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 (F.A.) is a degenerative disease which commonly leads to premature death of cardiorespiratory origin. To explain the early death of these patients, previous investigations have established the existence of 1) a cardiomyopathy in nearly 100% of cases, 2) a restrictive pulmonary syndrome of scoliotic origin and 3) a mild hypoxemia associated with slight respiratory alkalosis and a normal oxyhemoglobin dissociation curve. To further assess the cause of early death in patients with such neuromyopathy, we evaluated, in eleven F.A. patients, the sensitivity of the respiratory centers to hypercapnia, hypoxia, and hyperoxia. Ventilatory (VE, VT, F, VT/Ti) and occlusion pressure (P0.1) responses were taken as indices of the respiratory centers output during progressive hypercapnia (Read's method) and isocarbic hypoxia (Weil's method). We studied 11 Friedreich's Ataxia patients and 11 age, sex, and armspan matched controls. The responses of patients to hypercapnia were significantly greater than controls but their responses to hypoxia were similar to controls. Our study establishes that the respiratory centers are functioning adequately in early Friedreich's Ataxia and do not contribute to cardio-respiratory insufficiency in such neuromyopathy.
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PMID:Regulation of respiration in Friedreich's ataxia. 48 4

The prospective investigation of 50 cases of possible Friedreich's ataxia has permitted the clinical and biochemical celineation of the typical disease and an hypothesis on its pathogenesis. A tentative definition of the disorder could read: "Friedreich's ataxia is a progressive degenerative disease always inherited in an autosomal recessive fashion and characterized by a cardiomyopathy and a ganglioneuropathy with dying back phenomenon. It is probably secondary to a defect in the membrane transport of taurine and beta-alanine and/or a defect in the regulation of pyruvate oxidation." The existence of two pathogenetically distinct distinct entities with the same phenotype is a strong possibility.
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PMID:Friedreich's ataxia 1976-an overview. 100 Apr 26

Heart involvement is frequent in Friedreich's ataxia (FA), the most prevalent of the spino-cerebellar degenerative diseases, which is inherited with an autosomal recessive pattern. However, the pathophysiological link between cardiac and neurological disorders is not yet clearly established. We compared a group of 10 patients with FA to a control group (C) of 16 normal subjects, using Doppler-echocardiography. To see whether cardiac involvement was specific to FA, the data of patients with FA were also compared to those of patients with autosomal dominant olivo-ponto-cerebellar atrophia (OPCA), another spino-cerebellar degenerative disease. There was an increase in left ventricular mass index in FA (154 +/- 9 g.m-2 vs 99 +/- 7 g. m-2 in C, P < 0.001), systolic function was normal, the ejection fraction (EF) slope and E/A ratio were decreased (85 +/- 9 mm.s-1 vs 130 +/- 7 mm.s-1 in C, P < 0.001 and 1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.01, respectively), while the isovolumic relaxation period was increased (96 +/- 3 ms vs 92 +/- 2 ms in C, P < 0.01). Deceleration time and time-velocity integrals of A wave to total mitral flow were not modified. In OPCA only the E/A ratio was decreased (1.5 +/- 0.1 vs 1.7 +/- 0.1 in C, P < 0.05). These data show the presence of cardiomyopathy in FA with left ventricular hypertrophy and suggest the presence of diastolic function abnormalities. The cardiomyopathy seems specifically associated with FA and not to spino-cerebellar degenerative disease in general.
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PMID:Cardiomyopathy in Friedreich's ataxia: a Doppler-echocardiographic study. 139 14

Friedreich's ataxia (FA) is a progressive degenerative disease involving both central and peripheral nervous system. It is an autosomal recessive hereditary disorder, which begins around puberty and has an unknown genetic basis and biochemical defect. The recent mapping of FA locus in human chromosome 9 by means of the analysis of the molecular genetic linkage has permitted to evaluate FA genetics with polymorphic genetic markers (RFLPs) that are secreted linked with the FA gene. The normal and mutant allele secretion of FA was evaluated in ten Spanish families with one or two members with FA by means of several cloned probes (MCT112, DR47, D9S1 and HHH220), localized in chromosome 9 and strongly linked to FA gene, with the aim of achieving a predictive diagnosis of relatives in the pediatric age and to detect healthy carriers. In 9 out of 10 families some totally or partially informative RFLP were found. In 5 of 6 relatives in pediatric age the future development of the disease could be ruled out. By contrast, the carrier status could only be identified in three relatives. In a family with two affected children a genetic recombinant for D9S1 was found. Remarkably, one of them had a better clinical evolution and preserved tendon reflexes in lower limbs.
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PMID:[Genetic analysis of Friedreich's ataxia using polymorphic DNA markers]. 197 90

