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Hereditary haemochromatosis (HH)

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Hereditary haemochromatosis (HH) is a multiorgan disease in which iron regulation is disrupted, resulting in the toxic accumulation of iron in vital organs leading to life threatening complications such as cirrhosis, diabetes and heart disease (1).

  • the normal body content of iron is 2-6 g. Patients with haemochromatosis may have 50-60 g.

It is thought to be inherited in an autosomal recessive manner in people of northern European ancestry (1)

  • is the most common genetic predisposition disorder found in Caucasians, and one of the most common amongst people in Northern Europe
  • type 1 HH is caused by the following mutations to the HFE gene: C282Y homozygosity, H63D homozygosity and C282Y/H63D compound heterozygosity
    • this form of haemochromatosis is the most frequent and well-defined inherited cause of iron overload. It has been associated with a range of symptoms and clinical outcomes, including extreme tiredness, joint pain, diabetes, and liver disease (3,4)
  • atypical forms (a fifth of cases) have been described outside the northern European stereotype (2)

Mutations in the HFE gene on chromosome 6 (HFE-HH) and non-HFE mutations (non HFE-HH) predisposes an individual to increased, inappropriate absorption of dietary iron resulting in iron overload and organ damage (1)

  • HFE gene is responsible for the regulation of the primary iron regulatory hormone, hepcidin.
    • excess iron in body causes hepatocytes to secrete hepcidin which in turn decreases intestinal iron absorption by enterocytes and decreases iron release by macrophages
    • mutation of the HFE genes causes decreased hepcidin expression in response to elevated iron levels resulting in unregulated control of iron levels (1).

Approaches to treatment

  • while international guidelines differ slightly in their approaches to treatment, the premise of treatment is consistent;
    • to counteract iron overload,
    • prevent iron deposition in tissue,
    • and prevent organ dysfunction (3,4)
  • British Society of Haematology Committee Guidelines state that the primary treatment, phlebotomy (venesection) should be initiated in all fit patients with iron overload(4)
    • biochemical response is determined by assessing biochemical iron indices, transferrin saturation and ferritin concentration
    • clinically, the response to treatment will not be uniform amongst all individuals -this is dictated by the degree of progression of type 1 HH amongst individuals, and the nature of symptoms within individuals; some alleviated by phlebotomy, others not
    • active treatment of phlebotomy is followed by maintenance treatment, in the form of regular monitoring and phlebotomy as needed (4)
      • adverse events from phlebotomy include anaemia, fatigue, fainting, hematomas, and injection site pain
      • in cases where phlebotomy is contraindicated, or not tolerated, alternative treatment strategies including iron chelation (removal of excess iron from the body with medications) and erythrocytapheresis (selective withdrawal of red blood cells) amongst others have been considered
      • depending upon genotype, and degree of iron overload, specialist evaluation for liver pathology, including fibrosis assessment and cirrhosis, may also be recommended (1,2,3,4)


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