Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CSF findings in hereditary ataxias and allief disorders have hitherto mostly been reported as normal if one excludes Refsum's syndrome. The CSF-protein patterns found on isoelectric focusing and quantitative paper electrophoresis were studied in 12 patients with hereditary ataxias and hereditary spastic paraplegia. Using a recently-developed technique of isoelectric focusing of CSF-proteins in flat beds of polyacrylamide gel, the authors could show abnormal CSF-protein patterns in all but 1 of the present cases. The aberrant CSF-protein patterns found showed differences between the syndromes studied. Two unique patterns with conspicuous fractions in the acid range were observed in patients with Marie-Sanger-Brown's ataxia (mother and daughter) and Holmes' ataxia. A third CSF-protein pattern was found in a sibship with Friedreich's ataxia including a double fraction in the acid region (pI 5.9-6.1) in all 4 subjects and a highly alkaline fraction (HAF) with pI about 9.3, in 3 of them. Similar acid fractions (pI 5.9-6.1) were also detected in 3 of 4 patients with hereditary spastic paraplegia, a brother and sister showing a very similar CSF-protein pattern. Double fractions with pI 5.9-6.1 and/or HAF may also occur in other neurological diseases, mostly, however, associated with other distinctive features of their CSF-protein patterns. A possibility in the future of distinguishing hereditary CNS-diseases by examination of the CSF-protein pattern is suggested.
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PMID:Protein patterns of cerebrospinal fluid in hereditary ataxias and hereditary spastic paraplegia. 4 1

No chromosomal anomaly was found in 15 cases of typical Friedreich's ataxia and three cases of atypical recessive ataxia studied with Q and G banding techniques. No difference between frequency of chromosomes gaps or breakages was noted amongst patients with Friedreich's ataxia and controls.
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PMID:Friedreich's ataxia: observations with Q and G banding of human chromosomes. 6 12

A family is described in which a mother and three of her five children showed myoclonic epilepsy. The mother and one son were also ataxic; one other son had additional features of Friedreich's ataxia, and a daughter had peroneal muscular atrophy as well as myoclonic epilepsy and ataxia. Although some of these disorders have been associated in previously reported families, the occurrence of all three disorders in members of one family seems to be unique. It is concluded that this family shows the manifestations of one, probably dominant, gene. The differences in age of onset and manifestations may be explained by the action of one or more subsidiary genes.
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PMID:Familial myoclonic epilepsy with ataxia and neuropathy with additional features of Friedreich's ataxia and peroneal muscular atrophy. 10 Dec 80

There is now a great deal of evidence to link genetic defects of pyruvate metabolism to brain disease. Experimental evidence is reviewed in Chapter 12, and clinical evidence has been reviewed above. Severe lesions of components of the pyruvate dehydrogenase complex are associated with severe generalized brain disease, and milder defects with inherited ataxias. Nearly half of one series of our ataxic patients had deficient activity of pyruvate dehydrogenase, and 40% of another series have deficient activity of the lipoamide dehydrogenase component. This last group corresponds to 60% of the patients with Friedreich's ataxia and its clinical variants at UCLA. There is an association between defective activity of lipoamide dehydrogenase and disease, and the data suggest there is a structural mutation of the gene for the enzyme. Preliminary studies suggest that obligate heterozygotes as a group have enzyme activities between those for controls and those for patients. Moreover, the obligate heterozygotes from families in which there are kinetic defects of lipoamide dehydrogenase also appear to have kinetic abnormalities of the enzyme. The ataxic patients with reduced lipoamide dehydrogenase activity currently fall into two clinical groups. One is ragged-red ataxia, and the other is a disorder that is a subgroup of the classic Friedreich's ataxia syndrome. Studies need to be undertaken on a larger group of patients, with more diverse inherited ataxias, to test the present clinical associations of the enzyme defect. A dietary treatment derived from a knowledge of the presumed defect has modified the ataxia that is associated with defects of pyruvate decarboxylase, but the diet has not yet been tested with defects of lipoamide dehydrogenase.
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PMID:Evidence for a primary defect of lipoamide dehydrogenase in Friedreich's ataxia. 10 55

A systematic study of plasma lipids and lipoproteins was carried out in 11 cases of Friedreich's ataxia and 6 cases of familial spastic ataxia (Charlevoix-Saguenay disease) using 11 healthy normolipidemic volunteers of comparable age and sex as controls. No differences were noted in the fatty acid profile of the total lipid fraction, in the total cholesterol and phospholipids or in the percentage distribution of the individual phospholipid classes. The triglycerides were significantly higher in Friedreich's ataxia, but remained within the normal range. Although no systematic abnormalities could be detected in the electrophoretic pattern of plasma lipoproteins or in the apolipoprotein profile on polyacrylamide gel electrophoresis, major differences were found in the high density lipoprotein (HDL) fraction. Their total amount was reduced and their composition was abnormal in both neurological diseases. In Friedreich patients, the relative proportion of cholesterol and triglycerides was increased while the relative protein content was greatly reduced. In Charlevoix disease, a similar abnormality was seen except for the excess of triglycerides. The proportion of phospholipids in HDL was the same in the three groups of patients. In addition, the low density lipoprotein (LDL) fraction was slightly reduced in both diseases. This anomaly of the HDL fraction could indicate that the HDL apolipoprotein moiety has a greater affinity for cholesterol and triglycerides in Friedreich's ataxia than its normal counterpart.
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PMID:Plasma lipids and lipoproteins in Friedreich's ataxia and familial spastic ataxia--evidence for an abnormal composition of high density lipoproteins. 20 32

