Iron Overload

Question 1

primary cause of iron overload

Answer 1

haemochromatosis

Question 2

genetics of haemochromatosis

Answer 2

mutation in the HFE gene (C282Y and H63D) on chromosome 6

Question 3

what does the mutation in haemochromatosis cause?

Answer 3

decreased hepcidin synthesis causing increased absorption resulting in gradual accumuation of iron and end organ damage

Question 4

presentation of haemochromatosis

Answer 4

middle age or later
weakness/ fatigue
joint pains
impotence
cardiomyopathy
arthritis, cirrhosis, diabetes

Question 5

diagnosis of haemochromatosis

Answer 5

iron >5g
transferrin saturation >50%
serum ferritin >300ug/l in men or >200ug/l in women
liver biopsy stain
family screening

Question 6

why is family screening important in haemochromatosis?

Answer 6

asymptomatic condition until end organ damage

Question 7

management of haemochromatosis

Answer 7

weekly venesection, aim to exhaust ferritin <20ug/l

Question 8

secondary causes of iron overload

Answer 8

transfusions

iron loading anaemias (ineffective erythropoiesis)

Question 9

examples of iron loading anaemias (ineffective erythropoiesis)

Answer 9

thalassaemia
sideroblastic anaemia
refractory hypoplastic anaemia (red cell aplasia and myelodysplasia)

Question 10

management of secondary iron overload

Answer 10

iron chelating options e.g. desferrioxamine (SC/IV), deferiprone, deferasinox

can’t venesect as already anaemic

Question 11

what is sideroblastic anaemia?

Answer 11

excess iron build-up in mitochondria due to failure to incorporate iron into haem

Question 12

causes of sideroblastic anaemia

Answer 12

1. hereditary

2. acquired (MDS, lead poisoning, alcohol excess)

Question 13

blood film of sideroblastic anaemia

Answer 13

produces sideroblasts