Hemochromatosis - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Hemochromatosis is a genetic disorder causing a buildup of iron levels in the body over time. Common presenting features include fatigue and arthralgias.
Elevated transferrin saturation is the phenotypic hallmark of the disorder, and diagnosis is confirmed by genetic testing.
The main goal of treatment is to deplete elevated body iron stores and subsequently prevent its reaccumulation.
Complications may include cirrhosis, hepatocellular cancer, arthropathy, diabetes, and heart disease.

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Definition

Epidemiology

Etiology

Pathophysiology

Citations

Key Articles

Haute Autorité de Santé (France). Management of patients with HFE-related haemochromatosis (type 1 haemochromatosis). Jul 2005 [internet publication].[Full Text]
Kowdley KV, Brown KE, Ahn J, et al. ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol. 2019 Aug;114(8):1202-18.[Abstract][Full Text]
European Association for the Study of the Liver. EASL clinical practice guidelines on haemochromatosis. J Hepatol. 2022 Aug;77(2):479-502.[Abstract][Full Text]
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 Jul;54(1):328-43.[Abstract][Full Text]
Fitzsimons EJ, Cullis JO, Thomas DW, et al. Diagnosis and therapy of genetic haemochromatosis (review and 2017 update). Br J Haematol. 2018 May;181(3):293-303.[Abstract][Full Text]

