated and important symptoms as muscle weakness, dying-back neuropathy, scoliosis and hypertrophic cardiomyopathy. Secondarily, and possibly as an independent but linked-event, the entry of glucose into cells and pyruvate oxidation, are slowed down, favoring the development of diabetes. As a consequence, tissue concentrations of glutamic acid and aspartic acid are decreased, particularly in more vulnerable areas such as the cerebellum, brain stem and dorsal root ganglia. This tissue deficiency in putative excitatory neurotransmitters is directly responsible for the symptom of ataxia. This conclusion is reinforced by the correction of the ataxia in experimental animals, by the intraventricular injection of the same amino acids, and not by the injection of other stimulants of motricity. The observed mitochondrial energy deprivation could be the metabolic consequence of major changes in the linoleic acid (18.2) composition of inner mitochondrial membrane phospholipids, such as cardiolipin. Such decreases in membrane 18:2 could be the result of interference with the normal incorporation of this fatty acid to lipoproteins and/or cell membranes. It is at this level that the search for the specific enzyme defect in Friedreich's ataxia is continuing.
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PMID:Friedreich's ataxia 1980. An overview of the physiopathology. 678 90

Pyruvate dehydrogenase complex (PDHC) activity was measured in cultured fibroblasts from 12 patients with Friedreich's ataxia (FA), and in 1 patient with lactic acidosis and ataxia. The activities obtained after extraction of PDHC by different methods were compared. Triton-X-100 extraction yielded enzyme activities 5 to 10 times greater than those obtained with the older methods. With this sensitive technique, PDHC activity was markedly deficient in fibroblasts from the patient with lactic acidosis and ataxia but it was normal in the fibroblasts from FA patients. Mg++ activation of the PDHC in FA fibroblasts was normal.
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PMID:Pyruvate-dehydrogenase complex in ataxic patients: enzyme deficiency in ataxic encephalopathy plus lactic acidosis and normal activity in Friedreich ataxia. 682 14

Visual (VEP), brainstem auditory (BAEP), and somatosensory (SEP) evoked potential tests were performed in 45 patients representing ten types of inherited disorders in which ataxia was the most prominent symptom. Comparable VEP abnormalities were present among all types of patients. Normal BAEP tests were recorded in most patients except those with olivopontocerebellar atrophy. SEP results were often more severely abnormal in patients with Friedreich's ataxia. The observations emphasize the similarity in expression of different metabolic-degenerative disorders. When these tests are used clinically, certain features of evoked potentials (especially left-right symmetry) are typical of the inherited ataxias as a group. Few distinguishing features differentiate the individual disorders.
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PMID:Evoked potential abnormalities in the various inherited ataxias. 683 Jan 60

A case of Friedreich's ataxia of the spine with intranuclear bodies in the cerebrum and stem was found in a 43-years old man. The disease is possibly the result of measles contracted when the patient was seven. This is the first observation of this type known to us; Friedreich's spinal ataxia has until now been believed to exist only hereditary ("hereditary spinal ataxia").
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PMID:[Friedreich's spinal ataxia following measles? Overview of central nervous system diseases caused by measles - (preliminary report)]. 688 51

This study extends previous observations of pyruvate metabolism in the spino-cerebellar degenerations by screening for abnormalities of pyruvate oxidation using the rise in blood pyruvate after an oral glucose load and examining the activity of the lipoamide dehydrogenase (LAD) moeity of the pyruvate dehydrogenase complex in the serum of 31 patients with Friedreich's ataxia, hereditary spastic ataxia and primary cerebellar degeneration. Serum LAD activity was significantly reduced in 10 Friedreich's ataxia patients when compared to controls and to 10 patients with spastic ataxia, thus confirming previous studies. Two patients with Friedreich's ataxia and 2 with primary cerebellar degeneration had abnormal blood pyruvate curves after oral glucose loading. The findings suggest that abnormal pyruvate oxidation occurs in some cases of Friedreich's ataxia and primary cerebellar degeneration and that the abnormality of pyruvate metabolism is not necessarily reflected in the serum LAD activity of these patients. The relevance of these findings to the heterogeneity of the hereditary ataxias is discussed.
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PMID:An investigation of pyruvate metabolism in patients with cerebellar and spinocerebellar degeneration. 689 66

The activity of lipoamide dehydrogenase was abnormally heat-labile in homogenized platelets from seven patients with as recessive ataxia conforming to the syndrome of Friedreich ataxia or clinical variants. Taken together, the abnormality and previous findings of low activity and abnormal kinetic properties are compatible with a change in the conformation of the enzyme in these patients.
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PMID:Lipoamide dehydrogenase: rapid heat inactivation in platelets of patients with recessively inherited ataxia. 689 19

Cranial computerized tomography was carried out in 110 patients with cerebellar ataxia [53 with Friedreich's ataxia, 4 with Marie's spastic ataxia, 51 with cerebellar atrophy, and 2 patients with olivopontocerebellar atrophy). In CT scans, cerebellar atrophies are found to be of various localization and partially of characteristic distribution. CT, therefore, greatly helps to distinguish different types of cerebellar and spinocerebellar atrophies and allows the differentiation of cerebellar atrophies of various origins from other diseases, such as multiple sclerosis.
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PMID:Cranial computerized tomography in spinocerebellar atrophies. 695 61

Computed tomographical findings are documented for 140 patients with different cerebellar atrophic or heredodegenerative processes. There are idiopathic cerebellar atrophies, so called alcoholic and paraneoplastic cerebellar atrophies, cerebellar atrophies associated with nutritional deficiency diseases or intake of diphenylhydantoin. Further, there are patients suffering from Friedreich's ataxia. Nonne-Marie's spastic ataxia, olivo-ponto-cerebellar atrophy and various other diseases. With the aid of CT individual patterns of atrophy can be recognized. The method therefore, helps to distinguish the above mentioned diseases from each other and also distinguishes them from inflammatory, cerebrovascular or neoplastic processes.
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PMID:[Differential diagnosis of infratentorial atrophies by computed tomography (author's transl)]. 708 62

Seventeen patients with Friedreich's ataxia or spastic ataxia were subjected to an urodynamic evaluation. Fifty-three per cent (53%) of the patients presented with urinary symptoms consisting of urgent micturition and urgency incontinence. Cystometric evaluation showed a lack of inhibition of the detrusor in 7 patients (41%). Abnormal electric hyperactivity of the external sphincter was documented in 6 cases (37.5%) by electromyography. Some hypotheses are presented to explain the etiology of these abnormal findings.
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PMID:Urodynamic evaluation of patients with hereditary ataxias. 710 78

The plasma distribution of alpha-keto acids was measured in 26 subjects including 8 patients with Friedreich's ataxia, 8 with the recessive spastic ataxia of Charlevoix-Sageunay and 10 healthy volunteers. The groups were matched with regards to age, sex, weight and the study was conducted under standardized dietary intake. The result indicate significant differences in the alpha-keto acids distribution between the groups.
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PMID:Quantitative metabolic profiling of alpha-keto acids in Friedreich's ataxia. 710 88


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