Haemochromatosis

Question 1

Haemochromatosis

Answer 1

This 52‐year‐old man was referred after a diagnosis of diabetes mellitus was made by his GP. Please examine him and discuss further investigations.

Question 2

Clinical signs

Answer 2

• Increased skin pigmentation (slate‐grey colour)
• Stigmata of chronic liver disease (general, hand, face, chest and abdomen)
• Hepatomegaly

Question 3

Scars

Answer 3

• Venesection
• Liver biopsy
• Joint replacement
• Abdominal rooftop incision (hemihepatectomy for hepatocellular carcinoma)

Question 4

Evidence of complications

Answer 4

• Endocrine: ‘bronze diabetes’ (e.g. injection sites), hypogonadism and testicular atrophy
• Cardiac: congestive cardiac failure
• Joints: arthropathy (pseudo‐gout)

Question 5

Inheritance

Answer 5

• Autosomal recessive on chromosome 6
• HFE gene mutation: regulator of gut iron absorption
• Homozygous prevalence 1:300, carrier rate 1:10
• Males affected at an earlier age than females - protected by menstrual iron losses

Question 6

Presentation

Answer 6

• Fatigue and arthritis
• Chronic liver disease
• Incidental diagnosis or family screening

Question 7

Investigation

Answer 7

For diagnosis: 
• ↑ Serum ferritin
• ↑ Transferrin saturation
• Liver biopsy (diagnosis + staging)
• Genotyping

And consider: Look for complications
• Blood glucose – Diabetes
• ECG, CXR, ECHO – Cardiac failure
• Liver ultrasound, α‐fetoprotein – Hepatocellular carcinoma (HCC)

Question 8

Treatment

Answer 8

• Regular venesection (1 unit/week) until iron deficient, then venesect 1 unit, 3–4 times/ year
• Iron deficient means: Transferrin saturation < 50%, and S. ferritin < 50mcg/L
• Avoid alcohol
• Surveillance for HCC (US & AFP)

Question 9

Family screening (1st degree relatives aged > 20 years)

Answer 9

• Iron studies (ferritin and TSAT)
If positive:
• Liver biopsy
• Genotype analysis

Question 10

Prognosis

Answer 10

• 200 × increased risk of HCC if cirrhotic
• Reduced life expectancy if cirrhotic
• Normal life expectancy without cirrhosis + effective treatment

Question 11

Reversible and Irreversible effects of haemochromatosis

Answer 11

Irreversible:
- Cirrhosis
- DM
- Arthritis
- testicular atrophy
Reversible:
- hepatomegaly
- Skin color
- cardiomyopathy