Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recent prospective three-year follow-up study of 1931 men in Finland demonstrated a significant 2.2-fold greater risk of acute myocardial infarct in 42- to 60-year-old men who had serum ferritin concentrations above 200 micrograms/dL. However, the mean plasma ferritin concentration in this population was high and the prevalence of hemochromatosis was unknown; these issues mitigate the suggestion that high-normal iron stores leads to heart disease.
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PMID:Are we at risk for heart disease because of normal iron status? 851 89

Atrial fibrillation (AF) is in most patients (approximately 70%) associated with organic heart disease including valvular heart disease, coronary artery disease, hypertension, hypertrophic cardiomyopathy, dilated cardiomyopathy, and congenital heart disease, mostly atrial septal defect in adults. In many chronic conditions, determining whether AF is the result or is unrelated to the underlying heart disease, remains unclear. The list of possible etiologies also include cardiac amyloidosis, hemochromatosis and endomyocardial fibrosis. Other heart diseases, such as mitral valve prolapse (without mitral regurgitation), calcifications of the mitral annulus, atrial myxoma, pheochomocytoma, and idiopathic dilated right atrium may present with AF. Atrial fibrillation may occur in the absence of detectable organic heart disease, the so-called "lone AF", in about 30% of cases. The term "idiopathic AF" implies the absence of any detectable etiology including hyperthyroidism, chronic obstructive lung disease, overt sinus node dysfunction, and overt or concealed preexcitation (Wolff-Parkinson-White syndrome), only to mention a few of other uncommon causes of AF. The autonomous nervous system may contribute to the occurrence of AF in some patients. AF occurs commonly. In patients with valvular heart disease, AF is common, particularly when the mitral valve is involved. The occurrence of AF is unrelated to the severity of mitral stenosis or mitral regurgitation but is more common in patients with enlarged left atrium and congestive heart failure. In patients with coronary artery disease, AF occurs predominantly in older patients, males, and patients with left ventricular dysfunction, Important predictive factors of AF include hypertension, left ventricular hypertrophy and diabetes. The risk of the development of AF, in an individual patient, is often difficult to assess. Increasing age, presence of valvular heart disease, and congestive heart failure increase the risk of atrial fibrillation.
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PMID:Factors predisposing to the development of atrial fibrillation. 935 13

Although rare, amyloidosis and hemochromatosis are the infiltrative diseases in which the heart is more frequently involved. The most common clinical presentation is heart failure with hemodynamic features of restrictive heart disease in cardiac amyloidosis. The diagnosis is often made because of symptoms of other organ involvement, although sometimes cardiac symptoms may be the initial manifestation. The non-specific clinical presentation and the low prevalence of these cardiomyopathies make the diagnosis difficult if the clinician does not suspect it. Once symptoms develop, the evolution is fast. Usually, the unsatisfactory and ineffective treatment of amyloidosis and hemochromatosis contribute to the poor prognosis. The indication of cardiac transplantation in advanced cases is questionable because of the high recurrence of the illness.
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PMID:[Cardiac pathology of extracardiac origin (II). The cardiac repercussion of amyloidosis and hemochromatosis]. 942 3

Hemochromatosis is a recessive disorder of iron metabolism characterized by progressive iron loading of parenchymal organs, which accounts for clinical complications such as cirrhosis, diabetes mellitus, cardiopathy, endocrine dysfunctions and arthropathy. Clinical complications, which usually develop after the third or fourth decade of life, can be fatal but may be prevented by phlebotomy if iron excess is detected at a very early stage. The hemochromatosis gene (HFE), located 4.5 megabases telomeric to the HLA-A locus, encodes an HLA class I like protein and two missense mutations, C282Y and H63D in complete disequilibrium have been identified within this gene. Due to its high frequency in the general population, the involvement of H63D in the pathogenesis of the disease remains controversial, and it might correspond to a minor mutation. Conversely, the C282Y mutation is tightly linked to the disease, as it accounts for 80 to 100% of the hemochromatosis cases in Northern Europe. The lower frequency observed, in the patients, in Italy and South of France led to imagine either the implication of other mutations or of other genes. The C282Y mutation is absent in Asia and Africa and is present in the general population with a decreasing gradient of frequency from Northern to Southern Europe. The prevalence of the disease was usually estimated to be 3% but the observed frequency of the C282Y homozygotes is 5% in our breton population raising the question of the penetrance of the disease, and consequently the use of the genotypic test for its systematic screening. As HFE encodes a membrane protein similar to HLA class I protein, its contribution to iron overload is not obvious. The normal protein is predicted to to be expressed at the cell surface in association with beta 2-microglobulin, a localization for which C282Y is critical as it disrupts this association. This protein has also been shown to form a stable complex with the transferrin receptor leading to a decreased affinity for transferrin. A better knowledge of its function will help to decipher iron and different metal-ions metabolism. Although the exact role of the HFE protein is unknown, the genotypic test allows the clinicians to ascertain their diagnosis and genetic counselling.
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PMID:[Molecular genetics of hemochromatosis]. 1052 Apr 11

