Haemochromatosis

Question 1

What is haemochromatosis?

Answer 1

An autosomal-recessive disorder resulting in dysregulated dietary iron absorption and increased iron release from macrophages leading to iron overload.

Question 2

What is the epidemiology of haemochromatosis: Carrier? Age? Ethnicity? Gender?

Answer 2

Carrier frequency in up to 1 in 10. Age of presentation: 40-60. Primarily in those of northern Europe descent. Mutation has no equal gender distribution, but men have higher prevalence and severity of clinical disease.

Question 3

What is a suggested reason for decreased prevalence/severity in women?

Answer 3

Menstruation is protective.

Question 4

What is the aetiology and pathophysiology of haemochromatosis?

Answer 4

Autosomal recessive disorder. Characterised by HFE mutation on Chr6. Most common mutations are C282Y and H63D. This causes intestinal absorption of iron to increase (normally, HFE facilitates the binding of transferrin (iron’s carrier protein in the blood). HFE mutation creates a strong transferring signal as if the body were deficient in iron). Iron is initially stored as ferritin but deposited as haemosiderin in high levels which is toxic – leading to symptoms of haemochromatosis.

Question 5

What are the types of haemochromatosis? (x4)

Answer 5

1. Type 1: hereditary (HFE genotype) – recessive and present in only white populations
2. Type 2: juvenile – associated with mutations in the hemojuvelin and hepcidin genes
3. Type 3: transferrin receptor 2
4. Type 4: ferroportin disease

Question 6

What are the symptoms and signs of haemochromatosis? (x8)

Answer 6

• Fatigue
• Weakness
• Arthralgias such as knee pseudogout and osteoarthritis-like symptoms of the second and third MCP joints.
• Hepatomegaly: usually associated with cirrhosis. You may also see signs of liver disease such as clubbing and leukonychia.
• Diabetes mellitus associated with cirrhosis and iron deposition in pancreas
• Erectile dysfunction and fall in libido – will see testicular atrophy, loss of hair, gynaecomastia
• Bronze skin or later-stages associated with slate-grey skin pigmentation (increased melanin deposits)
• Congestive heart failure: from iron infiltration in heart. May observe arrythmias.

Question 7

What are the blood investigations for haemochromatosis? (x5)

Answer 7

• Serum transferrin saturation: elevated; higher than 45%
• Serum ferritin: elevated
• LFTs: aminotransferase levels high from fibrosis
• Blood glucose: raised
• Testosterone/FHS/LH: lower

Question 8

What are the other investigations for haemochromatosis? (x4)

Answer 8

• LIVER BIOPSY: most sensitive and specific test for measuring liver iron content and also allows for assessment of liver damage
• MRI liver: measure iron content
• Echocardiogram: to assess end-organ heart damage; specifically, cardiomyopathy
• Bone densitometry: assess osteoporosis

Question 9

What are the complications of haemochromatosis? (x4)

Answer 9

Cirrhosis, hepatocellular cancer, diabetes, dilated cardioyopathy.