Clinical Review

Diagnosis and management of hereditary haemochromatosis

BMJ 2011; 342 doi: (Published 19 January 2011) Cite this as: BMJ 2011;342:c7251
  1. M A van Bokhoven, general practitioner and assistant professor in general practice1,
  2. C Th B M van Deursen, consultant internal medicine2,
  3. D W Swinkels, professor of clinical chemistry3
  1. 1Maastricht University, School for Public Health and Primary Care (CAPHRI), Department of General Practice, 6200 MD Maastricht, Netherlands
  2. 2Department of Internal Medicine and Gastroenterology, Atrium Medisch Centrum Parkstad, 6401 CX Heerlen, Netherlands
  3. 3Department of Laboratory Medicine, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, Netherlands
  1. Correspondence to: M A van Bokhoven loes.vanbokhoven{at}
  • Accepted 6 December 2010

Summary points

  • Hereditary haemochromatosis is an autosomal recessive disorder with a genetic prevalence of 0.4% in northern Europeans but a much lower clinical penetrance

  • Those affected are at increased risk of cirrhosis of the liver and hepatocellular carcinoma

  • Symptoms are often non-specific at presentation and include fatigue and arthropathy

  • If transferrin saturation and serum ferritin are raised, test for C282Y mutation of the HFE gene

  • First degree relatives of patients with clinically overt haemochromatosis can be screened for C282Y and H63D polymorphisms

  • Regular phlebotomy is the main treatment, although newly developed therapeutic approaches show promise

Hereditary haemochromatosis is an autosomal recessive genetic disease in which increased intestinal absorption of iron causes accumulation in tissues, primarily the liver, sometimes leading to organ damage. Liver deposits may result in cirrhosis and even death. A systematic review has shown that about 0.4% of people of northern European descent have the genetic mutation that increases the risk of developing haemochromatosis,1 but the clinical penetrance of the mutation is much lower than the genetic prevalence. Symptoms and signs are initially non-specific, so the disease is often diagnosed at a late stage when substantial organ damage has already occurred. The challenge is to avoid both overdiagnosis and underdiagnosis. Since the discovery of the genetic mutation, new knowledge has come to light on the pathophysiology and course of the disease. This has led to new recommendations on diagnosis and treatment. In addition, new treatments are under evaluation. We review evidence from experimental and observational studies, systematic reviews, and guidelines to summarise for the general reader the clinical presentation, diagnosis, including early screening options, and management of hereditary haemochromatosis.

Sources and selection criteria

Initially, we made an extensive search of Medline, Embase, and the Cochrane Library for papers published until December 2009 using both MESH headings and free text related to hereditary haemochromatosis. …

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