Referenced Articles

1. McCune CA, Ravine D, Carter K, et al. Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients. Gut. 2006 Apr;55(4):554-62.[Abstract]
2. 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 Sep 2;341(10):718-24.[Abstract]
3. 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 Aug 1;145(3):209-23.[Abstract]
4. Kowdley KV, Brown KE, Ahn J, et al. Correction: ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol. 2019 Dec;114(12):1927.
5. Girelli D, Busti F, Brissot P, et al. Hemochromatosis classification: update and recommendations by the BIOIRON Society. Blood. 2022 May 19;139(20):3018-29.[Abstract][Full Text]
6. Haute Autorité de Santé (France). Management of patients with HFE-related haemochromatosis (type 1 haemochromatosis). Jul 2005 [internet publication].[Full Text]
7. Kowdley KV, Brown KE, Ahn J, et al. ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol. 2019 Aug;114(8):1202-18.[Abstract][Full Text]
8. European Association for the Study of the Liver. EASL clinical practice guidelines on haemochromatosis. J Hepatol. 2022 Aug;77(2):479-502.[Abstract][Full Text]
9. Olynyk JK, Ramm GA. Hemochromatosis. N Engl J Med. 2022 Dec 8;387(23):2159-70.[Abstract]
10. Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet. 2016 Aug 13;388(10045):706-16.[Abstract]
11. Adams PC, Reboussin DM, Barton JC, et al. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med. 2005 Apr 28;352(17):1769-78.[Abstract][Full Text]
12. Anderson GJ, Bardou-Jacquet E. Revisiting hemochromatosis: genetic vs. phenotypic manifestations. Ann Transl Med. 2021 Apr;9(8):731.[Abstract][Full Text]
13. Allen KJ, Gurrin LC, Constantine CC, et al. Iron-overload-related disease in HFE hereditary hemochromatosis. N Engl J Med. 2008 Jan 17;358(3):221-30.[Abstract][Full Text]
14. Hagström H, Ndegwa N, Jalmeus M, et al. Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers. Liver Int. 2021 Mar;41(3):545-53.[Abstract][Full Text]
15. National Institutes of Health. HFE homeostatic iron regulator [homo sapiens (human)]. Dec 2023 [internet publication].[Full Text]
16. Feder JN, Gnirke A, Thomas W, et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996 Aug;13(4):399-408.[Abstract]
17. Gurrin LC, Bertalli NA, Dalton GW, et al. HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity. Hepatology. 2009 Jul;50(1):94-101.[Abstract][Full Text]
18. Beutler E, Felitti VJ, Koziol JA, et al. Penetrance of 845G--> A (C282Y) HFE hereditary haemochromatosis mutation in the USA. Lancet. 2002 Jan 19;359(9302):211-8.[Abstract]
19. Guyader D, Jacquelinet C, Moirand R, et al. Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. Gastroenterology. 1998 Oct;115(4):929-36.[Abstract]
20. Beaton M, Guyader D, Deugnier Y, et al. Noninvasive prediction of cirrhosis in C282Y-linked hemochromatosis. Hepatology. 2002 Sep;36(3):673-8.[Abstract]
21. Allen KJ, Bertalli NA, Osborne NJ, et al; HealthIron Study Investigators. HFE Cys282Tyr homozygotes with serum ferritin concentrations below 1000 microg/L are at low risk of hemochromatosis. Hepatology. 2010 Sep;52(3):925-33.[Abstract][Full Text]
22. Rossi E, Bulsara MK, Olynyk JK, et al. Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population. Clin Chem. 2001 Feb;47(2):202-8.[Abstract][Full Text]
23. Bridle KR, Frazer DM, Wilkins SJ, et al. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet. 2003 Feb 22;361(9358):669-73.[Abstract]
24. Falize L, Guillygomarc'h A, Perrin M, et al. Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases. Hepatology. 2006 Aug;44(2):472-7.[Abstract][Full Text]
25. Dymock IW, Hamilton EB, Laws JW, et al. Arthropathy of haemochromatosis: clinical and radiological analysis of 63 patients with iron overload. Ann Rheum Dis. 1970 Sep;29(5):469-76.[Abstract][Full Text]
26. Valenti L, Fracanzani AL, Rossi V, et al. The hand arthropathy of hereditary hemochromatosis is strongly associated with iron overload. J Rheumatol. 2008 Jan;35(1):153-8.[Abstract]
27. Harty LC, Lai D, Connor S, et al. Prevalence and progress of joint symptoms in hereditary hemochromatosis and symptomatic response to venesection. J Clin Rheumatol. 2011 Jun;17(4):220-2.[Abstract]
28. Adams PC, Reboussin DM, Press RD, et al. Biological variability of transferrin saturation and unsaturated iron-binding capacity. Am J Med. 2007 Nov;120(11):999.e1-7.[Abstract][Full Text]
29. Cullis JO, Fitzsimons EJ, Griffiths WJ, et al. Investigation and management of a raised serum ferritin. Br J Haematol. 2018 May;181(3):331-40.[Abstract][Full Text]
30. American College of Medical Genetics and Genomics. Five things physicians and patients should question. Choosing Wisely, an initiative of the ABIM Foundation. 2021 [internet publication].[Full Text]
31. Gandon Y, Olivié D, Guyader D, et al. Non-invasive assessment of hepatic iron stores by MRI. Lancet. 2004 Jan 31;363(9406):357-62.[Abstract]
32. Adams PC, Speechley M, Barton JC, et al. Probability of C282Y homozygosity decreases as liver transaminase activities increase in participants with hyperferritinemia in the hemochromatosis and iron overload screening study. Hepatology. 2012 Jun;55(6):1722-6.[Abstract][Full Text]
33. Beaton M, Adams PC. Assessment of silent liver fibrosis in hemochromatosis C282Y homozygotes with normal transaminase levels. Clin Gastroenterol Hepatol. 2008 Jun;6(6):713-4.[Abstract][Full Text]
34. Cherfane CE, Hollenbeck RD, Go J, et al. Hereditary hemochromatosis: missed diagnosis or misdiagnosis? Am J Med. 2013 Nov;126(11):1010-5.[Abstract]
35. Eschewege E, Saddi R, Wacjman H, et al. Haemoglobin AIc in patients on venesection therapy for haemochromatosis [in French]. Diabetes Metab. 1982 Jun;8(2):137-40.[Abstract]
36. Yen AW, Fancher TL, Bowlus CL. Revisiting hereditary hemochromatosis: current concepts and progress. Am J Med. 2006 May;119(5):391-9.[Abstract]
