Aetiology of iron overload

Causes of iron overload

Iron overload syndromes can be divided into three groups:

• Hereditary haemochromatosis
  
  
  • HFE-related
    • C282Y/C282Y
    • C282Y/H63D
    • other HFE mutations
      
      
  • non–HFE-related
    • hemojuvelin (HJV)
    • transferrin receptor-2 (TfR2)
    • ferroportin (SLC40A1)
    • hepcidin (HAMP)
    • African iron overload
      
      
• Secondary iron overload
  
  
  • iron-loading anaemias
    • thalassemia major
    • sideroblastic
    • chronic haemolytic anaemia
    • aplastic anaemia
    • pyruvate kinase deficiency
    • pyridoxine-responsive anaemia
      
      
  • parenteral iron overload
    • red blood cell transfusions e.g.
      • parenteral iron overload in blood transfusions:
      • thalassaemia major
      • sickle cell disease
      • myelodysplasia
        
        
    • iron–dextran injections
    • long-term haemodialysis
      
      
  • excess dietary iron:
    • Bantu haemochromatosis
      
      
  • chronic liver disease
    • porphyria cutanea tarda
    • hepatitis C
    • hepatitis B
    • alcoholic liver disease
    • non-alcoholic fatty liver disease
    • following portocaval shunt
      
      
  • dysmetabolic iron overload syndrome
    
    
• Miscellaneous
  • neonatal iron overload
  • aceruloplasminemia
  • congenital atransferrinemia

A high alcohol intake is associated with more rapid development of haemochromatosis.

Reference:

• (1) Bacon BR et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011l;54(1):328-43