Genetic hemochromatosis is an autosomal recessive disease, characterized by an increased iron absorption, leading to progressive iron overload. The fully expressed phenotype comprises fatigue, skin pigmentation, liver disease with hepatomegaly, cirrhosis and hepatocellular carcinoma, and diabetes. Arthralgias are frequent, cardiopathy or impotence may occur. This presentation is now unfrequent with earlier diagnosis, and patients are often asymptomatic--with only biochemical expression--or pauci-symptomatic (mild fatigue, arthralgias or increased transaminases). Transferrin saturation is always increased. Serum ferritin is proportional to iron burden. Diagnosis is now easy, since most patients are homozygote for the C282Y mutation of the HFE gene. Liver biopsy can be useful to quantify iron overload and assess liver fibrosis. The disease can be lethal due to liver disease, carcinoma or heart disease, but life expectancy goes to normal if patients are treated before the occurrence of cirrhosis. Treatment relies on regular venesections. Familial screening is essential.
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PMID:[Diagnosis and treatment of genetic hemochromatosis]. 1086 97

Hereditary hemochromatosis (HH) is common among Caucasians; reported disease frequencies vary from 0.3 to 0.8%. Identification of a candidate HFE gene in 1996 was soon followed by the description of two ancestral mutations, i.e., c.845G-->A (C282Y) and c.187C-->G (H63D). To these was recently added the mutation S65C, which may represent a simple polymorphism. The incidence of HH in Greece is unknown but clinical cases are rare. Also unknown is the carrier frequency of the two mutant alleles. A first estimate of the latter is given in the present report. It is based on data from the genetic analysis of 10 unrelated patients of Greek origin who were referred to our center for genotyping and 158 unselected male blood donors. The allele frequencies for the C282Y and H63D mutations were 0.003 and 0.145, respectively. The C282Y allele was detected in 50% of HH patients. This is considerably lower than the frequencies reported for HH patients in the U.S.A. (82%) and France (91 %) and closer to that reported in Italy (64%). Five patients did not carry any known HFE mutation; three may represent cases of juvenile hemochromatosis, given their early onset with iron overload, hypogonadism, and heart disease. We suggest that genetic heterogeneity is more prominent in Southern Europe. It is also possible that the penetrance of the responsible genes is different across the Mediterranean.
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PMID:Hereditary hemochromatosis: HFE mutation analysis in Greeks reveals genetic heterogeneity. 1100 26

Genetic testing for the C282Y mutation of the HFE gene has been a major advance in the diagnosis of hereditary hemochromatosis. In most studies, more than 90% of typical hemochromatosis patients are homozygous for the C282Y mutation. Large-scale population screening studies in predominantly Caucasian populations have demonstrated a high prevalence of C282Y homozygotes of approximately 1 in 300. Despite this high prevalence by genetic testing, the clinical diagnosis of hemochromatosis and mortality from the disease are much less common. One possibility is the presence of many undiagnosed cases with nonspecific symptoms, and deaths occurring that are attributed to liver disease, diabetes, and heart disease without the recognition of iron overload secondary to hemochromatosis. Another possibility is a high prevalence of nonexpressing homozygotes. In this review, the available data on nonexpressing C282Y homozygotes is collected including information on pathogenesis, environmental interactions, and implications for population screening using genetic testing.
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PMID:Nonexpressing homozygotes for C282Y hemochromatosis: minority or majority of cases? 1100