The value of evoked potentials in studying conduction in the somatosensory pathway was assessed in patients with various neurological disorders. In patients with multiple sclerosis (MS) abnormalities of the cervical response (N14) were found particularly in longstanding cases but also in the early stages of the disease, even in patients without sensory symptoms or signs, and were reversible in some patients. The cortical response was also abnormal in some cases but the two were not always affected together. In Friedreich's ataxia both the cervical and cortical responses were usually abnormal. Subclinical abnormalities of the cervical responses were found in some patients with hereditary spastic paraparesis or mixed forms of spinocerebellar ataxia. The cervical responses were also abnormal in patients with peripheral neuropathy and cervical radiculopathy, and in some patients with brain-stem or thalamic lesions. Cervical and cortical responses were normal in the lateral medullary syndrome, whereas the cortical response was markedly abnormal in patients with high brain-stem or cerebral hemisphere vascular lesions. Cortical and subcortical responses were abnormal in some patients with stereotactic thalamic lesions. Enhanced cortical responses were found in patients with lesions at different levels in the CNS. The most marked enhancement was observed in patients with familial myoclonic epilepsy. Lesser degrees were found in some patients with MS, progressive supranuclear palsy, thalamic lesions, brain-stem encephalitis and syringomyelia. Enhanced responses were usually found in patients with minimal or no clinical sensory involvement. It is postulated that this type of abnormality results from an interference to the inhibitory mechanisms which normally operate at various levels in the somatosensory pathway. It is concluded that evoked potential studies are a valuable adjunct to the clinical evaluation of sensation, and that they may provide useful information on the pathophysiology of conduction in the somatosensory pathway.
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PMID:The contribution of evoked potentials in the functional assessment of the somatosensory pathway. 22 50

Abetalipoproteinaemia (Bassen-Kornzweig syndrome), an autosomal recessive inherited disease, up to now has been described in 53 instances in the world literature. Neurological symptoms were reported in 34 of them. Ataxia, loss of proprioceptive sensation, and areflexia characterize this disorder, resembling Friedreich's ataxia. Other signs, which may be inconstantly found, are weakness, diminution of cutaneous sensation, and in the later course an atypical retinitis pigmentosa. Laboratory examinations show acanthocytosis, lowered concentrations of serum cholesterol, triglycerides and phospholipids and as the pathognomonic feature of this disease absence of beta-lipoproteins. Reduced serum concentrations of fat soluble vitamin are secondary effects of this metabolic disorder. In a few cases there are connections to familial hypobeta-lipoproteinaemia, which is autosomal dominantly inherited. Therapeutic trials with a controlled dietary intake of fat may cause an improvement of clinical symptoms, additional doses of fat-soluble vitamin, if given during the early stages of the disease are said to prevent from retinopathy but do not seem to influence the development and course of neuropathy.
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PMID:[Neurological symptoms in a-beta-lipoproteinemia (author's transl)]. 25 73

Twenty four ataxic patients were investigated with electromyography and nerve conduction studies. They were divided in two groups according to the area they came from, the evolution of the disease, and the clinical signs. Group I patients from the Rimouski area displayed all the clinical and electrophysiological signs of Friedreich's ataxia. Group II comprised patients who presented with a new syndrome known as the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Although the clinical evolution was better in the latter, there were more electromyographic signs of denervation and the motor conduction velocities were slower. Both groups showed identical and important abnormalities in sensory nerve conduction. The results of electrophysiological studies in spastic ataxia have not been reported to our knowledge. They underline the place of spastic ataxia as distinct from Friedreich's ataxia, spastic paraplegia, and the known familial neuropathies.
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PMID:Electromyography and nerve conduction studies in Friedreich's ataxia and autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). 48 8

Two female patients aged 30 and 40 years with the Charlevoix-Saguenay ataxia were studied. Both had absent sensory action potentials in upper and lower extremities but, unlike typical cases of Friedreich's ataxia, they displayed a marked slowing of motor conduction velocities. Sural nerve biopsies taken from calf and ankle revealed a severe loss of large myelinated axons contrasting with a normal myelinated fiber density. Evidence for active axonal degeneration was scarce, with no indication of axonal regeneration. Teased myelinated fibers revealed an increased variability of internodal length but no evidence for myelin breakdown. These findings support, as a primary defect, a developmental abnormality of peripheral nerve, namely a lack of maturation of large myelinated axons and possibly a faulty myelination of nerve fibers. We think it is unlikely to represent a progressive axonal atrophic or dystrophic process, as suggested in Friedreich's ataxia.
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PMID:The neuropathy of Charlevoix-Saguenay ataxia: an electrophysiological and pathological study. 48 11

Of 13 patients with Friedreich's ataxia (Type Ia) and 17 with type IIa recessive ataxias, all were found to have levels of "free erythrocyte protoporphyrin" (FEP) above the normal range. The rise in FEP in Friedreich's ataxia correlated well with the age of the individual and thus appears to be related to the course of the disease. Subjects with olivo-ponto-cerebellar atrophy, Charlevoix syndrome, Duchenne muscular dystrophy, and Parkinson's disease were also found to have significantly elevated FEP, although the distribution overlapped with the normal range. The finding of elevated FEP may indicate a relative heme deficiency in ataxia due to inhibition of ferrochelatase leading to a state of ineffective, persistent erythropoiesis. The possibility of a prostaglandin abnormality being related to this defect and to the pathogenesis of ataxia is considered.
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PMID:Erythrocyte protoporphyrin levels in patients with Friedreich's and other ataxias. 48 15


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