Friedreich ataxia (FA) is an autosomal recessive degenerative disease of the nervous system of unknown biochemical cause. The FA gene has been shown to be in close linkage with the two chromosome 9 markers D9S5 and D9S15, and linkage disequilibrium between FA and D9S15 has been detected in French families by Hanauer et al. We used new highly informative markers at the above loci to analyze Italian FA families for linkage and linkage disequilibrium. The new markers were a three-allele BstXI RFLP at D9S5 (PIC = .55) and a six-allele microsatellite, typed by polymerase chain reaction, at D9S15 (PIC = .75). We obtained maximum lod scores of 8.25 between FA and D9S5, 10.55 between FA and D9S15, and 9.52 between D9S5 and D9S15, all at zero recombination. Our results, combined with those reported by other authors, reduce maxlod-1 (maximum lod score minus 1) confidence limits to less than 1.1 cM between FA and D9S5, 1.2 cM between FA and D9S15, and 1.4 cM between D9S5 and D9S15. Linkage disequilibrium with FA was found only for D9S15 when all families were evaluated but was also found for a D9S5/D9S15 haplotype in a subgroup of southern Italian families. We conclude that FA, D9S5, and D9S15 are tightly clustered and that studies of geographically restricted groups may reveal a limited number of mutations responsible for the disease in the Italian population. We present preliminary evidence from pulsed-field gel electrophoresis that D9S5 and D9S15 may be less than 450 kb apart. Linkage disequilibrium between FA and D9S15 suggests that the disease gene may be at an even shorter distance from this marker locus, which therefore represents a very good starting point for cloning attempts.
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PMID:Friedreich ataxia in Italian families: genetic homogeneity and linkage disequilibrium with the marker loci D9S5 and D9S15. 237 48

Friedreich's ataxia (FA) is an hereditary degenerative disease involving the spino-cerebellar via which in 10-15% of the cases is associated with symptomatic cardiac disease. Abnormal ECG or ECHO finding are present even in absence of cardiac symptoms in 100% of the patients. A 7 y.o. girl with the clinical picture of FA with cardiac involvement is presented. The features of the cardiomyopathy present in FA studied with ECHO, myocardial perfusion with Thallium 201 and with histologic examination and its relationship with the hypertrophic cardiomyopathy are discussed. Different theories aiming to discover a unique biochemical factor responsible of both the neurological and cardiac disorders are presented.
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PMID:[Cardiomyopathy in Friedreich's ataxia]. 378 77

In the light of the recent finding of deposits of calcium salts and iron in myocardial cells in one case of Friedreich's ataxia, we have made a detailed morphological study of 3 new cases of this cardiomyopathy. Calcium deposits were not found in the muscle fibers but lipofuscin granules and deposits of iron were observed in our 3 cases. In addition to the usual findings of interstitial fibrosis, hypertrophy and degeneration of myocardial fibers, foci of segmental active muscle necrosis were constantly present. There is a possibility that Friedreich's ataxia could be a neurocardiac degenerative disease with a membrane defect which could be related to defective metabolism of vitamin E or other micronutrients.
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PMID:The cardiomyopathy of Friedreich's ataxia morphological observations in 3 cases. 645 94

Friedreich's ataxia (FA) is a progressive, spinocerebellar degenerative disease. Onset is generally in the second decade of life, occurring as a neurologic degenerative process. Most, if not all, patients have an associated cardiomyopathy, which is frequently the cause of death. We studied two siblings who had FA with acute cardiomyopathy at 3 and 5 years of age, respectively, and in whom the classic nervous system signs developed, only later. The diagnosis of FA should be considered in patients of any age who have unexplained cardiomyopathy.
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PMID:Friedreich's ataxia with acute cardiomyopathy. 736 3

Cardiac function is affected in up to 90% of patients with Friedreich's ataxia, the most common spinocerebellar degenerative disease. Friedreich's ataxia typically causes motor abnormalities of the extremities, mainly impairing walking and the coordination of the legs and arms. The myocardium is affected at a later stage of the disease. The extent and timing of myocardial involvement determines the clinical course. Some patients have no cardiac symptoms and cardiac involvement can be established only by electrocardiographic or echocardiographic examination. In addition some pathological studies have found evidence of coronary abnormalities, mainly in the small vessels. There are no reports that such lesions cause angina. In a 16 year old patient chest pain on exercise had been the presenting symptom of Friedreich's ataxia at the age of 9. Considerable alterations in ventricular repolarisation on the electrocardiogram suggested a congenital coronary abnormality or hypertrophic myocardiopathy. The results of a Doppler echocardiography, Holter monitoring, and a haemodynamic study with coronary arteriography were all normal. An exercise test when the boy was 13 indicated significant changes in ventricular repolarisation. Myocardial scintigraphy (99mTc-MIBI) at that time, however, was normal. He improved slightly when he was treated with verapamil. When he was 15 neurological symptoms developed and Friedreich's ataxia was diagnosed. Typical angina during exercise seems to have been the first symptom of Friedreich's ataxia.
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PMID:Chest pain during exercise as first manifestation of Friedreich's ataxia. 748 66

Friedreich's ataxia (FRDA) is an autosomal recessive, degenerative disease that involves the central and peripheral nervous systems and the heart. A gene, X25, was identified in the critical region for the FRDA locus on chromosome 9q13. This gene encodes a 210-amino acid protein, frataxin, that has homologs in distant species such as Caenorhabditis elegans and yeast. A few FRDA patients were found to have point mutations in X25, but the majority were homozygous for an unstable GAA trinucleotide expansion in the first X25 intron.
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PMID:Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. 859 8


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