Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemochromatosis is a disorder of iron metabolism that causes progressive damage to the liver, pancreas, heart and other organs. It is the most common autosomal recessive disorder among whites, and it occurs five times more frequently in males than in females. Manifestations include diabetes mellitus, hepatic dysfunction, congestive heart failure and other end-organ insufficiency. The presentation of hemochromatosis is often nonspecific, requiring the clinician to maintain a high index of suspicion. The diagnosis is suggested by abnormal iron studies, most notably an elevated serum ferritin level and/or transferrin saturation. Liver biopsy can confirm the diagnosis and document the presence of cirrhosis. The diagnosis is also supported by characteristic findings on a magnetic resonance imaging scan, and a diagnostic response to repeated phlebotomy (a hematocrit level that rapidly returns to normal). Phlebotomy treatments reduce the total body iron load, prevent continuing deposition of iron in the tissues, and prevent premature morbidity and mortality. Screening is recommended in affected families, and screening programs for wider populations are being evaluated.
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PMID:Hemochromatosis: diagnosis and management. 905 15

Hemochromatosis is an autosomal-recessive disease which causes iron-overload of various organs including liver, pancreas and heart. This report analyzes the course of hemochromatosis in two patients (a 28-year-old man and a 57-year-old woman) in whom hemochromatosis was detected because of severe cardiomyopathy. Initial symptoms were edema, anasarca and dyspnea. Further examinations showed pleural effusion, decreased left-ventricular-function, skin pigmentation, diabetes mellitus and liver cirrhosis. Although phlebotomy treatment and iron-chelation therapy with deferoxamine initially resulted in some improvement, both patients died from cardiomyopathy three months after diagnosis. The reports of these two cases underline that hemochromatosis-associated cardiomyopathy is often irreversible if severe congestive heart failure is present. In cardiac decompensation heart transplantation has to be considered as early as possible.
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PMID:-Cardiomyopathy as the cause of death in genetic hemochromatosis-. 865 Sep 71

The relationship between alcoholism and hereditary hemochromatosis remains controversial. Previous studies have included patients with alcoholic siderosis rather than hereditary hemochromatosis. In this retrospective study, the clinical features, iron status, alcohol history, liver histology, and long-term survival were reviewed in 105 homozygotes for hemochromatosis using rigid diagnostic criteria including an HLA identical sibling with iron overload. Heavy alcohol consumption (>80 g ethanol/day) was found in 15 percent of hemochromatosis patients. Histological features of alcoholic liver disease (Mallory's hyaline bodies, pericentral fibrosis, polymorphonuclear infiltrate, and fatty infiltration) were uncommon in hemochromatosis. Hemochromatosis patients with heavy alcohol consumption had a higher prevalence of cirrhosis than hemochromatosis patients without heavy alcohol consumption. Hepatic iron concentration and hepatic iron index did not significantly differ between these two hemochromatosis groups. Long-term survival was significantly reduced in patients with heavy alcohol consumption (mean follow-up, 9.22 years). This suggests that chronic alcohol consumption has an additive hepatotoxic effect despite the paucity of histological features of alcoholic liver disease.
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PMID:Alcoholism in hereditary hemochromatosis revisited: prevalence and clinical consequences among homozygous siblings. 866 24

We described a clinicopathological study of primary hepatoma associated with alcoholic liver diseases without viral liver diseases. In 150 patients with primary hepatoma, 6 patients (4%) have hepatoma associated with pure alcoholic liver disease, although 143 hepatoma were associated with chronic viral liver diseases and one was with primary biliary cirrhosis. All patients were male. The diagnosis of hepatoma was obtained at the age of 54 to 67 years old, and the duration of ethanol intake was 33 to 40 years. Three cases had a history of temperance. As an underlying liver disease, liver fibrosis was found in 3 cases and liver cirrhosis was in 3 cases. Chronic infections of hepatitis B and C viruses were ruled out by assaying serum virus markers. Autoimmune hepatitis and primary biliary cirrhosis were neglected by serum autoantibody. Hemochromatosis and Wilson's disease were also excluded. Hepatocellular carcinoma was diagnosed histologically in all the cases. Serum alpha-fetoprotein and PIVKA-II were positive in patients with advanced hepatocellular carcinoma. In cases with small hepatoma, the tumor was resected surgically in two cases and percutaneous ethanol injection against hepatoma was performed in one case. In these cases with small hepatoma, the patients were alive without tumor recurrence during observation period. In advanced hepatoma, transcatheter arterial infusion of anticancer agent was performed in two cases and no therapy was performed due to poor general condition in one case. One case was alive with recurrent hepatoma for 27 months, during which a therapy was repeated five times. Other 2 cases were died. The clinicopathological features of hepatoma associated with alcoholic liver disease were essentially same as those associated with chronic viral infection, although the incidence of hepatoma in alcoholic liver disease was lower than in viral liver disease. The mechanism of hepatocarcinogenesis in alcoholic liver disease was unclear and, therefore, further study of molecular biology and biochemistry was necessary.
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PMID:[A clinicopathological study of primary liver cancer associated with alcoholic liver injury]. 869 40

