Non-HFE hemochromatosis

Center for Hemochromatosis and Hereditary Liver Diseases, Department of Internal Medicine, University of Modena and Reggio Emilia, Policlinico, Modena, Italy.
Seminars in Liver Disease (Impact Factor: 4.95). 12/2005; 25(4):450-60. DOI: 10.1055/s-2005-923316
Source: PubMed


The term "non-HFE hemochromatosis" (non-HFE HC) refers to several phenotypically similar but genetically distinct forms of hereditary hemochromatosis affecting individuals without pathogenic mutations of HFE. The involved genes are, sinsu strictu, transferrin receptor 2 (TfR2), hemojuvelin (HJV), and hepcidin (HAMP). Non-HFE HC share common pathogenic and clinical features with HFE HC. However, depending on the role of the affected gene in iron trafficking, the clinical onset may be earlier and phenotypic expressivity more severe than classic HC. Other forms of hereditary iron overload have distinct pathogenesis and phenotype. The most prevalent of these forms is "ferroportin disease," characterized by autosomal dominant trait, predominant reticuloendothelial cell iron overload, and mild organ damage. Non-HFE HC gene products, while responsible for rarer cases of HC as compared with HFE, are much more central than HFE in human iron homeostasis and understanding their function will greatly advance our comprehension of iron trafficking in health and disease.

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Available from: Antonello Pietrangelo, Oct 29, 2015
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    • "In conclusion, our case illustrates the poor prognosis of JH, in which delayed diagnosis and treatment resulted in severe cardiomyopathy and death in the fourth decade from heart failure and/or arrhythmia [9] [27]. In retrospect, an aggressive regimen of chelation may have yielded a better outcome. "
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    ABSTRACT: Juvenile hemochromatosis is a rare and severe form of hereditary hemochromatosis. We report the case of a 39-year-old female who presented with heart failure and cirrhosis from previously unrecognized juvenile hemochromatosis. This is the latest presentation described in the literature. An important clue to the diagnosis was a history of amenorrhea since the age of 20 that had never been investigated. The patient died of intractable heart failure two months after the initial presentation. Juvenile hemochromatosis should be suspected in a young patient with endocrine or cardiac manifestations. Early diagnosis is crucial since phlebotomy can improve the prognosis and delay or prevent progression to heart failure and cirrhosis.
    Full-text · Article · Sep 2013 · Case Reports in Medicine
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    • "Another genetic form of hereditary hemochromatosis results from mutation in ferroportin, reducing iron export from cells (Pietrangelo, 2004). Hereditary hemochromatosis can also result from mutations in Hepc, hemojuvelin (responsible for juvenile hemochromatosis), or TfR 2 (Pietrangelo, 2005; Nemeth and Ganz, 2006). In three cases with hereditary hemochromatosis, retinal abnormalities include drusen and iron in the peripapillary RPE, ciliary epithelium, and sclera (Roth and Foos, 1972). "
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    • "Types 1 and 3 HH are characterized by the classical HH phenotype, which includes parenchymal iron overload and the presence of HFE and TfR2 mutations, respectively. Type 2 HH is associated with the previously described phenotype of juvenile hemochromatosis and mutations in the HAMP and HJV genes, whereas type 4 HH is associated with heterogeneous clinical and laboratory findings of iron overload that are more pronounced in the reticuloendothelial system.13 "
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