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)

Currently, echocardiography is the technique of choice in the noninvasive assessment of left ventricular (LV) function. Unlike the assessment of LV systolic function, its role is limited in the quantification of LV diastolic function where only global LV filling can be assessed. Tissue Doppler echocardiography (TDE) is a recently introduced imaging technique which allows for direct assessment of LV myocardial contraction and relaxation. Therefore, parameters derived from TDE showed provide a more accurate assessment of LV systolic and diastolic function. Doppler myocardial velocity gradient (MVG) is a new parameter derived from TDE, which enables the measurement of the spatial distribution of transmyocardial velocities over the cardiac cycle. The most studied application of this technique relates to the earlier and more sensitive diagnosis of different forms of cardiomyopathy. Based on the Doppler MVG measurement, patients with ischaemic cardiomyopathy can be differentiated from those with idiopathic dilated cardiomyopathy. In both diseases MVG is reduced in systole, but as opposed to dilated cardiomyopathy, MVG in patients with ischaemic cardiomyopathy is also markedly reduced in early diastole. MVG derived from TDE also provides new diagnostic insights into genetically determined heart muscle diseases. It has been shown that an early diastolic MVG < or = 7 s-1 is characteristic for patients with hypertrophic cardiomyopathy and differentiates this group of patients from 'athletes' heart, independently of the degree of LV hypertrophy. A recent study has also shown that in Friedreich ataxia related cardiomyopathy there is a close relation between the degree of genotype abnormalities and the degree of reduction in the MVG. Also, the assessment of Doppler MVG enables the differentiation of restrictive cardiomyopathy from constrictive pericarditis. Based on available literature it appears that TDE derived MVG enhances the information available from conventional echocardiography and helps to establish an earlier diagnosis in patients with primary and secondary myocardial diseases.
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PMID:[Doppler myocardial velocity gradient as a new diagnostic index for the assessment of myocardial disease]. 1157 38

A pure selenium deficiency is harmful to the heart and causes a fatal dilated congestive cardiomyopathy in animals (white muscle disease) and in man (Keshan disease). Both of these syndromes are selenium-responsive. A deficiency of the micronutrient has also been reported in patients with Friedreich's ataxia and there are histological similarities between Friedreich's cardiomyopathy and Keshan disease. A low selenium status results in reduced selenium-dependent glutathione peroxidase activity. This essential antioxidant enzyme protects membrances from oxidative deterioration, a function it shares in common with vitamin E. As iron-induced mitochondrial lipid peroxidation is central to the pathology of Friedreich's ataxia, the administration of selenium supplements should normalize the antioxidant activity of myocardial glutathione peroxidase and slow the progression of the life-shortening cardiomyopathy associated with this illness.
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PMID:Rationale for clinical trials of selenium as an antioxidant for the treatment of the cardiomyopathy of Friedreich's ataxia. 1181 88

Cardiomyopathy and neuromuscular abnormalities may simultaneously coexist and present with defects in mitochondrial DNA and bioenergetic function. We sought to evaluate the relationship between clinical and mitochondrial phenotypes in 28 young patients with both cardiomyopathy and neurologic disorders including seizures, dystonia, ophthalmoplegia, Kearns-Sayre syndrome, Leigh disease, and Friedreich's ataxia. All tissues examined displayed marked defects in respiratory complex activities. Five patients had abundant large-scale mitochondrial DNA deletions and one patient displayed a pathogenic point mutation previously reported with mitochondrial cytopathy. In this cohort, patients with hypertrophic cardiomyopathy displayed a higher incidence of complex I defects, fewer DNA deletions and mitochondrial structural abnormalities and were less often associated with developmental delay phenotype compared with patients with dilated cardiomyopathy. Although structural abnormalities are present in a subset of patients, evaluation of respiratory enzyme activity appears to be most informative whether tissues examined were derived from heart or skeletal muscle. Defects in mitochondrial DNA and bioenergetics are frequently present in children with cardiomyopathy presenting with a variety of neurologic abnormalities and are amenable to biochemical and molecular analysis.
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PMID:Cardiomyopathy associated with neurologic disorders and mitochondrial phenotype. 1254 31

Oxygen radicals regulate many physiological processes, such as signaling, proliferation, and apoptosis, and thus play a pivotal role in pathophysiology and disease development. There are at least two thioredoxin reductase/thioredoxin/peroxiredoxin systems participating in the cellular defense against oxygen radicals. At present, relatively little is known about the contribution of individual enzymes to the redox metabolism in different cell types. To begin to address this question, we generated and characterized mice lacking functional mitochondrial thioredoxin reductase (TrxR2). Ubiquitous Cre-mediated inactivation of TrxR2 is associated with embryonic death at embryonic day 13. TrxR2(TrxR2(-/-)minus;/TrxR2(-/-)minus;) embryos are smaller and severely anemic and show increased apoptosis in the liver. The size of hematopoietic colonies cultured ex vivo is dramatically reduced. TrxR2-deficient embryonic fibroblasts are highly sensitive to endogenous oxygen radicals when glutathione synthesis is inhibited. Besides the defect in hematopoiesis, the ventricular heart wall of TrxR2(TrxR2(-/-)minus;/TrxR2(-/-)minus;) embryos is thinned and proliferation of cardiomyocytes is decreased. Cardiac tissue-restricted ablation of TrxR2 results in fatal dilated cardiomyopathy, a condition reminiscent of that in Keshan disease and Friedreich's ataxia. We conclude that TrxR2 plays a pivotal role in both hematopoiesis and heart function.
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PMID:Essential role for mitochondrial thioredoxin reductase in hematopoiesis, heart development, and heart function. 1548 10

