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Hemochromatosis

Last updated: October 14, 2020

Summary

Hemochromatosis is a condition that leads to abnormal iron deposition in specific organs. There are two main types: primary (hereditary) and secondary (e.g., transfusion-related). The most common form is hereditary autosomal recessive hemochromatosis type 1, which is caused by an underlying genetic defect that results in partially uninhibited absorption of iron in the small intestine. Hemochromatosis is mostly asymptomatic but can become symptomatic, usually between the third and fifth decade of life, when poisonous levels of iron have had time to accumulate in the body. Symptoms include fatigue, hyperpigmentation, diabetes mellitus ("bronze diabetes"), and arthralgia. The deposits may lead to various organ diseases, the most typical being the development of liver cirrhosis, which is accompanied by an increased risk of hepatocellular carcinoma (HCC). Serum ferritin and transferrin saturation levels are typically elevated. Molecular genetic testing or a liver biopsy may be used to confirm the diagnosis. Treatment primarily consists of repeated phlebotomy to reduce iron levels. In addition, dietary changes and drug therapy (chelating agents such as deferoxamine) may be used to influence the amount of iron in the body.

Epidemiology

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

References:[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

Primary (hereditary) hemochromatosis

  • Classical and most frequent form: adult hemochromatosis type I
  • Further forms: Hemochromatosis types II–IV are also hereditary, but significantly less frequent.

HLA A3 as in HA3mochromatosis!

Secondary hemochromatosis

References:[2][4]

Pathophysiology

Hemochromatosis type I

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

References:[5][6]

Clinical features

In combination with diabetes mellitus, bronze-colored skin pigmentation is also referred to as "bronze diabetes.”
References:[2][8][9][10]

Diagnostics

As a result of its subtle and primarily asymptomatic course, hemochromatosis is often an incidental diagnosis first detected during routine checks or diagnosed only once signs of advanced organ involvement become apparent.

Laboratory tests

Genetic tests

Imaging

Liver biopsy

References:[11][12][13][14]

Treatment

Primary hemochromatosis

  • Dietary changes
    • Diet low in iron
    • Restriction of alcohol and vitamin C supplements
    • Consumption of tea
  • Therapeutic phlebotomy (first-line treatment)
    • Initially 1–2 phlebotomy sessions per week; after reaching target ferritin and hemoglobin levels, phlebotomy should be performed every 2–4 months.
    • Target levels: serum ferritin 20–50 μg/L; hemoglobin > 12 g/dL (or 120 g/L)
    • Prognosis: initiation of therapy in the pre-cirrhotic phase → normal life expectancy and no organ damage
  • Drug-induced iron chelation
    • Agents: deferoxamine, deferasirox, or deferiprone
    • Indication: particularly when phlebotomy is contraindicated, e.g., in cases of anemia, severe heart disease, or difficult venipuncture

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

Secondary hemochromatosis

References:[14][15][16][17]

References

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  2. Recognition and Management of Hereditary Hemochromatosis. http://www.aafp.org/afp/2002/0301/p853.html. 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. https://www.uptodate.com/contents/genetics-of-hereditary-hemochromatosis.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. 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
  8. Hemochromatosis and sexual dysfunction. http://www.nature.com/ijir/journal/v15/n6/full/3901019a.html. Updated: March 31, 2003. Accessed: April 4, 2017.
  9. Schrier SL, Bacon BR. Clinical manifestations and diagnosis of hereditary hemochromatosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemochromatosis?source=search_result&search=secondary%20hemochromatosis&selectedTitle=2~150#H7.Last updated: December 9, 2016. Accessed: April 4, 2017.
  10. Kew MC. Hepatic iron overload and hepatocellular carcinoma. Liver Cancer. 2014; 3 (1): p.31-40. doi: 10.1159/000343856 . | Open in Read by QxMD
  11. Goljan EF. Rapid Review Pathology. Elsevier Saunders ; 2013
  12. Screening for hemochromatosis. http://www.sciencedirect.com/science/article/pii/S0009898101007112. Updated: January 1, 2002. Accessed: April 4, 2017.
  13. Schrier SL, Bacon BR. Screening for hereditary hemochromatosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/screening-for-hereditary-hemochromatosis?source=see_link.Last updated: December 20, 2016. Accessed: April 4, 2017.
  14. 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
  15. Schrier SL, Bacon BR. Management of patients with hereditary hemochromatosis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-patients-with-hereditary-hemochromatosis?source=see_link#H13.Last updated: February 8, 2017. Accessed: April 4, 2017.
  16. Assi TB, Baz E. Current applications of therapeutic phlebotomy. Blood Transfus. 2014; 12 (Suppl 1): p.s75–s83. doi: 10.2450/2013.0299-12 . | Open in Read by QxMD
  17. Gattermann N. The treatment of secondary hemochromatosis. Dtsch Arztebl Int. 2009; 106 (30): p.499-504. doi: 10.3238/arztebl.2009.0499 . | Open in Read by QxMD
  18. Herold G. Internal Medicine. Herold G ; 2014
  19. Hemochromatosis. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hemochromatosis/. Updated: July 1, 2014. Accessed: April 4, 2017.
  20. Sickle cell disease and hemochromatosis. https://www.ncbi.nlm.nih.gov/pubmed/1951309. Updated: October 1, 1991. Accessed: April 4, 2017.
  21. Schrier SL, Bacon BR. Patient education: Hemochromatosis (hereditary iron overload) (Beyond the Basics). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/hemochromatosis-hereditary-iron-overload-beyond-the-basics.Last updated: March 13, 2017. Accessed: April 4, 2017.
  22. Successful treatment of erectile dysfunction and infertility by venesection in a patient with primary haemochromatosis. https://www.ncbi.nlm.nih.gov/pubmed/11507369. Updated: August 1, 2001. Accessed: April 4, 2017.
  23. Duchini A. Hemochromatosis Workup. Hemochromatosis Workup. New York, NY: WebMD. http://emedicine.medscape.com/article/177216-workup#c8. Updated: April 4, 2017. Accessed: April 4, 2017.
  24. Aronow WS. Management of cardiac hemochromatosis. Arch Med Sci. 2017; 14 (3): p.560-568. doi: 10.5114/aoms.2017.68729 . | Open in Read by QxMD