Excess total body iron leading to deposition in specific organs, particularly the liver.

  • Can be
    • Primary
      • Most commonly Hereditary Haemochromatosis (see below)
      • Other causes include congenital acaeruloplasminaemia and congenital atransferrinaemia
    • Secondary
      • Parenteral iron-overload (e.g. repeated blood transfusions)
      • Iron-loading anaemia (e.g. thalassaemia, sideroblastic anaemia, pyruvate kinase deficiency)
      • Liver disease
      • NB In secondary disease, the history/examination will usually point towards the diagnosis.  The patient, however, can present similarly to HHC.
        • They can be managed by iron chelating drugs e.g. Desferrioxamine, deferiprone and deferasirox
    • Complex
      • Juvenile haemochromatosis
      • Neonatal haemochromatosis
      • Alcoholic liver disease
      • Porphyria cutanea tarda

Hereditary Haemochromatosis

  • In HHC, iron is deposited throughout the body and total iron stores can reach 20-60g (normally 4g).
    • Due to increased intestinal absorption
      • Homozygous (autosomal recessive) condition, most commonly due to a point mutation (C282Y) in the HFE protein, which is normally though to interact with the transferrin receptor in the basolateral membrane of intestinal enterocytes
        • Other mutations can also cause HHC e.g. H63D
      • Note that this mutation is present in around 0.4% of the population but <50% of these people have HHC
        • Other factors are inevitable
  • Most commonly/seriously affects the liver, first periportally and then further out.
    • Leads to the development of fibrous tissue and formation of a nodular cirrhosis


  • Patients usually present in middle age (30-50)
  • Initial symptoms are often vague (and may not be present)
    • e.g. fatigue, weakness, varus joint arthropathy, non-specific abdominal pain; impotence, loss of libido
    • features of liver disease may be present, as can features of diabetes (deposition in pancreatic cells) and heart failure.
    • Lead-grey skin pigmentation due to excess melanin in exposed areas, axillae, groins and genitalia.
    • Other features may include testicular atrophy
    • Pseudogout


  • Assess iron stores
    • Ferritin >1000μg/l is suggestive of haemochromatosis
      • If <1000, consider inflammatory disease or excess alcohol
    • Transferrin saturation >45% suggests overload
  • LFTs (as well as FBC, U&Es and maybe serum antibodies/serology)
    • U
  • MRI may show iron deposition in the liver (but has poor sensitivity)
  • Liver Biopsy
    • Hepatic iron index (μmol iron/g liver/age) >1.9 suggests hereditary haemochromatosis (or other primary disease)
  • Genetic testing
    • C282Y and H63D are both testable


  • Weekly venesection of 500ml of blood (250mg iron) until serum iron normalises (ferritin <50μg/l)
    • Can take 2 years or more
    • Although liver and cardiac function usually improves, symptoms of diabetes and joint pain can persist (diabetes is often permanent)
  • Transplant is an option for patients with fulminant liver failure
  • First degree relatives should be genetically tested and have LFTs/serum ferritin
    • If LFTs are abnormal, liver biopsy is indicated as cirrhosis may be present
    • If serum ferritin is high, venesection should be considered
  • Hepatocellular carcinoma screening should be offered routinely

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: