Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hereditary hemochromatosis (HH) is a common autosomal recessive disease characterized by increased iron absorption and progressive iron storage that results in damage to major organs in the body. Recently, a candidate gene for HH called HFE encoding a major histocompatibility complex class I-like protein was identified by positional cloning. Nearly 90% of Caucasian HH patients have been found to be homozygous for the same mutation (C282Y) in the HFE gene. To test the hypothesis that the HFE gene is involved in regulation of iron homeostasis, we studied the effects of a targeted disruption of the murine homologue of the HFE gene. The HFE-deficient mice showed profound differences in parameters of iron homeostasis. Even on a standard diet, by 10 weeks of age, fasting transferrin saturation was significantly elevated compared with normal littermates (96 +/- 5% vs. 77 +/- 3%, P < 0.007), and hepatic iron concentration was 8-fold higher than that of wild-type littermates (2,071 +/- 450 vs. 255 +/- 23 microg/g dry wt, P < 0.002). Stainable hepatic iron in the HFE mutant mice was predominantly in hepatocytes in a periportal distribution. Iron concentrations in spleen, heart, and kidney were not significantly different. Erythroid parameters were normal, indicating that the anemia did not contribute to the increased iron storage. This study shows that the HFE protein is involved in the regulation of iron homeostasis and that mutations in this gene are responsible for HH. The knockout mouse model of HH will facilitate investigation into the pathogenesis of increased iron accumulation in HH and provide opportunities to evaluate therapeutic strategies for prevention or correction of iron overload.
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PMID:HFE gene knockout produces mouse model of hereditary hemochromatosis. 948 31

When suspecting an iron overload condition, the transferrin saturation levels should be determined. Levels higher than 45% and serum ferritin in men and postmenopausal women exceeding 200 microg/l confirm the iron overload. Afterwards, the HFE protein genotype should be determined. If it is C282Y or C282Y/H63D, the diagnosis of hereditary hemochromatosis can be accepted as the cause of the iron overload. In the absence of said genotypes, the overload is secondary or not related to the HFE protein. In hereditary hemochromatosis, the degree of iron overload and organic lesions must be established. Liver biopsies are very useful for obtaining said information and for the first case, the determination of serum ferritin is very useful. When less than 1000 microg/l, normal transaminases and no hepatomegalies, a treatment can be started without the need for a liver biopsy. In absence of anemia, the treatment is based on phlebotomies, 400-500 ml a week until obtaining depletion of excess iron. In presence of anemia, the treatment is based on chelating agents, preferably subcutaneous administered 8 hours a day.
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PMID:Strategy for diagnosis and management in iron overload. 1282 22

In chronic hemodialysis patients, a disruption in iron metabolism ranging from absolute to functional deficiency, with compartmentalization of this metal into macrophages, is often observed. Chronic inflammation indeed often causes an upregulation of the iron hormone hepcidin, thereby reducing iron absorption and availability to the erythron. We systematically reviewed the literature on the role of genetic risk factors on iron metabolism in hemodialysis. In this setting, mutations in the HFE gene of hereditary hemochromatosis may confer an adaptive benefit by decreasing hepcidin release, thus improving iron availability to erythropoiesis, anemia control, and the response to erythropoiesis stimulating agents and iron itself, and reducing the side effects of these therapies. The HFE protein together with Transferrin receptor-2 may also have a direct role on erythroid differentiation and iron uptake in erythroid cells. In addition, other genetic determinants of iron status, such as variants in Matriptase-2 (TMPRSS6), have been shown to influence iron metabolism in chronic hemodialysis patients, most likely acting through hepcidin regulation. Although data must be confirmed in larger prospective studies, this favorable shift in iron metabolism balance possibly results in reduced mortality, in particular because of cardiovascular and infective diseases. Further genetic studies may offer a valuable tool to test these hypotheses and guide personalized clinical management and the research of new therapies.
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PMID:HFE mutations and iron in hemodialysis patients. 2829 12