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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical characteristics of ten patients with Friedreich's disease are presented. Two cases were members of the same family, another patient had a brother with the disease, and in two cases there was consanguinity. The dominant inheritance pattern was absent in all cases. Initial symptoms and clinical signs were present under 5 years of age in six cases, and in three of them under 2 years of age. As reported in other series, in our cases the disorder first appeared in the legs. Other early manifestations included skeletal deformities and dysarthria, as well as diplopia, paresthesias and dizziness. Friedreich's ataxia results from pyramidal tract degeneration and changes in the cerebellum. Babinski sign was present in nine patients. Other findings were: muscular weakness, distal amyotrophy and distal dystonia. Two patients suffered epileptic attacks with typical EEG pattern. Kyphoscoliosis and pes cavum were constant skeletal deformities. ECG revealed signs of myocardial ischemis in nine patients, although none of them had symptomatology of heart disease. Glucose tolerance test carried out in three cases showed diabetic curves. Results of nerve speed conduction were as follows: normal in one case; decreased sensitive speed conduction in four cases, and decrease of both sensitive and motor speed conduction in other four cases. EMG showed signs of chronic denervation in three cases. These results coincide with those published by other authors.
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PMID:[Friedreich's disease. Clinical study of ten cases (author's transl)]. 737 33

Left ventricular function was assessed in seven patients with Friedreich's ataxia using computer-assisted analysis of the left ventricular echocardiograms and compared with those of 45 normal children matched for age and sex. The left ventricle in Friedreich's ataxia was symmetrically hypertrophied, cavity dimension was normal or small, and septal motion and peak velocity of circumferential shortening were normal in all patients. In diastole the duration of rapid filling was normal, peak rate of increase in left ventricular dimension was reduced in two patients, mitral valve opening was delayed with respect to minimum cavity dimension in seven, and there were significantly greater than normal increases in left ventricular dimension during the isovolumic period to mitral valve opening in seven, indicating abnormal and incoordinate relaxation. Peak rates of posterior wall systolic thickening and diastolic thinning were reduced in four and six patients, respectively, whereas peak rates of septal systolic thickening and diastolic thinning were reduced in one and four, respectively, suggesting a disproportionately greater impairment of the posterior wall than of septal function. The absence of asymmetric septal hypertrophy and mid-systolic closure of the aortic valve, the presence of normal septal motion, and the greater reduction in posterior wall than in septal dynamics are inconsistent with previous ideas that the heart disease of Friedreich's ataxia is identical to hypertrophic cardiomyopathy. Computer-assisted analysis of echocardiograms permits recognition of heart disease in Friedreich's ataxia before the onset of cardiac symptoms or development of clinical signs of heart disease.
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PMID:Left ventricular function in Friedreich's ataxia. An echocardiographic study. 742 88

The association between Friedreich's ataxia and heart disease is well known. Microvascular disease and spasm of coronary arteries have been reported. We report now a patient with the association between this disease and acute myocardial infarction, which raises the hypothesis that it may be related with the already known cardiac abnormalities in this disease.
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PMID:[Acute myocardial infarct and Friedreich's disease]. 788 66

Friedreich ataxia is an autosomal recessive neurodegenerative disorder. The genetic homogeneity to the FRDA locus on chromosome 9q13-21.1 has been observed in families from different ancestries. We report a Spanish family with two affected and three unaffected children. The segregated classical Friedreich ataxia did not show the expected linkage. The analysis focusses on flanking markers FR1, FR2, FR7 and FR5, excluding linkage 1 cM around the FRDA locus. The unique clinical hallmark in this family was the absence of cardiomyopathy after a long-term follow-up in the two affected children. In both patients serum vitamin E levels were normal. The present observations support the existence of a second locus in Friedreich ataxia, and we suggest that this form could be clinically characterized by the absence of muscular heart disease.
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PMID:A family segregating a Friedreich ataxia phenotype that is not linked to the FRDA locus. 864 4

Twelve patients with Friedreich's ataxia (FA) were evaluated clinically and echocardiographically for evidence of heart disease. Electrocardiographic and echocardiographic abnormal findings were discovered in eight (67%) and seven (58%) children, respectively. A high incidence of cardiac involvement is well known in FA cases. Although the patient number in the present study is small, the findings are consistent with those in the literature. The most common pathology was asymmetric septal hypertrophy (ASH), followed by concentric left ventricular hypertrophy (CLVH) and dilated cardiomyopathy (DC).
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PMID:Heart disease in Friedreich's ataxia: a clinical and echocardiographic study. 884 May 35

Friedreich's ataxia (FA) represents a degenerative, genetically determined disease of the nervous system in combination with myocardial affection and in some cases endocrinological disturbances. Manifestation of myocardial involvement usually follows symptoms of nervous system degeneration later in the course, but seems not to be secondary. These cardiac disturbances are the main cause of death in FA-patients. Therapeutic management of heart disease is possible and interdisciplinary neurologic-cardiologic cooperation should start early in the course of FA.
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PMID:[Friedreich disease. A neurocardiologic syndrome with uncertain nosologic classification of heart involvement]. 938 Feb 17

