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)

Friedreich's ataxia is almost always associated with a cardiomyopathy. The cardiomyopathy and its attendant cardiopulmonary sequelae is the usual cause of death in this disease. The author reviews the known pharmacology of the heart, particularly as it applies to hypertrophic cardiomyopathy. The important role played by calcium and the possible role of taurine is stressed. Therapeutic possibilities are mentioned.
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PMID:Cardiac pharmacology and cardiomyopathy in Friedreich's ataxia. 2 6

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

Jejunal mucosa from 7 patients with amyotrophic lateral sclerosis (A.L.S.), 20 newly reported patients with multiple sclerosis (M.S.), and 35 control patients without either disease was studied by immunofluorescence. An immune reaction was present in all A.L.S. specimens and consisted of altered ratios of immunoglobulin-labelled cells in the lamina propria, complement-labelled cells in the same location, and, in some, immunoglobulin and complement deposits in the epithelial basement membrane. Poliovirus antigen was detected in 4 cases, and in 1 of the these cases measles antigen was also present. A fifth specimen showed large amounts of herpesvirus antigen. In 2 cases studied at necropsy, both viral infection and immunological change was confined to the proximal jejunum. Measles antigen was identified in every case of M.S., and in biopsy specimens from 16 of the 20 M.S. patients immunological reactions similar to those seen in A.L.S. were present. With 2 exceptions, the controls did not show these changes in the jejunal mucosa. The exceptions were a patient with Friedreich's ataxia, who had an increase of IgG-labelled cells and some complement-bearing cells in the lamina propria, and a patient diagnosed as having non-tropical sprue, in whom large quantities of herpes antigen were seen.
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PMID:Jejunal immunopathology in amyotrophic lateral sclerosis and multiple sclerosis. Identification of viral antigens by immunofluorescence. 6 22

In contrast to the distal sensory response, the somatosensory evoked response (SSER) is detectable in patients with A-alpha sensory fiber diseases such as Friedreich's ataxia. In four patients with this disease a combined histological and electro-physiological investigation of sensory propagation was performed. The sural nerve was analyzed in terms of the various fiber diameters and the distal sensory and somatosensory evoked cortical responses recorded after sural and median nerve (finger) stimulation. A distinct evoked response could be detected with rather low amplitudes and retarded latency times, while in general no distal sensory response was found. The anatomical physiological consequences are discussed.
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PMID:Somatosensory evoked response in controlled A-alpha sensory fiber disease. 8 60

This joint work has studied the cardiomyopathies occurring in hereditary neuro-muscular disorders (270 cases). The Duchenne type of disorder (74 cases) was responsible for asystole (4 cases), for cardiomegaly, and especially for abnormalities of the ECG (59 cases)--Q waves and large R waves in V1 and V6. The cardiomyopathy was of the hypokinetic type, with histological evidence of degeneration of the myocardial fibres. Dystrophia myotonica of Steinart (23 cases) caused conductive disorders (17 cases) which were either atrioventricular or intra-ventricular or both. Studies of the His pathway confirmed that these abnormalities were more diffuse in 5 cases. The main histological feature was interstitial fibrosis. There was a high risk of sudden death; ECG follow-up should be close. Friedreich's disease (20 cases) in its complete form led to later development of obstructive cardiomyopathy, with a systolic ejection murmur, cardiomegaly, and abnormalities of the ECG--left ventricular hypertrophy in the vertical axis, right ventricular and septal hypertrophy, repolarisation disorders similar to those found in coronary artery disease. Histology showed hypertrophy with degeneration of the myocardial fibres and interstitial fibrosis. This complete form was rare (7 cases out of 20); on the other hand, ECG abnormalites were very common (16 cases out of 20). The authors have tried to study the relationships between primary cardiomyopathies (50 cases) and peripheral neuromuscular disorders. 17 of the 39 peripheral muscle biopsies were abnormal, but a well-defined muscular dystrophy could not be found in them.
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PMID:[The myocardiopathies of hereditary neuro-muscular diseases]. 9 58

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

Taurine and beta-alanine uptake kinetics were studied in cultured skin fibroblasts from 9 patients with Friedreich's Ataxia and 8 controls. No significant difference was observed. The data support the presence of normal beta-amino acid carrier protein in Friedreich's Ataxia cell membrane.
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PMID:Taurine and beta-alanine uptake in cultured human skin fibroblasts from patients with Friedreich's ataxia. 11 97

Most articles on Friedreich's ataxia report that cardiac complications are almost universal in patients with this disease. However, the present study of 30 cases, observed for two to ten years, seems to belie the experience of other writers in the field. Only six (20 per cent) of these patients showed electrocardiographic abnormalities. Only one patient had cardiac enlargement and congestive heart failure. One other patient had paroxysmal tachycardia. Seventy-four family members were also studied and the results were similar. It is suggested that this impressive difference may be a racial one and indeed very few reports on Friedreich's ataxia have come from India. Further study of this group of patients is in progress. The author also includes a review of the literature of neuromyopathic diseases and their relationship to myocardial involvement.
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PMID:Heart in Friedreich's ataxia. 12 3


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