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Contributors
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- By Graeme J.M. Alexander, Heung Bae Kim, Michael Burch, Andrew J. Butler, Tanveer Butt, Roy Calne, Edward Cantu, Robert B. Colvin, Paul Corris, Charles Crawley, Hiroshi Date, Francis L. Delmonico, Bimalangshu R. Dey, Kate Drummond, John Dunning, John D. Firth, John Forsythe, Simon M. Gabe, Robert S. Gaston, William Gelson, Paul Gibbs, Alex Gimson, Leo C. Ginns, Samuel Goldfarb, Ryoichi Goto, Walter K. Graham, Simon J.F. Harper, Koji Hashimoto, David G. Healy, Hassan N. Ibrahim, David Ip, Fadi G. Issa, Neville V. Jamieson, David P. Jenkins, Dixon B. Kaufman, Kiran K. Khush, Heung Bae Kim, Andrew A. Klein, John Klinck, Camille Nelson Kotton, Vineeta Kumar, Yael B. Kushner, D. Frank. P. Larkin, Clive J. Lewis, Yvonne H. Luo, Richard S. Luskin, Ernest I. Mandel, James F. Markmann, Lorna Marson, Arthur J. Matas, Mandeep R. Mehra, Stephen J. Middleton, Giorgina Mieli-Vergani, Charles Miller, Sharon Mulroy, Faruk Özalp, Can Ozturk, Jayan Parameshwar, J.S. Parmar, Hari K. Parthasarathy, Nick Pritchard, Cristiano Quintini, Axel O. Rahmel, Chris J. Rudge, Stephan V.B. Schueler, Maria Siemionow, Jacob Simmonds, Peter Slinger, Thomas R. Spitzer, Stuart C. Sweet, Nina E. Tolkoff-Rubin, Steven S.L. Tsui, Khashayar Vakili, R.V. Venkateswaran, Hector Vilca-Melendez, Vladimir Vinarsky, Kathryn J. Wood, Heidi Yeh, David W. Zaas, Jonathan G. Zaroff
- Edited by Andrew A. Klein, Clive J. Lewis, Joren C. Madsen
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- Book:
- Organ Transplantation
- Published online:
- 07 September 2011
- Print publication:
- 11 August 2011, pp vii-x
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29 - Estimate of the frequency of morbid complications of hemochromatosis
- from Part V - Complications of iron overload
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- By Corwin Q. Edwards, Departments of Medicine,University of Utah College of Medicine and LDS Hospital, Salt Lake City, Utah, USA, Linda M. Griffen, Departments of Medicine,University of Utah College of Medicine, Zaneta J. Bulaj, Departments of Medicine,University of Utah College of Medicine, Richard S. Ajioka, Departments of Medicine,University of Utah College of Medicine, James P. Kushner, Departments of Medicine,University of Utah College of Medicine
- Edited by James C. Barton, Southern Iron Disorders Center, Alabama, Corwin Q. Edwards, University of Utah
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- Book:
- Hemochromatosis
- Published online:
- 05 August 2011
- Print publication:
- 13 January 2000, pp 312-317
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Summary
Introduction
There are many descriptions of the organ damage associated with late-stage hemochromatosis. The frequency of some of the symptoms of illness, abnormal physical examination findings and laboratory abnormalities in hemochromatosis patients who were identified in different ways are summarized in Table 29.1. The purpose of this chapter is to compare the morbidity of hemochromatosis in homozygotes who were not identified due to illness and in probands who were identified due to illness.
Selection bias in identification of hemochromatosis homozygotes
There is a strong ascertainment bias in the identification of hemochromatosis probands. The ascertainment of probands who seek medical attention due to illness is biased for the presence of morbidity. Those who are found to have hemochromatosis only because they participated in a screening study have an ascertainment bias for good health. A comparison of differences in the morbidity among groups of probands whose ascertainment was biased either for illness or for good health appears in Tables 29.2 and 29.3. The great differences in the morbidity among groups of sick probands and probands who were identified during screening clearly demonstrate the effect of ascertainment bias on the presentation of hemochromatosis.
The diagnosis of hemochromatosis is established much more frequently among men than in women. This also represents an ascertainment bias explained, in part, by differences in the amount of iron that accumulates in male and in female homozygotes. Male homozygotes, as a group, have a greater body iron burden than female homozygotes. Normal women may lose 10–15 grams of iron during their lifetime due to menstruation and pregnancies.
