Haemochromatosis

Question 1

Define haemochromatosis

Answer 1

An inherited disorder of iron metabolism in which an increase in intestinal absorption leads to iron deposition in joints, liver, heart, pancreas, pituitary, adrenals and skin.

Multisystem disorder or dysregulated dietary iron absorption and increased iron release from macrophages.

Question 2

Aetiology of haemochromatosis

Answer 2

Autosomal recessive disorder, mutation in hepcidin protein
The gene responsible for most HH is HFE (short arm chromosome 6).
Most common mutation = C282Y

Question 3

Risk factors for haemochromatosis

Answer 3

Male sex (more frequently and severely affected)
Middle age
White ancestry
Family history
Supplemental iron

Question 4

Symptoms and signs of haemochromatosis

Answer 4

Non-specific symptoms: Weakness | Fatigue | Lethargy | Abdominal pain
Liver: Symptoms of Liver disease | Hepatosplenomegaly | Liver cirrhosis | ­higher risk of hepatocellular carcinoma
Pancreas: Symptoms of Diabetes mellitus | Malabsorption
Joints: Joint pain (most commonly 2nd/3rd metacarpophalangeal joint)
Gonads: Hypogonadism: testicular atrophy, loss of hair, gynaecomastia, amenorrhea
Heart: Cardiac failure | Cardiomyopathy ( Arrhythmia)
Skin: “Slate-grey” pigmentation (due to ­ melanin deposits) / Bronze pigmentation

Question 5

Stages of haemochromatosis according to time

Answer 5

Early
- Nil, OR:
- Tenderness, arthralgia (2nd, 3rd MCP joints + knee), reduced libido
- Weakness
- Fatigue
- Lethargy

Later
- Slate grey skin pigmentation / tan

Endocrinopathies
- DM (bronze diabetes)
Hypogonadism from reduced pituitary functio

Question 6

Investigations for haemochromatosis

Answer 6

Iron studies:
- Transferrin raised (>45%), transferrin saturation raised
- Ferritin raised (>200 males, >150 females)
- TIBC reduced
- Iron raised
LFTs: AST/ALT raised
Fasting blood glucose
Testosterone/LH/FSH: reduced
HFE mutation testing

LIver/cardiac MRI
Echo
X-ray: Linear calcification (chondrocalcinosis)
Liver biopsy: Perl’s stain/prussian blue stain to quantify iron loading and assess severity

Question 7

Management for haemochromatosis

Answer 7

Conservative:
- Avoid iron/iron-containing supplements
- Avoid vitamin C supplements
- Avoid excess alcohol
- Hep A/B vaccination

First line: venesection
- monitoring adequacy of venesection: transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/l
Second line: desferrioxamine (chelation)

Question 8

Complications of haemochromatosis

Answer 8

Cirrhosis
Diabetes mellitus
Chronic congestive heart failure
Hepatocellular carcinoma
Hypogonadism
Bone loss
Infectious

Question 9

Prognosis for haemochromatosis

Answer 9

Mean survival 21 years
Patients with haemochromatosis have increased risk of dying from cancer (11%), especially hepatocellular carcinoma (7%), diabetes mellitus (2%), cardiomyopathy (2%), myocardial infarction (2%), and liver cirrhosis (6%)