Hereditary hemochromatosis: A prevalent disorder of iron metabolism with an elusive etiology
Abstract
Hereditary hemochromatosis is a prevalent inherited disorder with an estimated frequency of homozygosity of 0.2 to 0.45% in Caucasians. The disease is characterized by progressive iron overload until a massive accumulation of body iron occurs. Undetected, the disorder eventually can produce either cirrhosis, diabetes mellitus, cardiac disease, arthritis, or hepatocellular carcinoma or a combination of these manifestations. Early diagnosis and treatment prevents organ damage and normalizes life expectancy. Screening studies to detect hemochromatosis are most effectively accomplished by measurement of the serum iron and total iron binding capacity. Treatment is most effectively performed by frequent phlebotomy until body stores are empty and then 3 to 4 times yearly for life. The basic defect of hemochromatosis appears to increase iron absorption, decrease iron excretion, and produce preferential deposit of iron in hepatic parenchymal cells rather than Kupffer cells. The genetic abnormality of hemochromatosis is located on chromosome 6 in close association with the gene for HLA antigens. Recent speculation postulates that tumor necrosis factor may be involved in the etiology of this disease because of its location on chromosome 6 and its effect upon iron transport. © 1994 Wiley‐Liss, Inc.
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IRP1-knockout mice survived with insignificant effects on iron homeostasis in kidney and brown fat.
“IRP1-knockout mice survived with insignificant effects on iron homeostasis in kidney and brown fat that highly express IRP1 (55, 200).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [55]
Cites
Receptor-mediated endocytosis of transferrin in K562 cells.
Klausner, R. D., van Renswoude, J., Ashwell, G., Kempf, C., Schechter, A. N., Dean, A., & Bridges, K. R. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32481-5 · Cited by 563 · see citing works
Iron absorption. I. Factors influencing absorption.
Th, B., Pirzio-Biroli, G., & Ca, F. (1958) · PubMed · Cited by 253 · see citing works
Conrad, M. E., & Umbreit, J. N. (1993) · American Journal of Hematology · doi:10.1002/ajh.2830420114 · Cited by 138 · see citing works
Self-citationExpression of hemochromatosis in homozygous subjects
Powell, L. W., SUMMERS, K. M., PHILLIP G. BOARD, et al. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)91100-k · Cited by 111 · see citing works
A role for mucin in the absorption of inorganic iron and other metal cations
Conrad, M. E., Umbreit, J. N., & MOORE, E. G. (1991) · Gastroenterology · doi:10.1016/0016-5085(91)90592-9 · Cited by 103 · see citing works
Self-citationImprovement in chronic hepatocerebral degeneration following liver transplantation
Powell, E. E., Pender, M. P., Chalk, J. B., et al. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90036-z · Cited by 94 · see citing works
Parmley, R. T., Barton, J. C., & Conrad, M. E. (1985) · British Journal of Haematology · doi:10.1111/j.1365-2141.1985.tb07388.x · Cited by 91 · see citing works
Self-citationHeredity of idiopathic haemochromatosis: A study of 106 families
Simon, M., Alexandre, J.-L., Bourel, M., Marec, B. L., & Scordia, C. (1977) · Clinical Genetics · doi:10.1111/j.1399-0004.1977.tb01324.x · Cited by 90 · see citing works
Conrad, M. E., Umbreit, J. N., MOORE, E. G., et al. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)34117-1 · Cited by 86 · see citing works
Self-citationGenetic and phenotypic expression of hemochromatosis in Canadians.
St, B., Ghent, C. N., Pr, F., et al. (1983) · PubMed · Cited by 84 · see citing works
Muir, W. A., Hopfer, U., & King, M. E. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42930-9 · Cited by 83 · see citing works
Bassett, M. L., Halliday, J. W., & Powell, L. W. (1981) · Hepatology · doi:10.1002/hep.1840010206 · Cited by 80 · see citing works
Fineberg, R. A., & Greenberg, D. M. (1955) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)70947-2 · Cited by 79 · see citing works
Transferrin receptor distribution and regulation in the rat small intestine
Anderson, G. J., Powell, L. W., & Halliday, J. W. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90276-7 · Cited by 79 · see citing works
Function of integrin in duodenal mucosal uptake of iron
Conrad, M., Jn, U., Peterson, R., Moore, E., & Harper, K. (1993) · Blood · doi:10.1182/blood.v81.2.517.517 · Cited by 77 · see citing works
Self-citationGordeuk, V., Ballou, S. P., Lozanski, G., & Brittenham, G. (1992) · Blood · doi:10.1182/blood.v79.7.1855.1855 · Cited by 74 · see citing works
The Rate of Iron Accumulation in Iron Storage Disease
Crosby, W. H., Conrad, M. E., & Wheby, M. S. (1963) · Blood · doi:10.1182/blood.v22.4.429.429 · Cited by 73 · see citing works
Self-citationEffect of endotoxin on iron absorption
Cortell, S., & Conrad, M. E. (1967) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1967.213.1.43 · Cited by 69 · see citing works
Self-citationNewly identified iron-binding protein in human duodenal mucosa
Conrad, M., Jn, U., Moore, E., et al. (1992) · Blood · doi:10.1182/blood.v79.1.244.244 · Cited by 63 · see citing works
Self-citationRat duodenal iron-binding protein mobilferrin is a homologue of calreticulin
Conrad, M. E., Umbreit, J. N., & MOORE, E. G. (1993) · Gastroenterology · doi:10.1016/0016-5085(93)90648-v · Cited by 60 · see citing works
Self-citationSmall intestinal regulation of iron absorption in the rat.
