Last updated: June 14, 2023

Summarytoggle arrow icon

Hemochromatosis refers to a group of conditions characterized by excess iron deposition (or increased risk of excess deposition) in the body as a result of increased iron absorption. Increased iron absorption leads to iron overload as there is no physiologic method for iron excretion (except through menstrual bleeding). Primary iron overload (primary/hereditary hemochromatosis) is caused by mutations in genes involved in regulating gastrointestinal iron absorption, resulting in iron over-absorption. Secondary iron overload (sometimes referred to as secondary hemochromatosis) is caused by conditions affecting iron metabolism (e.g., chronic liver disease) or excessive iron ingestion or infusion (e.g., from repeated transfusions to treat beta-thalassemia major). Patients with primary iron overload often only become symptomatic after irreversible damage has occurred, commonly in the third to fifth decades of life. Early clinical features are often nonspecific (e.g., fatigue, decreased libido, hyperpigmentation, symptoms of diabetes mellitus, arthralgia). Laboratory findings of elevated serum ferritin combined with elevated transferrin saturation are highly suggestive of iron overload. Genetic testing, MRI abdomen, and, occasionally, liver biopsy may be used to confirm the diagnosis. Treatment with therapeutic phlebotomy or chelating agents (e.g., deferoxamine) can prevent or mitigate the downstream effects of parenchymal iron deposition (e.g., cardiomyopathy, arrhythmia). The liver is the most commonly affected organ, and the development of cirrhosis is associated with an increased risk of hepatocellular carcinoma. Patients with iron overload should be advised to avoid alcohol consumption and vitamin C supplementation, as they increase iron absorption, which may lead to disease progression.

Epidemiologytoggle arrow icon

  • Prevalence: the most frequent genetic disease in the white population
  • Age of onset: individuals > 40 years


Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Primary (hereditary) hemochromatosis

HLA A3 as in HA3mochromatosis!

Secondary iron overload (secondary hemochromatosis)


Pathophysiologytoggle arrow icon

Hemochromatosis type I

In hereditary hemochromatosis, decreased hepcidin leads to iron overload. In secondary hemochromatosis, iron overload leads to increased hepcidin immediately after a blood transfusion (unless liver fibrosis or cirrhosis, which leads to decreased hepcidin synthesis, is present).


Clinical featurestoggle arrow icon

Hemochromatosis is asymptomatic in 75% of cases. [2]

General symptoms

  • Fatigue, lethargy
  • Increased susceptibility to infections [7]

Organ-specific symptoms

In combination with diabetes mellitus, bronze-colored skin pigmentation is also referred to as "bronze diabetes.”

Diagnosticstoggle arrow icon

General principles [10]

Laboratory studies [10]

Elevated serum ferritin in conjunction with elevated transferrin saturation is highly suggestive of iron overload. The combination of normal serum ferritin and transferrin saturation has a 97% negative predictive value. [10]

Imaging [10]

Liver biopsy [10]

The use of liver biopsy in hemochromatosis is limited, as the concentration and distribution pattern of hepatic iron can be assessed using noninvasive MRI. [13]

Treatmenttoggle arrow icon

Approach [10]

Management is guided by a specialist (e.g., hepatologist, gastroenterologist, or hematologist).

Therapeutic phlebotomy [10][12]

Iron chelation therapy [10]

Check renal function prior to administration of chelating agents because of the risk of nephrotoxicity and renal accumulation.

Drugs that delete iron (Fe) in hemochromatosis: deFeroxamine, deFerasirox, deFeriprone

Liver transplantation [10]

Additional therapies [10]

In patients with iron overload, alcohol use significantly increases the risk of progression of both liver fibrosis and cirrhosis.

Patient counseling [10]

Referencestoggle arrow icon

  1. Epidemiology and diagnostic testing for hemochromatosis and iron overload. Updated: May 14, 2015. Accessed: April 4, 2017.
  2. Recognition and Management of Hereditary Hemochromatosis. Updated: March 1, 2002. Accessed: April 4, 2017.
  3. McLaren GD, Gordeuk VR. Hereditary hemochromatosis: insights from the Hemochromatosis and Iron Overload Screening (HEIRS) Study. Hematology Am Soc Hematol Educ Program. 2009; 2009 (1): p.195-206.doi: 10.1182/asheducation-2009.1.195 . | Open in Read by QxMD
  4. Schrier SL, Bacon BR, Mentzer WC, Raby BA, Tirnauer JS. Genetics of Hereditary Hemochromatosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. Last updated: July 20, 2017. Accessed: July 16, 2018.
  5. Fleming RE, Britton RS, Waheed A, Sly WS, Bacon BR. Pathophysiology of hereditary hemochromatosis. Semin Liver Dis. 2005; 25 (4): p.411-419.doi: 10.1055/s-2005-923313 . | Open in Read by QxMD
  6. Vela D. Low hepcidin in liver fibrosis and cirrhosis; a tale of progressive disorder and a case for a new biochemical marker. Molecular Medicine. 2018; 24 (1).doi: 10.1186/s10020-018-0008-7 . | Open in Read by QxMD
  7. Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with infectious diseases: expanding spectrum. International Journal of Infectious Diseases. 2007; 11 (6): p.482-487.doi: 10.1016/j.ijid.2007.04.007 . | Open in Read by QxMD
  8. Kowdley KV. Iron, hemochromatosis, and hepatocellular carcinoma. Gastroenterology. 2004; 127 (5): p.S79-S86.doi: 10.1016/j.gastro.2004.09.019 . | Open in Read by QxMD
  9. Hemochromatosis and sexual dysfunction. Updated: March 31, 2003. Accessed: April 4, 2017.
  10. Kowdley KV, Brown KE, Ahn J, Sundaram V. ACG Clinical Guideline: Hereditary Hemochromatosis. Am J Gastroenterol. 2019; 114 (8): p.1202-1218.doi: 10.14309/ajg.0000000000000315 . | Open in Read by QxMD
  11. European Association For The Study Of The Liver. EASL clinical practice guidelines for HFE hemochromatosis. J Hepatol. 2010; 53 (1): p.3-22.doi: 10.1016/j.jhep.2010.03.001 . | Open in Read by QxMD
  12. Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS. Diagnosis and management of hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011; 54 (1): p.328-343.doi: 10.1002/hep.24330 . | Open in Read by QxMD
  13. Salomao MA. Pathology of Hepatic Iron Overload. Clin Liver Dis. 2021; 17 (4): p.232-237.doi: 10.1002/cld.1051 . | Open in Read by QxMD
  14. Caligiuri M, Levi MM, Kaushansky K, et al. Williams Hematology, 9E. McGraw-Hill Education / Medical ; 2015
  15. Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT). Updated: January 1, 2017. Accessed: November 5, 2020.
  16. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). Updated: January 1, 2014. Accessed: November 5, 2020.
  17. Rombout-Sestrienkova E, van Kraaij MGJ, Koek GH. How we manage patients with hereditary haemochromatosis. Br J Haematol. 2016; 175 (5): p.759-770.doi: 10.1111/bjh.14376 . | Open in Read by QxMD

Icon of a lock3 free articles remaining

You have 3 free member-only articles left this month. Sign up and get unlimited access.
 Evidence-based content, created and peer-reviewed by physicians. Read the disclaimer