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Introduction to Supplement on Iron Overload, Public Health, and Genetics
- Adele L. Franks, MD; and
- James S. Marks, MD, MPH
- From Centers for Disease Control and Prevention; Atlanta, GA 30341. Note: This article is one of a series of articles comprising an Annals of Internal Medicine supplement entitled “Iron Overload, Public Health, and Genetics.” To view a complete list of the articles included in this supplement, please view its Table of Contents. Requests for Reprints: Adele L. Franks MD, Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Mailstop K-24, 4770 Buford Highway, Atlanta, GA 30341; e-mail, alf1{at}cdc.gov. Current Author Addresses: Dr. Franks: Division of Nutrition and Physical Activity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Mailstop K-24, 4770 Buford Highway, Atlanta, GA 30341. Dr. Marks: Office of the Director, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Mailstop K-40, 4770 Buford Highway, Atlanta, GA 30341.
The past few years have witnessed a growing awareness that iron overload diseases are not as rare as was previously believed. One particular form of primary iron overload disease-hereditary hemochromatosis-has received increasing attention because it seems to be more common than many other serious genetic disorders [1], it can be detected before clinical symptoms develop [1, 2], and its complications can be safely prevented through the early use of therapeutic phlebotomy [3]. For these reasons, it has been suggested that phenotypic screening for hereditary hemochromatosis should be a routine part of health care for adults [4, 5]. Efforts to estimate the cost-effectiveness of such screening have used available information on disease expression, costs of specific disease manifestations, and existing laboratory tests and have concluded that screening can indeed be cost-effective ([6, 7]; Messonier M. Personal communication). A group of experts convened by the Centers for Disease Control and Prevention [CDC] in February 1996 considered 1) whether screening for hereditary hemochromatosis was warranted and 2) the relative merits of the biochemical laboratory tests of iron status that might be useful for screening. The group favored movement toward routine screening for all adults. Yet, much remains to be learned about the penetrance and expressivity of hereditary hemochromatosis (and, thus, the burden of disease that may be preventable) and about the patient age and disease stage at which detection is most beneficial.
Hereditary hemochromatosis has long been recognized as an autosomal recessive inherited condition that is believed to be linked to the HLA region on chromosome 6 [8]. The recent identification [9] of two genetic mutations in this location that may account for most cases of hereditary hemochromatosis in white persons in the United States opens new possibilities for earlier detection. With a valid genetic test, it will be possible to identify persons with hereditary hemochromatosis even before abnormal serum iron status is detectable and to follow them carefully so that treatment can begin before iron accumulation occurs. Nonetheless, the possibility of widespread screening for a genetic disorder introduces new complexities for a society that is not yet accustomed to the genetic testing of adults on a large scale and is suspicious of the potential misuse of genetic information. In this context, meticulous preparation for widespread screening (whether phenotypic or genotypic) for hereditary hemochromatosis is essential to ensure a favorable response from the public, health care practitioners, health care purchasers and insurers, laboratories, and organized systems of care. Given the expectation that in the future we will have the technical ability to test for many genetically influenced conditions, efforts to educate and prepare the public and professional sectors of society for the therapeutic, social, and legal implications of genetic screening could have an impact that goes far beyond applications to hereditary hemochromatosis.
This supplement contains the highlights of a 3-day meeting sponsored by the CDC in March 1997. Experts from many fields addressed the challenging questions that must be answered before population screening for hereditary hemochromatosis can be recommended. Persons with diverse backgrounds from across the United States and around the world were invited to participate; the participants included physicians, geneticists, ethicists, policymakers, public health experts, laboratory scientists, and members of patient advocacy groups. Physicians included specialists in the care of hereditary hemochromatosis (such as hepatologists, gastroenterologists, and hematologists) and primary care physicians, who are usually the first to see patients with iron overload.
The meeting covered a broad array of issues, many of which are discussed in this supplement. The first day of the conference was co-sponsored by the National Human Genome Research Institute of the National Institutes of Health; on this day, hereditary hemochromatosis was used as a case study to focus on elucidation of the clinical, public health, ethical, legal, and social implications of genetic screening. The second and third days of the conference brought closer scrutiny to the issues identified by the expert panel convened by the CDC in 1996. Presentations covered the laboratory and epidemiologic characteristics of candidate laboratory tests for hereditary hemochromatosis screening; cost-effectiveness; the relation between hereditary hemochromatosis genotype and phenotype; types of iron overload that may not be detectable with currently available molecular or biochemical tests; diagnosis, management, and surveillance for hereditary hemochromatosis; and the need for public and provider education about hereditary hemochromatosis. In addition, four working groups met to discuss and make recommendations on the management of hereditary hemochromatosis, the identification of high-priority research questions that can be addressed through applied research, the creation of a surveillance system for hereditary hemochromatosis, and the formulation of programs to help physicians recognize opportunities for early detection of disease.
Readers should note that the nomenclature for hereditary hemochromatosis and the stages of primary iron overload have not been standardized in the medical literature to date. Hereditary hemochromatosis is an autosomal recessive condition associated with primary overabsorption of iron from the gastrointestinal tract. When iron accumulation leads to abnormal signs or symptoms, hereditary hemochromatosis is considered a disease; in the absence of abnormal serum or tissue iron status, it is considered a condition or a predisposition to disease. The authors of the papers presented here graciously tried to adhere to this convention, but it must be acknowledged that no such consistency can be expected in other publications. As our understanding of the progression from predisposition to expression of diseases improves, we may need a new classification system to denote stages along this continuum for many conditions.
This supplement contains reports based on presentations held during conference plenary sessions as well as summary reports based on discussions of the working groups. We hope that these articles will stimulate further discussion about hereditary hemochromatosis and the possibility of reducing unnecessary morbidity and mortality resulting from this disease and, ultimately, from other genetic disorders.
- Copyright ©2004 by the American College of Physicians