2 - Hemochromatosis: a genetic definition
- from Part I - Introduction to hemochromatosis
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- By Corwin Q. Edwards, Departments of Medicine, University of Utah College of Medicine; LDS Hospital, Salt Lake City, Utah, USA, Richard S. Ajioka, Departments of Medicine, University of Utah College of Medicine, James P. Kushner, Departments of Medicine, University of Utah College of Medicine
- Edited by James C. Barton, Southern Iron Disorders Center, Alabama, Corwin Q. Edwards, University of Utah
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- Book:
- Hemochromatosis
- Published online:
- 05 August 2011
- Print publication:
- 13 January 2000, pp 8-12
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Summary
Early definitions of hemochromatosis
The definition of hemochromatosis, a disorder that causes iron overload, has undergone a great metamorphosis from the initial description of bronze diabetes in 1865 to the identification of a hemochromatosis gene in 1996. The original definition was a simple description of the two abnormalities that were noted at the time: skin pigmentation and diabetes mellitus. Six years later, the definition was modified to include the observation of iron deposition in a cirrhotic liver. In 1889, von Recklinghausen advanced the definition to emphasize the presumed pathophysiologic abnormality: iron from circulating blood accumulated in and caused pigmentation of the liver.
Definitions in the twentieth century
During most of the twentieth century, hemochromatosis was considered to be an idiopathic disorder. Some authors included in the definition a statement about possible causes of iron overload, such as an unidentified environmental effect, disordered copper metabolism, or alcohol abuse. Sheldon considered the possibility that hemochromatosis is an inborn error of metabolism. Prior to 1949, hemochromatosis was regarded as untreatable, because there was no known reliable therapy for iron overload or its complications. The first reports of phlebotomy therapy for hemochromatosis appeared at mid-century. By 1955, hemochromatosis was believed to be a rare idiopathic disorder of iron metabolism, primarily of middle-aged men, that caused heavy iron overload. Signs and symptoms included grey-green skin pigmentation, hepatomegaly, splenomegaly, ascites, diabetes mellitus, hypogonadism, heart failure, hepatic cirrhosis, and hepatocellular carcinoma.
39 - The iron phenotype of hemochromatosis heterozygotes
- from Part VIII - Hemochromatosis heterozygotes
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- By Corwin Q. Edwards, Departments of Medicine, University of Utah College of Medicine; LDS Hospital, Salt Lake City,Utah, USA, Linda M. Griffen, Departments of Medicine, University of Utah College of Medicine, Zaneta J. Bulaj, Departments of Medicine, University of Utah College of Medicine, Richard S. Ajioka, Departments of Medicine, University of Utah College of Medicine, James P. Kushner, Departments of Medicine, University of Utah College of Medicine
- Edited by James C. Barton, Southern Iron Disorders Center, Alabama, Corwin Q. Edwards, University of Utah
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- Book:
- Hemochromatosis
- Published online:
- 05 August 2011
- Print publication:
- 13 January 2000, pp 411-418
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Summary
Introduction
The issue whether hemochromatosis heterozygotes develop disease-related morbidity is controversial. Because iron is the source of the organ damage in hemochromatosis, heterozygotes would have to become iron loaded for complications to occur. By definition, heterozygotes have one-half of the hemochromatosis genotype, possessing one mutant and one wild-type allele. Does the presence of one-half of the hemochromatosis gene product result in the expression of one-half of the homozygous phenotype? Most importantly, do hemochromatosis heterozygotes develop disease-related morbidity?
Even if heterozygotes do not develop an intermediate hemochromatosis phenotype, they may be at increased risk of morbidity if other disorders, such as porphyria cutanea tarda, hereditary spherocytosis, or beta-thalassemia minor are present. Does excess iron in hemochromatosis heterozygotes confer upon them an increased risk to develop cancer or coronary artery disease? Answers to some of these intriguing questions will be considered in the current chapter and will be considered in additional detail in other chapters of this book.
Identification of heterozygotes
Hemochromatosis is tightly linked to the HLA Class I region on chromosome 6. It is therefore possible to assign a hemochromatosis genotype within a pedigree based on HLA-A serotypes shared with the proband. Due to autosomal recessive transmission of hemochromatosis, parents and offspring of a proband are, at least, obligate heterozygotes. This chapter describes the iron phenotype of members of pedigrees who have been assigned the heterozygous genotype based on half-HLA-identity with a homozygous proband.