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Genetics Home Reference: your guide to understanding genetic conditions
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Hemochromatosis

Reviewed October 2006

What is hemochromatosis?

Hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hemochromatosis is also called an iron overload disorder.

Early symptoms of hemochromatosis are nonspecific and may include fatigue, joint pain, abdominal pain, and loss of sex drive. Later signs and symptoms can include arthritis, liver disease, diabetes, heart abnormalities, and skin discoloration. The appearance and progression of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.

Hemochromatosis is classified by type depending on the age of onset and other factors such as genetic cause and mode of inheritance. Hemochromatosis type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) are adult-onset disorders. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause.

Type 2 hemochromatosis is a juvenile-onset disorder. Iron accumulation begins early in life, and symptoms may begin to appear in childhood. By age 20, decreased or absent secretion of sex hormones is evident. Females usually begin menstruation in a normal manner, but menses stop after a few years. Males may experience delayed puberty or sex hormone deficiency symptoms such as impotence. If the disorder is untreated, heart disease is evident by age 30. Onset of type 3 hemochromatosis is usually intermediate between types 1 and 2. Symptoms of type 3 hemochromatosis generally begin before age 30.

In rare cases, iron overload begins before birth. These cases are called neonatal hemochromatosis. This type of hemochromatosis progresses rapidly and is characterized by liver damage that is apparent at birth or in the first day of life.

How common is hemochromatosis?

Type 1 hemochromatosis is one of the most common genetic disorders in the United States, affecting about 1 million people. It most often affects people of Northern European descent. The other types of hemochromatosis are considered rare and have been studied in only a small number of families worldwide.

What genes are related to hemochromatosis?

Mutations in the HAMP, HFE, HFE2, SLC40A1, and TFR2 genes cause hemochromatosis.

The HAMP, HFE, HFE2, SLC40A1, and TFR2 genes play an important role in regulating the absorption, transport, and storage of iron. Mutations in these genes impair the control of iron absorption during digestion and alter the distribution of iron to other parts of the body. As a result, iron accumulates in tissues and organs, which can disrupt their normal functions.

Each type of hemochromatosis is caused by mutations in a specific gene. Type 1 hemochromatosis is caused by mutations in the HFE gene, and type 2 hemochromatosis is caused by mutations in either the HFE2 or HAMP gene. Mutations in the TFR2 gene cause type 3 hemochromatosis, and mutations in the SLC40A1 gene cause type 4 hemochromatosis. The cause of neonatal hemochromatosis is unknown.

Related Gene(s)

Changes in these genes are associated with hemochromatosis.

  • HAMP
  • HFE
  • HFE2
  • SLC40A1
  • TFR2

How do people inherit hemochromatosis?

Hemochromatosis types 1, 2, and 3 are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.

Type 4 hemochromatosis is distinguished by its autosomal dominant inheritance pattern. With this type of inheritance, one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition.

The inheritance pattern of neonatal hemochromatosis is unknown.

Where can I find information about diagnosis or management of hemochromatosis?

These resources address the diagnosis or management of hemochromatosis and may include treatment providers.

  • GeneFacts: Hereditary Hemochromatosis: Diagnosis (http://genefacts.org/index.php?option=com_content&view=article&id=159%3Ahereditary-hemochromatosis&catid=81%3Acondition-specific&Itemid=458&limitstart=2)
  • GeneFacts: Hereditary Hemochromatosis: Management (http://genefacts.org/index.php?option=com_content&view=article&id=159%3Ahereditary-hemochromatosis&catid=81%3Acondition-specific&Itemid=458&limitstart=3)
  • Gene Review: HFE-Associated Hereditary Hemochromatosis (http://www.ncbi.nlm.nih.gov/books/NBK1440)
  • Gene Review: Juvenile Hereditary Hemochromatosis (http://www.ncbi.nlm.nih.gov/books/NBK1170)
  • Gene Review: TFR2-Related Hereditary Hemochromatosis (http://www.ncbi.nlm.nih.gov/books/NBK1349)
  • Genetic Testing Registry: Hemochromatosis type 2A (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1865614)
  • Genetic Testing Registry: Hemochromatosis type 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858664)
  • Genetic Testing Registry: Hemochromatosis type 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1853733)
  • Genetic Testing Registry: Hereditary hemochromatosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0392514)
  • Genetic Testing Registry: Neonatal hemochromatosis (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268059)
  • MedlinePlus Encyclopedia: Hemochromatosis (http://www.nlm.nih.gov/medlineplus/ency/article/000327.htm)

You might also find information on the diagnosis or management of hemochromatosis in Educational resources (http://ghr.nlm.nih.gov/condition/hemochromatosis/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/hemochromatosis/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about hemochromatosis?

You may find the following resources about hemochromatosis helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for hemochromatosis?