Secondary and infiltrative cardiomyopathies are the least common forms of cardiomyopathy and often are the most difficult to treat. In all cases, efforts should be made to establish a specific diagnosis because the removal or avoidance of the causative agent (eg, alcohol, cocaine, persistent tachycardia) holds the best promise for reversal of ventricular dysfunction. Patients who present with a dilated cardiomyopathy (DCM) should be treated with standard heart failure therapy. However, the "standard" is changing and clinicians need to take heed of results of recent trials establishing the role of beta-blockers, aldosterone, and angiotensin receptor antagonists in addition to the regimen of digoxin, diuretics and angiotensin-converting enzyme (ACE) inhibitors. In contrast, patients who present with a more infiltrative clinical picture often manifest more diastolic dysfunction and need strict volume control to maintain euvolemia. For patients with biopsy-proven myocarditis, immunosuppressive therapy generally should be considered in an effort to maintain and potentially improve ventricular function. Patients with sarcoid heart disease have shown the greatest response to high-dose corticosteroids. Patients with hemochromatosis related cardiomyopathy should be treated with iron chelation therapy and phlebotomy. The role of cardiac transplantation is limited, as most of the secondary and infiltrative causes of cardiomyopathy are associated with an adverse posttransplant outcome. Other surgical options, such as left ventricular assist devices, may offer hope to patients who would otherwise be ineligible for cardiac transplantation. On the horizon, biventricular pacing and treatments targeted at cytokines and hormonal receptors hold the promise of improving symptoms and prolonging survival by counteracting the deleterious effects of these secondary mediators.
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PMID:Secondary and Infiltrative Cardiomyopathies. 1109 42

The content of body iron is regulated primarily by absorption since humans have no physiological mechanism by which excess iron is excreted. This regulation, however, is not absolute. Many factors such as the content of diets, iron doses, life styles, etc. influence iron absorption. In the past, nutrition programs for iron fortification and the ingestion of iron preparations have been widely practiced because of the seriousness of worldwide iron deficiency. Also, we now know that a significant number of asymptomatic people carry the hemochromatosis gene, HFE, indicating that these people have the potential to accumulate excess body iron in their lifetime. Excess body iron can be highly toxic. This toxicity involves many organs leading to a variety of serious diseases such as liver disease, heart disease, diabetes mellitus, hormonal abnormalities, dysfunctional immune system, etc. The tissue damage associated with iron overload is believed to result primarily from free radical reactions mediated by iron. Iron is an effective catalyst in free radical reactions. The diseases associated with iron overload can be managed effectively or prevented. Therefore, early diagnosis of iron overload and appropriate therapy are critical. By providing the necessary laboratory data, clinical chemistry laboratories can play the pivotal role in the management of these health problems.
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PMID:Chronic iron overload and toxicity: clinical chemistry perspective. 1151 32

We report on a female preterm infant with hepatic failure and neonatal tissue siderosis of hemochromatotic type diagnosed by using both histochemistry and atomic absorption spectroscopy. The infant presented with meconium ileus, signs of rapidly progressive hepatic failure, and hyperferritinemia (7132 ng/ml). Despite surgery and intensive care the infant died 32 days after birth. Postmortem examination showed a wrinkled liver with extensive collapse of the hepatic architecture and regenerating nodules as well as hepatic and extrahepatic iron accumulation of hemochromatotic type, sparing the reticuloendothelial system. Atomic absorption spectroscopy confirmed an increase in the iron content of various organs: liver, heart, pancreas, oral salivary gland, kidney, and adrenal gland. The increase in the iron content of various organs was determined by comparing the analysis of the propositus with those of 5 gestationally age-related preterm infants who had died in the intensive care unit: 2 died of meconium aspiration syndrome, the other 3 of hyaline membrane disease, bronchopulmonary dysplasia, and immaturity, respectively. We also compared the analysis of 15 fetuses having a a condition predisposing to iron accumulation (trisomy 21, trisomy 18, cytomegalovirus, amnion infection syndrome, Rhesus- and ABO-incompatibility, congenital hemolysis, anti-phospholipid syndrome, congenital heart disease). Delta F508, the most frequent mutation seen in cystic fibrosis patients, was excluded by gene sequencing. Different noxae causing iron accumulation in the neonatal period have led to the statement that neonatal hemochromatosis may collect different etiologies, such as metabolic disorders, infections, chromosomal aberrations, and immunological disorders. In this study, we report the singular evidence of neonatal iron accumulation of hemochromatotic type in an infant presenting with meconium ileus and propose a classification of the neonatal disorders associated with iron accumulation.
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PMID:Hepatic failure with neonatal tissue siderosis of hemochromatotic type in an infant presenting with meconium ileus. Case report and differential diagnosis of the perinatal iron storage disorders. 1170 Aug 92


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