37. McDermott JH, Walsh CH. Hypogonadism in hereditary hemochromatosis. J Clin Endocrinol Metabol. 2005 Apr;90(4):2451-5.[Abstract][Full Text]
38. Valenti L, Varenna M, Fracanzani AL, et al. Association between iron overload and osteoporosis in patients with hereditary hemochromatosis. Osteoporos Int. 2009 Apr;20(4):549-55.[Abstract]
39. Mehrany K, Drage LA, Brandhagen DJ, et al. Association of porphyria cutanea tarda with hereditary hemochromatosis. J Am Acad Dermatol. 2004 Aug;51(2):205-11.[Abstract]
40. Corradini E, Pietrangelo A. Iron and steatohepatitis. J Gastroenterol Hepatol. 2012 Mar;27(suppl 2):42-6.[Abstract]
41. Moirand R, Mortaji AM, Loréal O, et al. A new syndrome of liver iron overload with normal transferrin saturation. Lancet. 1997 Jan 11;349(9045):95-7.[Abstract]
42. 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 Mar;79(3):309-13.[Abstract]
43. Andersen RV, Tybjaerg-Hansen A, Appleyard M, et al. Hemochromatosis mutations in the general population: iron overload progression rate. Blood. 2004 Apr 15;103(8):2914-9.[Abstract][Full Text]
44. 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 Jul;54(1):328-43.[Abstract][Full Text]
45. Fitzsimons EJ, Cullis JO, Thomas DW, et al. Diagnosis and therapy of genetic haemochromatosis (review and 2017 update). Br J Haematol. 2018 May;181(3):293-303.[Abstract][Full Text]
46. Porto G, Brissot P, Swinkels DW, et al; European Molecular Genetics Quality Network. EMQN best practice guidelines for the molecular genetic diagnosis of hereditary hemochromatosis (HH). Eur J Hum Genet. 2016 Apr;24(4):479-95.[Abstract][Full Text]
47. King C, Barton DE. Best practice guidelines for the molecular genetic diagnosis of type 1 (HFE-related) hereditary haemochromatosis. BMC Med Genet. 2006 Nov 29;7:81.[Abstract][Full Text]
48. Gurrin LC, Osborne NJ, Constantine CC, et al. The natural history of serum iron indices for HFE C282Y homozygosity associated with hereditary hemochromatosis. Gastroenterology. 2008 Dec;135(6):1945-52.[Abstract][Full Text]
49. McDonnell SM, Grindon AJ, Preston BL, et al. A survey of phlebotomy among persons with hemochromatosis. Transfusion. 1999 Jun;39(6):651-6.[Abstract]
50. Nelson NP, Weng MK, Hofmeister MG, et al. Prevention of hepatitis A virus infection in the United States: recommendations of the advisory committee on immunization practices, 2020. MMWR Recomm Rep. 2020 Jul 3;69(5):1-38.[Abstract][Full Text]
51. Weng MK, Doshani M, Khan MA, et al. Universal hepatitis B vaccination in adults aged 19-59 years: updated recommendations of the advisory committee on immunization practices - United States, 2022. MMWR Morb Mortal Wkly Rep. 2022 Apr 1;71(13):477-83.[Abstract][Full Text]
52. Moretti D, van Doorn GM, Swinkels DW, et al. Relevance of dietary iron intake and bioavailability in the management of HFE hemochromatosis: a systematic review. Am J Clin Nutr. 2013 Aug;98(2):468-79.[Abstract][Full Text]
53. Phatak P, Brissot P, Wurster M, et al. A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis. Hepatology. 2010 Nov;52(5):1671-9.[Abstract][Full Text]
54. Cançado R, Melo MR, de Moraes Bastos R, et al. Deferasirox in patients with iron overload secondary to hereditary hemochromatosis: results of a 1-yr phase 2 study. Eur J Haematol. 2015 Dec;95(6):545-50.[Abstract]
55. Brissot P, Pietrangelo A, Adams PC, et al. Haemochromatosis. Nat Rev Dis Primers. 2018 Apr 5;4:18016.[Abstract][Full Text]
56. Liu J, Sun B, Yin H, et al. Hepcidin: a promising therapeutic target for iron disorders: a systematic review. Medicine (Baltimore). 2016 Apr;95(14):e3150.[Abstract][Full Text]
57. Vyoral D, Jiri Petrak. Therapeutic potential of hepcidin - the master regulator of iron metabolism. Pharmacol Res. 2017 Jan;115:242-54.[Abstract]
58. Niederau C, Fischer R, Pürschel A, et al. Long-term survival in patients with hereditary hemochromatosis. Gastroenterology. 1996 Apr;110(4):1107-19.[Abstract]
59. van Bokhoven MA, van Deursen CT, Swinkels DW. Diagnosis and management of hereditary haemochromatosis. BMJ. 2011 Jan 19;342:c7251.[Abstract][Full Text]
60. Asberg A, Hveem K, Thorstensen K, et al. Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons. Scand J Gastroenterol. 2001 Oct;36(10):1108-15.[Abstract]
61. Ellervik C, Birgens H, Tybjaerg-Hansen A, et al. Hemochromatosis genotypes and risk of 31 disease endpoints: meta-analyses including 66,000 cases and 226,000 controls. Hepatology. 2007 Oct;46(4):1071-80.[Abstract][Full Text]
62. Pilling LC, Tamosauskaite J, Jones G, et al. Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank. BMJ. 2019 Jan 16;364:k5222.[Abstract][Full Text]
63. Osborne NJ, Gurrin LC, Allen KJ, et al. HFE C282Y homozygotes are at increased risk of breast and colorectal cancer. Hepatology. 2010 Apr;51(4):1311-8.[Abstract][Full Text]
64. Strohmeyer G, Niederau C, Stremmel W. Survival and causes of death in hemochromatosis. Observations in 163 patients. Ann N Y Acad Sci. 1988;526:245-57.[Abstract]
65. Bardou-Jacquet E, Morcet J, Manet G, et al. Decreased cardiovascular and extrahepatic cancer-related mortality in treated patients with mild HFE hemochromatosis. J Hepatol. 2015 Mar;62(3):682-9.[Abstract]
66. Lymberopoulos P, Prakash S, Shaikh A, et al. Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States. Liver Transpl. 2023 Jan 1;29(1):15-25.[Abstract][Full Text]
67. Kowdley KV. Iron, hemochromatosis, and hepatocellular carcinoma. Gastroenterology. 2004 Nov;127(5 suppl 1):S79-86.[Abstract]
68. Guggenbuhl P, Deugnier Y, Boisdet JF, et al. Bone mineral density in men with genetic hemochromatosis and HFE gene mutation. Osteoporosis Int. 2005 Dec;16(12):1809-14.[Abstract]
69. Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with infectious diseases: expanding spectrum. Int J Infect Dis. 2007 Nov;11(6):482-7.[Abstract][Full Text]
70. Adams PC. Implications of genotyping of spouses to limit investigation of children in genetic hemochromatosis. Clin Genet. 1998 Mar;53(3):176-8.[Abstract]