  • Bronzed cirrhosis
  • Bronze Diabetes
  • Familial Hemochromatosis
  • genetic hemochromatosis
  • Haemochromatosis
  • HC
  • Hemochromatoses
  • HH
  • HLAH
  • Iron storage disorder
  • Pigmentary cirrhosis
  • Primary Hemochromatosis
  • Troisier-Hanot-Chauffard syndrome
  • Von Recklenhausen-Applebaum disease

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about hemochromatosis?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding hemochromatosis?

arthritis ; autosomal ; autosomal dominant ; autosomal recessive ; cell ; cirrhosis ; congenital ; deficiency ; diabetes ; digestion ; excretion ; familial ; gene ; giant cell ; hepatitis ; hereditary ; hormone ; impotence ; inheritance ; inheritance pattern ; inherited ; iron ; joint ; juvenile ; menopause ; menses ; menstruation ; metabolism ; mode of inheritance ; neonatal ; pancreas ; progression ; puberty ; recessive ; secretion ; sex hormone ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Alexander J, Kowdley KV. Hereditary hemochromatosis: genetics, pathogenesis, and clinical management. Ann Hepatol. 2005 Oct-Dec;4(4):240-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16432488?dopt=Abstract)
  • Anderson GJ, Powell LW. HFE and non-HFE hemochromatosis. Int J Hematol. 2002 Oct;76(3):203-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12416729?dopt=Abstract)
  • Beutler E. Hemochromatosis: genetics and pathophysiology. Annu Rev Med. 2006;57:331-47. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16409153?dopt=Abstract)
  • Camaschella C, Roetto A, Calì A, De Gobbi M, Garozzo G, Carella M, Majorano N, Totaro A, Gasparini P. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet. 2000 May;25(1):14-5. (http://www.ncbi.nlm.nih.gov/pubmed/10802645?dopt=Abstract)
  • Camaschella C, Roetto A, De Gobbi M. Juvenile hemochromatosis. Semin Hematol. 2002 Oct;39(4):242-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12382199?dopt=Abstract)
  • De Gobbi M, Roetto A, Piperno A, Mariani R, Alberti F, Papanikolaou G, Politou M, Lockitch G, Girelli D, Fargion S, Cox TM, Gasparini P, Cazzola M, Camaschella C. Natural history of juvenile haemochromatosis. Br J Haematol. 2002 Jun;117(4):973-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12060140?dopt=Abstract)
  • Dolbey CH. Hemochromatosis: a review. Clin J Oncol Nurs. 2001 Nov-Dec;5(6):257-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11899626?dopt=Abstract)
  • Heeney MM, Andrews NC. Iron homeostasis and inherited iron overload disorders: an overview. Hematol Oncol Clin North Am. 2004 Dec;18(6):1379-403, ix. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15511621?dopt=Abstract)
  • Kelly AL, Lunt PW, Rodrigues F, Berry PJ, Flynn DM, McKiernan PJ, Kelly DA, Mieli-Vergani G, Cox TM. Classification and genetic features of neonatal haemochromatosis: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism. J Med Genet. 2001 Sep;38(9):599-610. (http://www.ncbi.nlm.nih.gov/pubmed/11546828?dopt=Abstract)
  • Knisely AS, Mieli-Vergani G, Whitington PF. Neonatal hemochromatosis. Gastroenterol Clin North Am. 2003 Sep;32(3):877-89, vi-vii. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14562579?dopt=Abstract)
  • Le Gac G, Férec C. The molecular genetics of haemochromatosis. Eur J Hum Genet. 2005 Nov;13(11):1172-85. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16132052?dopt=Abstract)
  • Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, Cassanelli S, Trenor CC, Gasparini P, Andrews NC, Pietrangelo A. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J Clin Invest. 2001 Aug;108(4):619-23. (http://www.ncbi.nlm.nih.gov/pubmed/11518736?dopt=Abstract)
  • Njajou OT, Vaessen N, Joosse M, Berghuis B, van Dongen JW, Breuning MH, Snijders PJ, Rutten WP, Sandkuijl LA, Oostra BA, van Duijn CM, Heutink P. A mutation in SLC11A3 is associated with autosomal dominant hemochromatosis. Nat Genet. 2001 Jul;28(3):213-4. (http://www.ncbi.nlm.nih.gov/pubmed/11431687?dopt=Abstract)
  • Pietrangelo A. Hereditary hemochromatosis--a new look at an old disease. N Engl J Med. 2004 Jun 3;350(23):2383-97. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15175440?dopt=Abstract)
  • Pietrangelo A. Non-HFE hemochromatosis. Hepatology. 2004 Jan;39(1):21-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14752817?dopt=Abstract)
  • Pietrangelo A. Non-HFE hemochromatosis. Semin Liver Dis. 2005 Nov;25(4):450-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16315138?dopt=Abstract)
  • Pietrangelo A. The ferroportin disease. Blood Cells Mol Dis. 2004 Jan-Feb;32(1):131-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14757427?dopt=Abstract)
  • Wheeler CJ, Kowdley KV. Hereditary hemochromatosis: a review of the genetics, mechanism, diagnosis, and treatment of iron overload. Compr Ther. 2006 Spring;32(1):10-6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16785576?dopt=Abstract)
  • Whitington PF. Fetal and infantile hemochromatosis. Hepatology. 2006 Apr;43(4):654-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16557536?dopt=Abstract)
  • Yen AW, Fancher TL, Bowlus CL. Revisiting hereditary hemochromatosis: current concepts and progress. Am J Med. 2006 May;119(5):391-9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16651049?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2006
Published: March 2, 2015