Haemochromatosis

Outline 

Background

• Gene: C282Y variant on HFE gene is 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

• 'Iron fist': thickening & swelling of first and second MTP joint

Investigations

• Raised ferritin & Transferrin > 45%

• XR: chondrocalcinosis

• Genetic testing: C282Y & H63D

• Liver Biopsy: iron accumulation

Diagnosis

• Diagnostic criteria: (3)

  • • Symptoms 

    • Raised ferritin 

    • Genetic abnormality (liver biopsy can be useful if diagnostic uncertainty)

• 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

• Venepuncture starts weekly, then two weekly

• Gastroenterology follow up

• Testosterone injections if low 

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) 

• Hypogonadism: Erectile Dysfunction 

• Porphyria cutaenous tarda

Arthropathy

Arthropathy is the single most prevalent symptom patients present with in haemachromatosis. Ancedotally treatment of the underlying cause is the most effective management. Paracetamol, ibuprofen, orthotics, PT and OT input can trialled. 

Iron overload in Anaemia

This is common in haematological malignancies and can be managed with iron chelation. 

Future Research

NHS Genomic Sequencing

The NHS aims to offer genomic sequencing to newborns by 2030, which could revolutionalise Hereditary Haemochromatosis. Early diagnosis could lead to prompt venesection and prevention of their complications. 

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.