UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Screening for hereditary hemochromatosis

Authors
Stanley L Schrier, MD
Bruce R Bacon, MD
Section Editor
William C Mentzer, MD
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

Hereditary hemochromatosis (HH), also called genetic hemochromatosis, is an inherited disorder in which mutations in the HFE gene or other genes (eg, hemojuvelin, hepcidin, ferroportin, transferrin receptor-2) (table 1) cause a life-long increase in intestinal iron absorption, ultimately resulting in some patients in systemic iron overload and end-organ damage, especially in the liver, heart, and endocrine organs.

While HH in a symptomatic patient may be far advanced, screening of first-degree family members or normal populations may allow diagnosis at an early stage, before irreversible organ damage has occurred. While there is general agreement that first-degree relatives of patients with HH should be screened for the disease, population screening for HH remains a topic of debate [1-3]. The pros and cons of both of these approaches will be reviewed here.

The genetics, pathophysiology, clinical manifestations, diagnosis, and treatment of HH are discussed separately. (See "Genetics of hereditary hemochromatosis" and "Clinical manifestations and diagnosis of hereditary hemochromatosis" and "Approach to the patient with suspected iron overload" and "Management of patients with hereditary hemochromatosis".)

OVERVIEW OF DISEASE PREVENTION AND SCREENING FOR HH

Screening is an important component of preventive care. It consists of the identification of an asymptomatic disease, harmful condition, or risk factor, with the overall aim that the condition be caught early before it causes harm to the affected individual. Since hereditary hemochromatosis (HH) is present at birth, its cause cannot be removed, and primary prevention is not practical. However, secondary prevention, which aims to detect early disease when it is asymptomatic and when treatment might stop it from progressing, is a viable option. (See "Evidence-based approach to prevention", section on 'Preventive activities in clinical settings'.)

Disease penetrance — Disease penetrance is an important issue when family and population screening for HH are performed, as a significant percent of subjects found to have homozygous HH at the time of screening have no evidence for iron overload either at the time of screening [1,4] or after 12 or more years of follow-up [5-8].

                    

