Iron Overload

Aetiology

  • Primary - long-term excess iron absorption with parenchymal overload (rather than macrophage iron loading)
    • Hereditary haemochromatosis - commonest form is due to mutations in HFE gene (95%)
      • Decreased synthesis of hepcidin and increased iron absorption results in gradual iron accumulation with risk of end-organ damage
  • Secondary
    • Transfusional - repeated red cell transfusions
    • Massive ineffective erythropoiesis - thalassaemia, sideroblastic anaemias
    • Refractory hypoplastic anaemias - red cell aplasia, myelodysplasia (MDS)

Clinical presentation

Clinical features of hereditary haemochromatosis

  • Presentation usually in middle age or later
  • Iron overload > 5g
  • Weakness/fatigue
  • Joint pains
  • Impotence
  • Arthritis
  • Cirrhosis
  • Diabetes
  • Cardiomyopathy

Investigations

Diagnosis of hereditary haemochromatosis

  • Genetic testing - patients are usually C282Y homozygotes (HFE gene mutation), occasionally C282Y/H63DD, mutations of other iron regulatory proteins also tested for (but very rare)
  • Bloods - transferrin saturation >50%, serum ferritin >300 µg/l in men or >200 µg/l in pre-menopausal women
  • Liver biopsy - rarely needed, non-invasive techniques such as fibroscan avaliable to assess for cirrhosis
  • + family screening

Management

Hereditary haemochromatosis

  • Weekly venesection

Secondary iron overload

  • Iron chelating ages - desferrioxamine, deferiprone, deferasirox