Haemochromatosis

Exam Cram

• Haemachromatosis: genetic mutation (C282Y) causes by iron accumulation

• Presentation: arthralgia, polyuria, skin darkening, "bronze diabetes", erectile dysfunction

• Investigations: raised tranferrin & ferritin; deranged LFTs

• Diagnosis: 

  • 1. Genetic testing usually sufficient, 

    2. Liver biopsy if uncertainty

• Management: blood letting (venepuncture)

Outline 

Background

• Gene: HFE C282Y heavily implicated, autosomal recessive, discovered in 1996

• Gene defect causes damage to hepcidin, implicated in iron metabolism

• Prognosis: if diagnosed early with prompt treatment, life expectancy is normal

Assessment

History

• Lethargy, arthraliga (PseudoGout), abdo pain

• Erectile dysfunction

Examination

• Bronze / tanned skin

Investigations

• Raised ferritin

• Transferrin > 45%

• XR: chondrocalcinosis

• Genetic testing: C282Y & H63D

• Biopsy: iron accumulation

Diagnosis

• Diagnostic criteria: symptoms + raised ferritin + genetic abnormality

• Differentials: alcohol abuse can cause chronically high ferritin

• Classification

  • (Primary) Hereditary Haemachromatosis

  • Secondary- excessive iron (multiple blood transfusions)

    • Anaemia

      • Sickle Cell Disease

      • Thalassemia

      • Bone marrow failure (e.g. CLL)

      • CKD- EPO reduced rates of haemochromatosis

    • Liver Cirrhosis

      • ALD

      • HBV, HCV

Management

• Venipuncture starts weekly, then two weekly

• Gastroenterology follow up

Med Reg Notes

Hereditary Haemochromatosis

80% homozygous HFE C282Y mutation

Mutation prevalence 1/250 in Northern Europe

5% C282Y/ H63D genes

C282Y homozygous has variable penetrance and can have no clinical significance. 

Complications

• Arthropathy

• Chondrocalcinosis

• Congestive Heart Failure (CHF) 

• Erectile Dysfunction 

• Porphyria cutaenous tarda

Complications: liver, pancreas, heart, joints, skin & gonads. 

Resources and References

1. https://www.nhs.uk/conditions/haemochromatosis/

2. https://www.haemochromatosis.org.uk/?gad_source=1&gclid=CjwKCAiAtsa9BhAKEiwAUZAszQALaR8zioh08f4uNVJccwT5CNgwhtvpUfSZH_Z2xQz6kluNoj-dnxoCCFkQAvD_BwE

3. https://bjgp.org/content/63/611/331

4. https://www.niddk.nih.gov/health-information/liver-disease/hemochromatosis/symptoms-causes

Page written in 2025.