A Survey of 2,851 Patients with Hemochromatosis: Symptoms and Response to Treatment Sharon M. McDonnell, MD, MPH, Ben L. Preston, BS, Sandy A. Jewell, MS, MPA, James C. Barton, MD, Corwin Q. Edwards, MD, Paul C. Adams, MD, Ray Yip, MD, MPH PURPOSE: Hemochromatosis is a genetic disorder of iron ab- sorption that affects 5 per 1,000 persons and is associated with reduced health and quality of life. We sought to determine the type and frequency of symptoms that patients experienced be- fore the diagnosis and the treatments that they received. METHODS: We mailed a questionnaire to 3,562 patients with hemochromatosis who were located using patient advocacy groups, physicians, blood centers, newsletters, and the Internet. RESULTS: Of the 2,851 respondents, 99% were white and 62% were men. Circumstances that led to diagnosis of hemochroma- tosis included symptoms (35%), an abnormal laboratory test (45%), and diagnosis of a family member with hemochromato- sis (20%). The mean ( SD) age of symptom onset was 41  14 years. Symptoms had been present for an average of 10  10 years before the diagnosis was made. Among the 58% of pa- tients with symptoms, 65% had physician-diagnosed arthritis and 52% had liver disease. The most common and troublesome symptoms were extreme fatigue (46%), arthralgia (44%), and loss of libido (26%). Physician instructions to patients included treatment with phlebotomy (90%), testing family members (75%), and avoiding iron supplements (65%). CONCLUSIONS: The diagnosis of hemochromatosis in most patients was delayed. Physician education is needed to increase the detection of patients with the disease and to improve its management. Am J Med. 1999;106:619 – 624. 1999 by Ex- cerpta Medica, Inc. H emochromatosis is an autosomal recessive dis- order of iron regulation that was first recognized as a clinical syndrome 100 years ago (1,2). It results in excess intestinal absorption and cellular depo- sition of iron (3,4). Unless removed by therapeutic phle- botomy, the excess iron accumulates, causing tissue dam- age that may be fatal. Clinical conditions associated with hemochromatosis include severe fatigue, arthritis, and arthropathy; hypopituitarism; hypogonadism; diabetes mellitus; cirrhosis; hepatocellular carcinoma; and cardio- myopathy (4,5). Hemochromatosis was previously estimated to affect 1 in 20,000 persons and was considered a rare disorder of men of northern European ancestry (6). The diagnosis was usually made in patients with end-stage disease, who had bronze diabetes and cirrhosis. However, recent screening studies have found that iron overload from hemochromatosis is far more common than previously thought. The estimated prevalence in the United States is 2 to 8 cases per 1,000 persons, making it the most com- mon genetic disease among whites (7–11). Iron removal by phlebotomy improves survival and morbidity (12,13) and, when started before the development of cirrhosis or diabetes, may lead to a normal life expectancy (14). These findings have led to recommendations for increased case detection and universal screening using phenotypic test- ing (eg, transferrin saturation) to permit early treatment before the onset of clinical disease (3). Despite these recommendations, several factors have caused hemochromatosis to remain underdiagnosed and underreported (4,15). What were believed to be the usual clinical manifestations, such as skin pigmentation, diabe- tes mellitus, and cirrhosis or liver disease, actually are infrequent among patients with hemochromatosis (4). In addition, the symptoms of hemochromatosis are easily confused with those of such common diseases as alcohol- ism, arthritis, or impotence. For example, among a large case series, 44% to 75% of patients had signs and symp- toms compatible with hemochromatosis, yet the disease was unrecognized for many years before diagnosis (16,17). Failure to detect hemochromatosis increases the likelihood that irreversible adverse health effects will oc- cur and increases the future financial burden associated with health care for persons with hemochromatosis. To date, only anecdotal information has been available about patients’ experiences before, during, and after the diagnosis of hemochromatosis. As screening and early detection have been increasingly recommended, clini- cians must address the potential harm associated with early diagnosis in patients who are asymptomatic and whose disease may never become clinically manifest (18). From the Centers for Disease Control and Prevention (SMM, SAJ, RY), National Center for Chronic Disease Prevention and Health Promo- tion, Division of Nutrition and Physical Activity, Atlanta, Georgia; School of Biology (BLP), Georgia Institute of Technology, Atlanta, Georgia; Southern Iron Overload Disorders (JCB), Birmingham, Ala- bama; LDS Hospital (CQE), Department of Medicine, Salt Lake City, Utah; and the Department of Gastroenterology (PCA), University of Western Ontario, London Health Science Center, London, Ontario, Canada. Supported by the Centers for Disease Control and Prevention Project Number 1632. Requests for reprints should be addressed to Sharon McDonnell, MD, MPH, Centers for Disease Control and Prevention, Division of International Health, MS C-08, 4770 Buford Highway, Atlanta, Georgia 30341. Manuscript submitted September 28, 1998, and accepted in revised form February 16, 1999. 1999 by Excerpta Medica, Inc. 0002-9343/99/$–see front matter 619 All rights reserved. PII S0002-9343(99)00120-5