FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 350:2383-2397 June 3, 2004 Number 23 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text PDF PDA Full Text Purchase this article Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

For much of the 20th century, hereditary hemochromatosis was regarded as a clinically and genetically unique entity. The classic findings on presentation — diabetes, bronze pigmentation of the skin, and cirrhosis — were first described in the 19th century, when the term "hemochromatosis" was first used^1,2,3; by 1935 it had become clear that the disease was hereditary and was caused by excess deposits of iron in the tissue.⁴ In the 1970s and 1980s, it was recognized as an autosomal recessive disorder linked to the region of the short arm of chromosome 6 encoding HLA-A*3 ,^5,6 and in 1996 "the . . . [Full Text of this Article]

Phenotypic and Genetic Features

Classic Hereditary Hemochromatosis

Genetic and Phenotypic Variations

The Genetic Cast: Major Players and Supporting Actors

Pathophysiology

Pathogenetic Models of HFE-Related Hereditary Hemochromatosis

Hepcidin: The Key Player in All Forms of Hereditary Hemochromatosis?

Diagnosis, Management, and Screening

Other Hereditary Iron-Overload Disorders

Conclusions

Source Information

From the Center for Hemochromatosis and Hereditary Liver Diseases, Department of Internal Medicine, University of Modena and Reggio Emilia Policlinico, Modena, Italy.

Address reprint requests to Dr. Pietrangelo at the Department of Medicine, University of Modena, Via del Pozzo 71, 41100 Modena, Italy, or at pietrangelo.antonello@unimore.it.

Related Letters:

Hereditary Hemochromatosis
Castiella A., Alustiza J. M., Artetxe J., Pietrangelo A.
Extract | Full Text | PDF  
N Engl J Med 2004; 351:1263-1264, Sep 16, 2004. Correspondence

This article has been cited by other articles:

• Whitington, P. F., Kelly, S. (2008). Outcome of Pregnancies at Risk for Neonatal Hemochromatosis Is Improved by Treatment With High-Dose Intravenous Immunoglobulin. Pediatrics 121: e1615-e1621 [Abstract] [Full Text]  
• Sendamarai, A. K., Ohgami, R. S., Fleming, M. D., Lawrence, C. M. (2008). Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle. Proc. Natl. Acad. Sci. USA 105: 7410-7415 [Abstract] [Full Text]  
• Kulaksiz, H., Fein, E., Redecker, P., Stremmel, W., Adler, G., Cetin, Y. (2008). Pancreatic {beta}-cells express hepcidin, an iron-uptake regulatory peptide. J Endocrinol 197: 241-249 [Abstract] [Full Text]  
• Aigner, E., Theurl, I., Theurl, M., Lederer, D., Haufe, H., Dietze, O., Strasser, M., Datz, C., Weiss, G. (2008). Pathways underlying iron accumulation in human nonalcoholic fatty liver disease. Am. J. Clin. Nutr. 87: 1374-1383 [Abstract] [Full Text]  
• Otogawa, K., Ogawa, T., Shiga, R., Nakatani, K., Ikeda, K., Nakajima, Y., Kawada, N. (2008). Attenuation of acute and chronic liver injury in rats by iron-deficient diet. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294: R311-R320 [Abstract] [Full Text]  
• Wallace, D. F., Summerville, L., Crampton, E. M., Subramaniam, V. N. (2008). Defective trafficking and localization of mutated transferrin receptor 2: implications for type 3 hereditary hemochromatosis. Am. J. Physiol. Cell Physiol. 294: C383-C390 [Abstract] [Full Text]  
• Allen, K. J., Gurrin, L. C., Constantine, C. C., Osborne, N. J., Delatycki, M. B., Nicoll, A. J., McLaren, C. E., Bahlo, M., Nisselle, A. E., Vulpe, C. D., Anderson, G. J., Southey, M. C., Giles, G. G., English, D. R., Hopper, J. L., Olynyk, J. K., Powell, L. W., Gertig, D. M. (2008). Iron-Overload-Related Disease in HFE Hereditary Hemochromatosis. NEJM 358: 221-230 [Abstract] [Full Text]  
• Equitani, F., Fernandez-Real, J. M., Menichella, G., Koch, M., Calvani, M., Nobili, V., Mingrone, G., Manco, M. (2008). Bloodletting Ameliorates Insulin Sensitivity and Secretion in Parallel to Reducing Liver Iron in Carriers of HFE Gene Mutations. Diabetes Care 31: 3-8 [Abstract] [Full Text]  
• Piperno, A., Girelli, D., Nemeth, E., Trombini, P., Bozzini, C., Poggiali, E., Phung, Y., Ganz, T., Camaschella, C. (2007). Blunted hepcidin response to oral iron challenge in HFE-related hemochromatosis. Blood 110: 4096-4100 [Abstract] [Full Text]  
• Hutchinson, C., Geissler, C. A, Powell, J. J, Bomford, A. (2007). Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut 56: 1291-1295 [Abstract] [Full Text]  
• Merle, U., Fein, E., Gehrke, S. G., Stremmel, W., Kulaksiz, H. (2007). The Iron Regulatory Peptide Hepcidin Is Expressed in the Heart and Regulated by Hypoxia and Inflammation. Endocrinology 148: 2663-2668 [Abstract] [Full Text]  
• Petrak, J., Myslivcova, D., Man, P., Cmejla, R., Cmejlova, J., Vyoral, D., Elleder, M., Vulpe, C. D. (2007). Proteomic analysis of hepatic iron overload in mice suggests dysregulation of urea cycle, impairment of fatty acid oxidation, and changes in the methylation cycle. Am. J. Physiol. Gastrointest. Liver Physiol. 292: G1490-G1498 [Abstract] [Full Text]  
• Zohn, I. E., De Domenico, I., Pollock, A., Ward, D. M., Goodman, J. F., Liang, X., Sanchez, A. J., Niswander, L., Kaplan, J. (2007). The flatiron mutation in mouse ferroportin acts as a dominant negative to cause ferroportin disease. Blood 109: 4174-4180 [Abstract] [Full Text]  
• Harris, E. L., McLaren, C. E., Reboussin, D. M., Gordeuk, V. R., Barton, J. C., Acton, R. T., McLaren, G. D., Vogt, T. M., Snively, B. M., Leiendecker-Foster, C., Holup, J. L., Passmore, L. V., Eckfeldt, J. H., Lin, E., Adams, P. C. (2007). Serum Ferritin and Transferrin Saturation in Asians and Pacific Islanders. Arch Intern Med 167: 722-726 [Abstract] [Full Text]  
• Ellervik, C., Tybjaerg-Hansen, A., Appleyard, M., Sillesen, H., Boysen, G., Nordestgaard, B. G. (2007). Hereditary hemochromatosis genotypes and risk of ischemic stroke. Neurology 68: 1025-1031 [Abstract] [Full Text]  
• Constante, M., Wang, D., Raymond, V.-A., Bilodeau, M., Santos, M. M. (2007). Repression of Repulsive Guidance Molecule C during Inflammation Is Independent of Hfe and Involves Tumor Necrosis Factor-{alpha}. Am. J. Pathol. 170: 497-504 [Abstract] [Full Text]  