Me, C., Rt, P., & Osterloh, K. R. S. (1987) · PubMed · Cited by 59 · see citing works
Portacaval Anastomosis and Hepatic Hemosiderin Deposition: A Prospective, Controlled Investigation
Conn, H. O. (1972) · Gastroenterology · doi:10.1016/s0016-5085(72)80010-6 · Cited by 56 · see citing works
Alternate iron transport pathway. Mobilferrin and integrin in K562 cells.
Conrad, M. E., Umbreit, J. N., Moore, E., Uzel, C., & Berry, M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)37263-0 · Cited by 53 · see citing works
Self-citationMapping the locus for hereditary hemochromatosis: localization between HLA-B and HLA-A.
Edwards, C. Q., Griffen, L. M., Dadone, M. M., et al. (1986) · PubMed · Cited by 52 · see citing works
The Treatment of Hemochromatosis by Phlebotomy
Weintraub, L. R., Conrad, M. E., & Crosby, W. H. (1966) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)33106-6 · Cited by 51 · see citing works
Self-citationYaouanq, J., Périchon, M., Chorney, M. J., Pontarotti, P., Treut, A. L., Kahloun, A. E., Mauvieux, V., Blayau, M., Jouanolle, A., & Chauvel, B. (1994) · PubMed Central · Cited by 48 · see citing works
Regulation of iron absorption: proteins involved in duodenal mucosal uptake and transport.
Conrad, M. E., Umbreit, J. N., & Moore, E. (1993) · Journal of the American College of Nutrition · doi:10.1080/07315724.1993.10718365 · Cited by 43 · see citing works
Self-citationThe Relative Importance of the Duodenum in the Intestinal Absorption of Iron
Duthie, H. L. (1964) · British Journal of Haematology · doi:10.1111/j.1365-2141.1964.tb00678.x · Cited by 39 · see citing works
Gasparini, P., Borgato, L., Piperno, A., et al. (1993) · Human Molecular Genetics · doi:10.1093/hmg/2.5.571 · Cited by 37 · see citing works
Normal Iron Absorption in Hypertransferrinaemic Rats
Schade, S. G., Bernier, G. M., & Conrad, M. E. (1969) · British Journal of Haematology · doi:10.1111/j.1365-2141.1969.tb01358.x · Cited by 30 · see citing works
Self-citationThe regulation of iron absorption. I. A search for humoral factors.
BEUTLER, E., & Buttenwieser, E. (1960) · PubMed · Cited by 28 · see citing works
Genetics of Hemochromatosis: HLA Association and Mode of Inheritancea
Simon, M., Yaouanq, J., Fauchet, R., et al. (1988) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1988.tb55488.x · Cited by 28 · see citing works
Gruen, J. R., Goei, V. L., SUMMERS, K. M., Capossela, A., Powell, L. W., Halliday, J. W., Zoghbi, H. Y., Shukla, H., & Weissman, S. M. (1992) · Genomics · doi:10.1016/s0888-7543(05)80211-3 · Cited by 25 · see citing works
Problems in the measurement of iron binding capacity in serum
Williams, H. L., & Conrad, M. E. (1972) · Clinica Chimica Acta · doi:10.1016/0009-8981(72)90424-x · Cited by 18 · see citing works
Self-citationHumoral Regulation of Iron Absorption
Conrad, M. E., & Colonel, M. C. (1969) · Gastroenterology · doi:10.1016/s0016-5085(19)33941-1 · Cited by 17 · see citing works
Self-citationPrevalence of the Hemochromatosis Gene
Weber, C. J., Reemtsma, K., Greenwood, M. R., et al. (1980) · New England Journal of Medicine · doi:10.1056/nejm198003203021221 · Cited by 10 · see citing works
Edwards, C. Q., Griffen, L. M., & Kushner, J. P. (1991) · Hospital Practice · doi:10.1080/21548331.1991.11704282 · Cited by 10 · see citing works
An STS in the human TNF locus located at 6p21.3
Udalova, I. A., Kuprash, D. V., Turetskaya, R. L., et al. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.17.4784 · Cited by 6 · see citing works
SELECTIVE ADVANTAGE FOR FEMALES WITH h‐ALLELE?: To the Editor:
Janković, G. M., Čolović, M. D., Petrović, M., et al. (1989) · European Journal Of Haematology · doi:10.1111/j.1600-0609.1989.tb00296.x · Cited by 3 · see citing works
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Intracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526 · see citing works
- Authors
- Conrad, M. E., Umbreit, J. N., Moore, E. G., & Parmley, R. T.
- Affiliations
- University of South Alabama (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Conrad, Marcel E.
- Venue
- American Journal of Hematology
- Publisher
- Wiley
- Published
- 1994-11
- Volume
- 47
- Issue
- 3
- Pages
- 218-224
- ISSN
- 0361-8609 (ISSN-L)
- 1096-8652
- OpenAlex
- W2053189818
- Cited by
- 18
- References
- 39
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Hematology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk036112-07)
- National Institute of Diabetes and Digestive and Kidney Diseases (2 R01 DK36112)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- hereditary hemochromatosis, iron overload, iron metabolism, iron absorption, iron excretion, liver iron deposition, HLA antigens, chromosome 6, TNF-α, phlebotomy, serum iron, total iron binding capacity, screening, liver cirrhosis, hepatocellular carcinoma, diabetes mellitus
- MeSH terms
- Family Health, Hemochromatosis, Humans, Iron
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