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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    • "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.
    Case Reports in Medicine 09/2013; 2013:875093. DOI:10.1155/2013/875093
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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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    ABSTRACT: Iron is essential for life, but excess iron can be toxic. As a potent free radical creator, iron generates hydroxyl radicals leading to significant oxidative stress. Since iron is not excreted from the body, it accumulates with age in tissues, including the retina, predisposing to age-related oxidative insult. Both hereditary and acquired retinal diseases are associated with increased iron levels. For example, retinal degenerations have been found in hereditary iron overload disorders, like aceruloplasminemia, Friedreich's ataxia, and pantothenate kinase-associated neurodegeneration. Similarly, mice with targeted mutation of the iron exporter ceruloplasmin and its homolog hephaestin showed age-related retinal iron accumulation and retinal degeneration with features resembling human age-related macular degeneration (AMD). Post mortem AMD eyes have increased levels of iron in retina compared to age-matched healthy donors. Iron accumulation in AMD is likely to result, in part, from inflammation, hypoxia, and oxidative stress, all of which can cause iron dysregulation. Fortunately, it has been demonstrated by in vitro and in vivo studies that iron in the retinal pigment epithelium (RPE) and retina is chelatable. Iron chelation protects photoreceptors and retinal pigment epithelial cells (RPE) in a variety of mouse models. This has therapeutic potential for diminishing iron-induced oxidative damage to prevent or treat AMD.
    Frontiers in Aging Neuroscience 06/2013; 5:24. DOI:10.3389/fnagi.2013.00024 · 4.00 Impact Factor
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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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    ABSTRACT: Approximately one-half of Brazilian patients with hereditary hemochromatosis (HH) are neither homozygous for the C282Y mutation nor compound heterozygous for the H63D and C282Y mutations that are associated with HH in Caucasians. Other mutations have been described in the HFE gene as well as in genes involved in iron metabolism, such as transferrin receptor 2 (TfR2) and ferroportin 1 (SCL40A1). To evaluate the role of HFE, TfR2 and SCL40A1 mutations in Brazilian subjects with HH. Nineteen male subjects (median age 42 [range: 20-72] years) with HH were evaluated using the Haemochromatosis StripAssay A. This assay is capable of detecting twelve HFE mutations, which are V53M, V59M, H63D, H63H, S65C, Q127H, P160delC, E168Q, E168X, W169X, C282Y and Q283, four TfR2 mutations, which are E60X, M172K, Y250X, AVAQ594-597del, and two SCL40A1 mutations, which are N144H and V162del. In our cohort, nine (47%) patients were homozygous for the C282Y mutation, two (11%) were heterozygous for the H63D mutation, and one each (5%) was either heterozygous for C282Y or compound heterozygous for C282Y and H63D. No other mutations in the HFE, TfR2 or SCL40A1 genes were observed in the studied patients. One-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of HH in Brazil.
    Clinics (São Paulo, Brazil) 09/2009; 64(9):837-41. DOI:10.1590/S1807-59322009000900003 · 1.19 Impact Factor
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