• Sutedja, N. A., Sinke, R. J., Van Vught, P. W. J., Van der Linden, M. W., Wokke, J. H. J., Van Duijn, C. M., Njajou, O. T., Van der Schouw, Y. T., Veldink, J. H., Van den Berg, L. H. (2007). The Association Between H63D Mutations in HFE and Amyotrophic Lateral Sclerosis in a Dutch Population. Arch Neurol 64: 63-67 [Abstract] [Full Text]  
• Francucci, C. M., Gatti, C., Camilletti, A., Fiscaletti, P., Caudarella, R., Boscaro, M. (2007). Hypogonadism and Reduced Bone Mineral Density in Heterozygous H63D Mutation in the HFE Gene: An Unusual Presentation of Hereditary Hemochromatosis. J Androl 28: 21-26 [Full Text]  
• Chaudhury, C., Kim, J., Mehnaz, S., Wani, M. A., Oberyszyn, T. M., Bronson, C. L., Mohanty, S., Hayton, W. L., Robinson, J. M., Anderson, C. L. (2006). Accelerated Transferrin Degradation in HFE-Deficient Mice Is Associated with Increased Transferrin Saturation. J. Nutr. 136: 2993-2998 [Abstract] [Full Text]  
• Chung, R. T., Misdraji, J., Sahani, D. V. (2006). Case 33-2006 -- A 43-Year-Old Man with Diabetes, Hypogonadism, Cirrhosis, Arthralgias, and Fatigue. NEJM 355: 1812-1819 [Full Text]  
• Heinicke, K., Baum, O., Ogunshola, O. O., Vogel, J., Stallmach, T., Wolfer, D. P., Keller, S., Weber, K., Wagner, P. D., Gassmann, M., Djonov, V. (2006). Excessive erythrocytosis in adult mice overexpressing erythropoietin leads to hepatic, renal, neuronal, and muscular degeneration. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291: R947-R956 [Abstract] [Full Text]  
• Jeong, S. Y., David, S. (2006). Age-related changes in iron homeostasis and cell death in the cerebellum of ceruloplasmin-deficient mice.. J. Neurosci. 26: 9810-9819 [Abstract] [Full Text]  
• Whitlock, E. P., Garlitz, B. A., Harris, E. L., Beil, T. L., Smith, P. R. (2006). Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force.. ANN INTERN MED 145: 209-223 [Abstract] [Full Text]  
• Constante, M., Jiang, W., Wang, D., Raymond, V.-A., Bilodeau, M., Santos, M. M. (2006). Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 291: G229-G237 [Abstract] [Full Text]  
• Hertzberg, M, Neville, S, McDonald, D (2006). External quality assurance of molecular analysis of haemochromatosis gene mutations. J. Clin. Pathol. 59: 744-747 [Abstract] [Full Text]  
• Vantyghem, M.-C., Fajardy, I., Dhondt, F., Girardot, C., D'Herbomez, M., Danze, P.-M., Rousseaux, J., Wemeau, J.-L. (2006). Phenotype and HFE genotype in a population with abnormal iron markers recruited from an Endocrinology Department.. Eur J Endocrinol 154: 835-841 [Abstract] [Full Text]  
• McPherson, E. (2006). Genetic diagnosis and testing in clinical practice.. Clin Med Res 4: 123-129 [Abstract] [Full Text]  
• Swinkels, D. W., Janssen, M. C.H., Bergmans, J., Marx, J. J.M. (2006). Hereditary Hemochromatosis: Genetic Complexity and New Diagnostic Approaches. Clin. Chem. 52: 950-968 [Abstract] [Full Text]  
• Chlosta, S., Fishman, D. S., Harrington, L., Johnson, E. E., Knutson, M. D., Wessling-Resnick, M., Cherayil, B. J. (2006). The Iron Efflux Protein Ferroportin Regulates the Intracellular Growth of Salmonella enterica.. Infect. Immun. 74: 3065-3067 [Abstract] [Full Text]  
• Peltonen, L., Perola, M., Naukkarinen, J., Palotie, A. (2006). Lessons from studying monogenic disease for common disease.. Hum Mol Genet 15: R67-R74 [Full Text]  
• Donovan, A., Roy, C. N., Andrews, N. C. (2006). The Ins and Outs of Iron Homeostasis. Physiology 21: 115-123 [Abstract] [Full Text]  
• Pietrangelo, A (2006). Molecular insights into the pathogenesis of hereditary haemochromatosis.. Gut 55: 564-568 [Full Text]  
• McCune, C A, Ravine, D, Carter, K, Jackson, H A, Hutton, D, Hedderich, J, Krawczak, M, Worwood, M (2006). Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients. Gut 55: 554-562 [Abstract] [Full Text]  
• Ganz, T., Nemeth, E. (2006). Iron imports. IV. Hepcidin and regulation of body iron metabolism. Am. J. Physiol. Gastrointest. Liver Physiol. 290: G199-G203 [Abstract] [Full Text]  
• Brissot, P., de Bels, F. (2006). Current Approaches to the Management of Hemochromatosis. ASH Education Book 2006: 36-41 [Abstract] [Full Text]  