Hemochromatosis is the most common genetic disorder known in man and results in progressive tissue deposition of iron leading to cirrhosis of the liver, hepatic carcinoma, congestive heart failure, endocrinopathies, and premature death. SFT (stimulator of Fe transport) is a newly discovered transport protein that facilitates uptake of iron. Recent studies have demonstrated that although SFT expression is reciprocally regulated in response to cellular iron levels, it is aberrantly upregulated in the liver of hemochromatosis patients, indicating that enhanced SFT expression contributes to the etiology of this disease. Here we report the molecular cloning and characterization of the human gene for SFT. FISH analysis maps the SFT gene to human chromosome 10q21. PCR analysis indicates 1000 nucleotides of intervening intron sequence near the 3' end of the coding region for SFT. Based on DNA sequence analysis of the additional 5' untranslated region obtained from the genomic clone, SFT lacks known metal-regulated transcriptional or translational control elements. These studies provide the basis for future elucidation of the mechanisms that control SFT expression in order to discover how this regulation is lost in hemochromatosis.
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PMID:Characterization and chromosomal mapping of the human gene for SFT, a stimulator of Fe transport. 991 97

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

Hemochromatosis is a common autosomal recessive condition found in the homozygous state in 1/200-1/400 people of northern-, central-, and western-European origin. It causes increased iron storage, which may lead to liver cirrhosis, liver cancer, heart disease, arthritis, and diabetes in many but not all affected adults, with a higher frequency in males. The condition is easily treated by repeated venesections without side effects but is frequently overlooked. Population screening of adults using iron indices alone or combined with DNA testing has therefore been recommended, but a consensus conference in 1997 recommended that such screening be deferred, owing to uncertainty regarding the extent of clinical disease that may develop in individuals detected by such programs. There was also concern that DNA screening results might be used for discrimination in insurance and occupational settings. Screening family members of patients with evidence of definite iron loading, however, is accepted by all observers. Because serious complications may be overlooked, a more aggressive stance toward case detection in the adult population has been advocated by some observers, realizing that unnecessary treatment might occur. Because additional information regarding the spectrum of clinical disease in homozygotes in now accumulating, a consensus conference in the near future is suggested to consider appropriate policies.
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PMID:Population screening in hereditary hemochromatosis. 1088 46

Hereditary hemochromatosis is the most commonly inherited autosomal recessive disorder. Hemochromatosis is a current or potential progression of abnormally high accumulations of iron in the liver. If left untreated, the condition can lead to chronic or irreversible hepatic fibrosis, cirrhosis, hepatocellular carcinoma, arthritis, and organ failure. Common signs and symptoms seen in the primary care setting include fatigue, weakness, abdominal pain, palpitations, skin pigmentation changes, and arthropathy, but any symptom associated with organ damage may be reported. Because prompt intervention can cease or reverse the debilitating effects of iron overload, prompt disease diagnosis and treatments are imperative.
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PMID:Detecting hereditary hemochromatosis. 1091 30

Genetic Hemochromatosis (GH) is a highly prevalent autosomal recessive disorder, which outcome has been dramatically improved by early phlebotomy. Attempts to screen for the disease, using biological and genetic approaches, are currently under evaluation. Diabetes mellitus often complicates GH. However, as it occurs late in the course of the disease, in most cases when cirrhosis is already present, its usefulness for the screening of GH seems reduced. Diabetes mellitus, when isolated, appears also as a poor predictor of hemochromatosis. Indeed, the risk of being carrier of the disease is not increased in diabetic patients compared with non diabetic sujects. This risk is however highly enhanced by the co-existence of cirrhosis. Thus, in the face of a newly diagnosed diabetes mellitus, the search for hemochromatosis must be performed only when it associates with cirrhosis or with other evocative clinical conditions.
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PMID:[Is diabetes mellitus a sufficient condition to suspect hemochromatosis?]. 1101 Dec 26

Hemochromatosis is one of the most frequent genetic diseases among the white populations, affecting one in three hundred persons. Its diagnosis has been radically transformed by the discovery of the HFE gene. In a given individual, the diagnosis can, from now on, be ascertained on the sole association of a plasma transferrin saturation (TS) over 45% and homozygosity for the C282Y mutation. Liver biopsy is only required to search for cirrhosis whenever there is hepatomegaly and/or serum ferritin >1000 ng/ml and/or elevated serum AST. Family screening is mandatory, primarily centered on the siblings. The treatment remains based on venesection therapy which improves many features of the disease (one of the most refractory, however, being the joint signs) and permits normal life expectancy provided the diagnosis is established prior to the development of cirrhosis or of insulin-dependent diabetes. In view of the prevalence, the non-invasive diagnosis, the spontaneous severity and the efficacy of a very simple therapy, hemochromatosis should benefit from population screening. This screening could be based, first, on the assessment of transferrin saturation, followed - when elevated - by the search for the C282Y mutation. The discovery of the HFE gene has also paved the road for the individualization of other types of iron overload syndromes which are not HFE-related.
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PMID:Clinical aspects of hemochromatosis. 1109 95


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