Iron Overload

Question 1

What is the clinical definition of iron overload?

Answer 1

-Serum ferritin >1000mg/ml with inflammation OR serum ferritin >2500mg/ml in the absence of inflammation

Question 2

What are the main causes of iron overload?

Answer 2

• Primary (Genetic haemochromatosis)
  - Disorder of iron haemostasis
  - Types 1-4 (e.g, type 1: mutations in HFE gene)
  - Secondary
  - Basically, any form of iron overload, through multiple mechanisms
  - Transfusion
  - Increased absorption due to ineffective erythropoiesis
  - (eg Beta thal, other anaemias)
  - Excessive iron administration, oral or parenteral

Question 3

Outline the investigation and assessment of iron overload

Answer 3

• Serum ferritin is measured as an indirect indicator of iron storage
• Correlation with LIC varies in transfusional and non-transfusional iron overload
  - Liver iron concentration (LIC) on biopsy
  - Reflects total body iron but may not accurately indicate cardiac iron status
  - Evaluation of liver and cardiac iron by MRI (Or ‘SQUID’, whatever that is)
  - General tests of organ function

Question 4

Outline the treatment and monitoring of iron overload

Answer 4

• Monitoring: Serum ferritin, LIC, MRI
  - Primary iron overload (Genetic haemochromatosis):
  - Removal of excess iron by phlebotomy
  - To maintain tf saturation <50%
  - Secondary iron overload:
• Monitoring:
• Keeping record of the volume or weight of the administered units.
• The haematocrit of each unit given, or an average
• The patient’s weight is also monitored
  - Iron chelation therapy: (eg deferiprone)

Question 5

-How iron is metabolised?

Answer 5

• Dietary iron enters duodenal enterocytes
  - Ferrous iron enters the cytoplasmic iron pool
  - Iron enters the systemic circulation via ferroportin
• Transferrin is the major iron-carrying protein. Iron remains bound to this in circulation. IT’s called TBI (Transferrin-bound iron)
• TBI is taken up into cells by TfR1 (transferrin receptor 1)
  - Non-transferrin-bound iron (NTBI) increased when iron increases
• This is imported by DMT1 and converted to Fe2+ by DCYTB (duodenal cytochrome B)

Question 6

In what diseases is measuring serum ferritin not reliable?

Answer 6

-Sickle cell disease and viral hepatitis

Question 7

List some causes of haemochromatosis

Answer 7

(Inherited)
-C282Y mutation of HFE gene (Leads to reduced hepcidin release)
-HJV mutation (In juvenile haemochromatosis. leading to reduced hepcidin release)
(Acquired)
-Iron overload from transfusion