Build-up of too much iron

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 features of hereditary haemochromatosis

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

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