Friedreich's ataxia is an autosomal recessive neurodegenerative disease. We report the case of a 34-year-old man with Friedreich's ataxia and dilated cardiomyopathy who underwent successful cardiac transplantation. To our knowledge, this is the first reported case of a heart transplantation for Friedreich's ataxia dilated cardiomyopathy.
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PMID:Cardiac transplantation: a temporary solution for Friedreich's ataxia-induced dilated cardiomyopathy. 1553 31

A patient with Friedreich's ataxia was hospitalized due to dilated cardiomyopathy and heart failure. We received informed consent from the patient and his family for implantation of an implantable ventricular assist device (VAD) as permanent support. At the one-year follow-up examination, the neuromuscular symptoms had progressed no further, and he had no VAD systemic failure and complications. This is the first case report of VAD implantation in a Friedreich's ataxia patient.
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PMID:Permanent use of a ventricle assist device for dilated cardiomyopathy in Friedreich's ataxia. 1644 31

Dilated cardiomyopathy, hypertrophic cardiomyopathy, and cardiac rhythm disturbances are important features of certain neuromuscular disorders in children, adolescents, and young adults. This article summarizes the cardiac features seen in patients with Duchenne muscular dystrophy, Becker muscular dystrophy, myotonic dystrophy, Friedreich's ataxia, and Emery-Dreifuss muscular dystrophy. The optimal management of these cardiac features remains contentious, but increasingly these patients are referred for routine cardiological assessment in the absence of symptoms. This article examines the value of routine screening and drug interventions for cardiac complications in asymptomatic and symptomatic individuals with neuromuscular disorders. We recommend a pragmatic approach, actively looking for cardiac conditions which will benefit from early intervention, but avoiding routine screening for asymptomatic conditions in which there is no evidence of benefit from early intervention.
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PMID:Cardiac monitoring and treatment for children and adolescents with neuromuscular disorders. 1697 70

Excessive body iron or iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis), which are reaching epidemic levels worldwide. Primary hemochromatosis is the most common genetic disorder with an allele frequency greater than 10% in individuals of European ancestry, while hemosiderosis is less common but associated with a much higher morbidity and mortality. Iron overload leads to iron deposition in many tissues especially the liver, brain, heart and endocrine tissues. Elevated cardiac iron leads to diastolic dysfunction, arrhythmias and dilated cardiomyopathy, and is the primary determinant of survival in patients with secondary iron overload as well as a leading cause of morbidity and mortality in primary hemochromatosis patients. In addition, iron-induced cardiac injury plays a role in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, Friedreich ataxia and neurodegenerative diseases. Patients with iron overload also routinely suffer from a range of endocrinopathies, including diabetes mellitus and anterior pituitary dysfunction. Despite clear connections between elevated iron and clinical disease, iron transport remains poorly understood. While low-capacity divalent metal and transferrin-bound transporters are critical under normal physiological conditions, L-type Ca2+ channels (LTCC) are high-capacity pathways of ferrous iron (Fe2+) uptake into cardiomyocytes especially under iron overload conditions. Fe2+ uptake through L-type Ca2+ channels may also be crucial in other excitable cells such as pancreatic beta cells, anterior pituitary cells and neurons. Consequently, LTCC blockers represent a potential new therapy to reduce the toxic effects of excess iron.
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PMID:Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. 1660 32

Friedreich ataxia (FRDA) is the most common cause of childhood onset ataxia. We report on a 4 year old boy who suffered sudden cardiac death and was found to have a dilated cardiomyopathy with left ventricular hypertrophy on post-mortem studies. Molecular genetic testing subsequently confirmed the diagnosis of Friedreich ataxia. To our knowledge, this is the first report of Friedreich ataxia presenting as sudden cardiac death in early childhood.
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PMID:Friedreich ataxia presenting as sudden cardiac death in childhood: clinical, genetic and pathological correlation, with implications for genetic testing and counselling. 2033 62

Friedreich's ataxia (FRDA) has been associated with both cardiac hypertrophy and to a lesser degree dilated cardiomyopathy. We have conducted a cross sectional magnetic resonance imaging (MRI) study of 25 patients with clinically and genetically confirmed FRDA and 24 healthy controls to analyse how disease parameters influence cardiac features in FRDA. MR cine imaging in the long and short axis planes was performed alongside clinical assessments. LV mass was most pronounced in FRDA patients with a larger genetic mutation (GAA1 repeats >600), earlier age of onset (<16years) and a shorter disease duration (<15 years). LV mass decreased with longer disease duration (>15 years), and independent of GAA1 repeat size and age of onset, suggesting cardiac thinning occurred with prolonged disease. Heart function was lower in patients with larger GAA1 repeat number and longer disease duration. Consequently, cardiac hypertrophy was more marked in FRDA patients with a larger GAA1 repeat number and younger age of onset, while prolonged disease duration was associated with lower LV mass and decreased heart function. It is important not only to understand the biochemical basis for these cardiac changes but also allow for these changes when assessing the effect of treatment of FRDA patients.
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PMID:Analysis of the factors influencing the cardiac phenotype in Friedreich's ataxia. 2046 1


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