Hereditary Haemochromatosis

Question 1

what is it?

Answer 1

Primary iron overload, long-term excess iron absorption with parenchymal rather than macrophage loading
• Commonest form is due to mutations in HFE gene
• Decreases synthesis of hepcidin
• Increased iron absorption
• Results in gradual iron accumulation with risk of end-organ damage

Question 2

how does it present?

Answer 2

• Weakness/fatigue
• Joint pains
• Impotence
• Arthritis
• Cirrhosis
• Diabetes
• cardiomyopathy
• presentation usually in middle age or later – iron overload >5g

Question 3

how is it diagnosed?

Answer 3

• Risk of iron loading: transferrin saturation >50% (sustained on repeat fasting sample)‏
• Increased iron stores: serum ferritin >300 mg/l in men or >200 mg/l in pre-menopausal women
• Liver biopsy: rarely needed, non-invasive techniques such as Fibroscan available to assess for cirrhosis

Question 4

how is it managed?

Answer 4

•	Weekly venesection
- 450-500ml
- 200-250mg iron		
•	Initial aim to exhaust iron stores (ferritin <20 µg/l)‏
•	Thereafter keep ferritin below 50 µg/l
•	Family screening

Question 5

how is the family screening carried out?

Answer 5

o First degree relatives of cases, especially siblings (risk 1 in 4)
o Children – wait until they are adults able to give informed consent
o HFE genotype and iron status – ferritin and transferrin saturation
o Haemochromatosis may be asymptomatic until irreversible organ damage has occurred. This underlines importance of family studies – population screening remains controversial