Paediatric cardiology is a dynamic field of progress for results. Those which have marked the year 1999 include the introduction of new techniques of cardiovascular imaging and interventional cardiology, and the new consequences of collaboration with workers in foetal cardiology and medical and molecular genetics. The advances in imaging are the result of those of microprocessors which enable three-dimensional reconstruction of ultrasonic, radiological or magnetic resonance images. This provides intracardiac or intravascular views which are very similar to those seen by the surgeon. This is a major tool for improving the diagnosis and treatment of congenital heart disease. Similarly, the introduction of programmes of tissue recognition enables fine ultrasonic analysis of the vascular wall and of endothelial function leading to the opening of a new chapter of preventive vascular medicine from the earliest age. Paediatric interventional cardiology has also progressed rapidly and the past year has been that of a consensus on the closure of a great number of atrial septal defects by new prostheses implanted and anchored in a simpler and safer manner. Prenatal diagnosis has become a crucial factor in the treatment and prognosis of congenital heart disease which is life-threatening in the first hours of life, explaining the benefit when this is applied to transposition of the great vessels or to coarctation of the aorta. Finally, advances in genetics have led to the identification of several genes of heart malformations and the correlations between interstitial microdeletions and syndromes often associated with heart disease: chromosome 22q11 and the Di George syndrome, chromosome 7q and the Williams syndrome. They have even allowed linking of myocardial and cerebellar abnormalities of a degenerative neuropathy (Friedreich's disease) to an abnormality of the mitochondrial respiratory chain, thus giving the opportunity of a real treatment.
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PMID:[The best of pediatric cardiology in 1999]. 1072 49

There are many neuromuscular diseases associated with cardiomyopathy. Cardiac involvement with progressive muscular dystrophy (Duchenne and Becker type) and some type of limb-girdle muscular dystrophy were characterized by impaired left ventricular systolic function, such as dilated cardiomyopathy like status. In Friedreich ataxia various types of left ventricular hypertrophy were reported. While in myotonic dystrophy and Emery-Dreifuss muscular dystrophy, conduction disturbance and tachyarrhythmia are common types of cardiac manifestation. The severity of cardiac involvement in these diseases is not necessarily concordant with that of skeletal muscle. Recently the genes of these diseases were identified by linkage analysis. We review cardiac abnormalities of these diseases, especially relationship between severity of cardiac disorder and gene abnormalities.
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PMID:[Secondary cardiomyopathy accompanied by neuromuscular disorders]. 1088 12

Friedreich's ataxia is an autosomal recessive neuro-degenerative disorder involving both central and peripheral nervous system. Patients also show a systemic clinical picture presenting heart disease and diabetes mellitus or glucose intolerance. The disease is caused by mutations in the FRDA gene mapped on chromosome 9q13. The product of the gene is frataxin, an 18 kDa soluble mitochondrial protein with 210 amino acids. Crystal structure suggests a new, not previously reported, protein fold. The most frequent mutation is the expansion of a GAA trinucleotide repeat located within the first intron of the gene, and represents 98% of the mutations. Point mutations are described in compound heterozygous subjects with one expanded allele. A two-step model of GAA normal alleles towards premutation alleles, which might generate further full expanded mutations in the population with Indo-European ancestry, has been postulated. Clinical phenotype is variable and an inverse correlation with the GAA expansion size has been observed. Analysis of the GAA triplet is a strong molecular tool for clinical diagnosis, genetic counselling and prenatal diagnosis. Friedreich's ataxia patho-genesis is not solved yet. Substantial data from organism models, such the S. cerevisae yeast and more recently conditioned knock-outs in mouse, and studies in heart biopsies and fibroblast cultures from patients suggest an important role of mitochondrial iron in the development of the disease. Iron is accumulated in the mitochondrial matrix of both the yeast frataxin deficient mutant and the patient fibroblasts. It has been postulated that iron-induced oxygen radical affects the oxidative phosphorylation in frataxin deficiency states favouring the disease pathology. A second hypothesis postulates a direct role of frataxin in the mitochondrial energy activation and oxidative phosphorylation. Iron chelator drugs and antioxidant drugs have been postulated for Friedreich's treatment. No results from clinical trials are available yet, but idebenone, a short-chain quinone, seems to reduce the size of hypertrophic cardiomyopathy and levels of oxidative stress molecules in patients.
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PMID:Friedreich's ataxia and frataxin: molecular genetics, evolution and pathogenesis (Review). 1135 Dec 69

Frataxin is present in mitochondria of all eukaryotes as well as in the cytoplasm of bacteria. In humans, reduced expression of frataxin is associated with Friedreich's ataxia, a recessive inherited neurodegenerative and cardiac disorder leading to reduced life expectancy. Experimental evidences suggest that frataxin acts as an iron-chaperone protein, donating iron to the proteins involved in [Fe-S] cluster assembly and heme synthesis. It also possibly contributes to the process of iron detoxification and storage. The frataxin homolog from Arabidopsis thaliana (AtFH) is a single nuclear-encoded gene targeted to mitochondria and sharing 65% similarity with animal frataxin. In the present work, we show that the knocking out of AtFH gene causes arrest of Arabidopsis embryo development at the globular stage. Consistently with that, we also show by in situ hybridization that AtFH is expressed, in wt Arabidopsis plants, in ovule primordia as well as in embryos at various stages of development, suggesting a key role of plant frataxin during embryogenesis.
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PMID:Knockout of frataxin gene causes embryo lethality in Arabidopsis. 1725 6


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