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Jun 01 00:00:00 GMT+00:00 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Beutler E, Felitti VJ, Koziol JA, et al. Penetrance of 845G--> A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet 2002; 359:211.
  2. McDonnell SM, Parrish RG. Hereditary hemochromatosis and its elusive natural history. Arch Intern Med 2003; 163:2421.
  3. Dubois S, Kowdley KV. The importance of screening for hemochromatosis. Arch Intern Med 2003; 163:2424.
  4. Bulaj ZJ, Ajioka RS, Phillips JD, et al. Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med 2000; 343:1529.
  5. Allen KJ, Gurrin LC, Constantine CC, et al. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med 2008; 358:221.
  6. Whitlock EP, Garlitz BA, Harris EL, et al. Screening for hereditary hemochromatosis: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2006; 145:209.
  7. Andersen RV, Tybjaerg-Hansen A, Appleyard M, et al. Hemochromatosis mutations in the general population: iron overload progression rate. Blood 2004; 103:2914.
  8. Olynyk JK, Hagan SE, Cullen DJ, et al. Evolution of untreated hereditary hemochromatosis in the Busselton population: a 17-year study. Mayo Clin Proc 2004; 79:309.
  9. Edwards CQ, Kushner JP. Screening for hemochromatosis. N Engl J Med 1993; 328:1616.
  10. Pippard MJ. Detection of iron overload. Lancet 1997; 349:73.
  11. Edwards CQ, Griffen LM, Goldgar D, et al. Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N Engl J Med 1988; 318:1355.
  12. Dadone MM, Kushner JP, Edwards CQ, et al. Hereditary hemochromatosis. Analysis of laboratory expression of the disease by genotype in 18 pedigrees. Am J Clin Pathol 1982; 78:196.
  13. Milman N. Iron status markers in hereditary haemochromatosis: distinction between individuals being homozygous and heterozygous for the haemochromatosis allele. Eur J Haematol 1991; 47:292.
  14. Adams PC, Reboussin DM, Press RD, et al. Biological variability of transferrin saturation and unsaturated iron-binding capacity. Am J Med 2007; 120:999.e1.
  15. Bacon BR, Adams PC, Kowdley KV, et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54:328.
  16. Beutler E, Felitti V, Gelbart T, Ho N. The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic. Ann Intern Med 2000; 133:329.
  17. Koziol JA, Felitti VJ, Beutler E. The effect of HFE genotypes on measurements of iron overload. Ann Intern Med 2002; 137:700.
  18. Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med 2005; 352:1769.
  19. Schmitt B, Golub RM, Green R. 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 2005; 143:522.
  20. Qaseem A, Aronson M, Fitterman N, et al. Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2005; 143:517.
  21. Alper JS, Geller LN, Barash CI, et al. Genetic discrimination and screening for hemochromatosis. J Public Health Policy 1994; 15:345.
  22. Jackson HA, Carter K, Darke C, et al. HFE mutations, iron deficiency and overload in 10,500 blood donors. Br J Haematol 2001; 114:474.
  23. Mainous AG 3rd, Gill JM, Pearson WS. Should we screen for hemochromatosis? An examination of evidence of downstream effects on morbidity and mortality. Arch Intern Med 2002; 162:1769.
  24. Delatycki MB, Allen KJ, Nisselle AE, et al. Use of community genetic screening to prevent HFE-associated hereditary haemochromatosis. Lancet 2005; 366:314.
  25. Shaheen NJ, Lawrence LB, Bacon BR, et al. Insurance, employment, and psychosocial consequences of a diagnosis of hereditary hemochromatosis in subjects without end organ damage. Am J Gastroenterol 2003; 98:1175.
  26. Power TE, Adams PC. Psychosocial impact of C282Y mutation testing for hemochromatosis. Genet Test 2001; 5:107.
  27. U.S. Preventive Services Task Force. Screening for hemochromatosis: recommendation statement. Ann Intern Med 2006; 145:204.
  28. Harrison HF, Harrison BW, Walker AP, et al. Screening for hemochromatosis and iron overload: satisfaction with results notification and understanding of mailed results in unaffected participants of the HEIRS study. Genet Test 2008; 12:491.
  29. Cartwright GE, Skolnick M, Amos DB, et al. Inheritance of hemochromatosis: linkage to HLA. Trans Assoc Am Physicians 1978; 91:273.
  30. Jacobs EM, Hendriks JC, van Deursen CT, et al. Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study. J Hepatol 2009; 50:174.
  31. El-Serag HB, Inadomi JM, Kowdley KV. Screening for hereditary hemochromatosis in siblings and children of affected patients. A cost-effectiveness analysis. Ann Intern Med 2000; 132:261.
  32. Tavill AS, American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association. Diagnosis and management of hemochromatosis. Hepatology 2001; 33:1321.
  33. Phatak PD, Bonkovsky HL, Kowdley KV. Hereditary hemochromatosis: time for targeted screening. Ann Intern Med 2008; 149:270.
  34. Pietrangelo A. Hereditary hemochromatosis--a new look at an old disease. N Engl J Med 2004; 350:2383.
  35. Niederau C, Niederau CM, Lange S, et al. Screening for hemochromatosis and iron deficiency in employees and primary care patients in Western Germany. Ann Intern Med 1998; 128:337.
  36. Olynyk JK, Cullen DJ, Aquilia S, et al. A population-based study of the clinical expression of the hemochromatosis gene. N Engl J Med 1999; 341:718.
  37. http://www.ncbi.nlm.nih.gov/sites/GeneTests/ (Accessed on July 11, 2011).
  38. Balan V, Baldus W, Fairbanks V, et al. Screening for hemochromatosis: a cost-effectiveness study based on 12,258 patients. Gastroenterology 1994; 107:453.
  39. Phatak PD, Sham RL, Raubertas RF, et al. Prevalence of hereditary hemochromatosis in 16031 primary care patients. Ann Intern Med 1998; 129:954.
  40. Baer DM, Simons JL, Staples RL, et al. Hemochromatosis screening in asymptomatic ambulatory men 30 years of age and older. Am J Med 1995; 98:464.
  41. Adams PC, Valberg LS. Screening blood donors for hereditary hemochromatosis: decision analysis model comparing genotyping to phenotyping. Am J Gastroenterol 1999; 94:1593.
  42. Waalen J, Felitti V, Gelbart T, et al. Prevalence of hemochromatosis-related symptoms among individuals with mutations in the HFE gene. Mayo Clin Proc 2002; 77:522.
  43. Adams PC, Passmore L, Chakrabarti S, et al. Liver diseases in the hemochromatosis and iron overload screening study. Clin Gastroenterol Hepatol 2006; 4:918.
  44. Powell LW, Dixon JL, Ramm GA, et al. Screening for hemochromatosis in asymptomatic subjects with or without a family history. Arch Intern Med 2006; 166:294.
  45. Burke W, Thomson E, Khoury MJ, et al. Hereditary hemochromatosis: gene discovery and its implications for population-based screening. JAMA 1998; 280:172.
  46. Bacon BR. Screening for hemochromatosis. Arch Intern Med 2006; 166:269.