Haemochromatosis

• What is hereditary haemochromatosis?


  It is a disorder of iron metabolism resulting in excessive iron accumulation in the body.
• What are the key signs and symptoms of hereditary haemochromatosis?


  Bronze skin, type 2 diabetes mellitus, fatigue, joint pain, liver cirrhosis, and adrenal insufficiency.
• What are the key investigations for hereditary haemochromatosis?


  Blood tests, genetic testing, and MRI imaging of the brain and heart.
• What is the primary management strategy for hereditary haemochromatosis?


  Iron depletion, primarily through phlebotomy or venesection and the use of desferrioxamine.
• What characterizes hereditary haemochromatosis?


  Excessive iron accumulation in the body with deposition in various sites.
• In which populations is hereditary haemochromatosis most common?


  People of Northern European descent, particularly those of Celtic origin.
• What is the estimated prevalence of hereditary haemochromatosis in the UK?


  Approximately 1 in 200 individuals of Northern European ancestry.
• What is the most common genotype associated with hereditary haemochromatosis?

  Homozygosity for HFE C282Y on chromosome 6.
• How does the HFE C282Y mutation affect iron metabolism?


  It disrupts the control of iron absorption, leading to excessive iron accumulation.
• What are the signs and symptoms of hereditary haemochromatosis?


  • Bronze skin
  • Type 2 diabetes mellitus
  • Fatigue
  • Joint pain
  • Sequelae of chronic liver disease/cirrhosis
  • Adrenal insufficiency
  • Testicular atrophy
• What are the differential diagnoses for hereditary haemochromatosis?


  • Wilson's disease: liver disease, neurological symptoms, Kayser-Fleischer rings
  • Alpha-1 antitrypsin deficiency: lung disease, panniculitis, liver disease
  • Porphyria cutanea tarda: skin blistering, hyperpigmentation, liver abnormalities
• What blood tests are used for screening hereditary haemochromatosis?


  • Iron studies: raised transferrin saturation (>55% in women, >50% in men)
  • Raised ferritin, raised iron, low TIBC
  • Note: Ferritin is an acute phase reactant, most helpful in early disease
• What imaging techniques are used to investigate hereditary haemochromatosis?


  MRI imaging of the brain and heart to identify evidence of iron deposition.
• What is the purpose of a liver biopsy in hereditary haemochromatosis?


  To confirm increased iron stores, with Perl's stain quantifying the level of iron loading.
• What are the management strategies for hereditary haemochromatosis?


  • Phlebotomy or venesection to stimulate erythropoiesis and mobilize iron
  • Administration of desferrioxamine, an iron chelating agent
  • Avoidance of undercooked seafood to prevent bacterial infections
• What are the reversible and irreversible complications of hereditary haemochromatosis?


  Reversible complications:

  • Dilated cardiomyopathy
  • Bronze skin

  
  

  Irreversible complications:

  • Cirrhosis
  • Diabetes mellitus
  • Hypogonadotropic hypogonadism
  • Arthropathy