• Camaschella, C. (2005). Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders. Blood 106: 3710-3717 [Abstract] [Full Text]  
• Zhang, A.-S., West, A. P. Jr., Wyman, A. E., Bjorkman, P. J., Enns, C. A. (2005). Interaction of Hemojuvelin with Neogenin Results in Iron Accumulation in Human Embryonic Kidney 293 Cells. J. Biol. Chem. 280: 33885-33894 [Abstract] [Full Text]  
• Schmitt, B., Golub, R. M., Green, R. (2005). Screening Primary Care Patients for Hereditary Hemochromatosis with Transferrin Saturation and Serum Ferritin Level: Systematic Review for the American College of Physicians. ANN INTERN MED 143: 522-536 [Abstract] [Full Text]  
• Galy, B., Ferring, D., Minana, B., Bell, O., Janser, H. G., Muckenthaler, M., Schumann, K., Hentze, M. W. (2005). Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2). Blood 106: 2580-2589 [Abstract] [Full Text]  
• Fleming, R. E. (2005). The iron sensor: macrophage, hepatocyte, both?. Blood 106: 1893-1894 [Full Text]  
• Drakesmith, H., Schimanski, L. M., Ormerod, E., Merryweather-Clarke, A. T., Viprakasit, V., Edwards, J. P., Sweetland, E., Bastin, J. M., Cowley, D., Chinthammitr, Y., Robson, K. J. H., Townsend, A. R. M. (2005). Resistance to hepcidin is conferred by hemochromatosis-associated mutations of ferroportin. Blood 106: 1092-1097 [Abstract] [Full Text]  
• Chan, A. T., Ma, J., Tranah, G. J., Giovannucci, E. L., Rifai, N., Hunter, D. J., Fuchs, C. S. (2005). Hemochromatosis Gene Mutations, Body Iron Stores, Dietary Iron, and Risk of Colorectal Adenoma in Women. JNCI J Natl Cancer Inst 97: 917-926 [Abstract] [Full Text]  
• Adams, P. C., Reboussin, D. M., Leiendecker-Foster, C., Moses, G. C., McLaren, G. D., McLaren, C. E., Dawkins, F. W., Kasvosve, I., Acton, R. T., Barton, J. C., Zaccaro, D., Harris, E. L., Press, R., Chang, H., Eckfeldt, J. H. (2005). Comparison of the Unsaturated Iron-Binding Capacity with Transferrin Saturation as a Screening Test to Detect C282Y Homozygotes for Hemochromatosis in 101 168 Participants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Clin. Chem. 51: 1048-1052 [Full Text]  
• Fleming, R. E., Bacon, B. R. (2005). Orchestration of Iron Homeostasis. NEJM 352: 1741-1744 [Full Text]  
• Adams, P. C., Reboussin, D. M., Barton, J. C., McLaren, C. E., Eckfeldt, J. H., McLaren, G. D., Dawkins, F. W., Acton, R. T., Harris, E. L., Gordeuk, V. R., Leiendecker-Foster, C., Speechley, M., Snively, B. M., Holup, J. L., Thomson, E., Sholinsky, P., the Hemochromatosis and Iron Overload Screening (H, (2005). Hemochromatosis and Iron-Overload Screening in a Racially Diverse Population. NEJM 352: 1769-1778 [Abstract] [Full Text]  
• Tolosano, E., Fagoonee, S., Garuti, C., Valli, L., Andrews, N. C., Altruda, F., Pietrangelo, A. (2005). Haptoglobin modifies the hemochromatosis phenotype in mice. Blood 105: 3353-3355 [Abstract] [Full Text]  
• Lauth, X., Babon, J. J., Stannard, J. A., Singh, S., Nizet, V., Carlberg, J. M., Ostland, V. E., Pennington, M. W., Norton, R. S., Westerman, M. E. (2005). Bass Hepcidin Synthesis, Solution Structure, Antimicrobial Activities and Synergism, and in Vivo Hepatic Response to Bacterial Infections. J. Biol. Chem. 280: 9272-9282 [Abstract] [Full Text]  
• Kauwell, G. P. A. (2005). Emerging Concepts in Nutrigenomics: A Preview of What Is to Come. Nutr Clin Pract 20: 75-87 [Abstract] [Full Text]  
• Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., Ganz, T., Kaplan, J. (2004). Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization. Science 306: 2090-2093 [Abstract] [Full Text]  
• Ganz, T. (2004). Is TfR2 the iron sensor?. Blood 104: 3839-3840 [Full Text]  
• Johnson, M. B., Enns, C. A. (2004). Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 104: 4287-4293 [Abstract] [Full Text]  
• Krijt, J., Vokurka, M., Chang, K.-T., Necas, E. (2004). Expression of Rgmc, the murine ortholog of hemojuvelin gene, is modulated by development and inflammation, but not by iron status or erythropoietin. Blood 104: 4308-4310 [Abstract] [Full Text]  
• Castiella, A., Alustiza, J. M., Artetxe, J., Pietrangelo, A. (2004). Hereditary Hemochromatosis. NEJM 351: 1263-1264 [Full Text]