Haemochromatosis

Question 1

What is Haemochromatosis?

Answer 1

Increased intestinal absorption of iron causes accumulation of iron in tissues, which may lead to organ damage.
Iron deposition in joints, liver, heart, pancreas, pituitary, adrenals + skin

Question 2

Describe the aetiology of Haemochromatosis

Answer 2

Autosomal recessive
Caused be a defect in the HFE gene
Genetic penetrance is complex; not everyone who is homozygous develops the clinical disease

Question 3

Describe the epidemiology of Haemochromatosis

Answer 3

RARE
More frequent in middle aged M than F
Tends to present later in F (menstrual blood loss protective)

Question 4

List 6 early signs and symptoms of Haemochromatosis

Answer 4

Fatigue  
Weakness  
Lethargy  
Arthropathy 
Erectile dysfunction  
Heart problems

Question 5

How may Haemochromatosis present?

Answer 5

Often ASYMPTOMATIC until late stages of the disease
Symptoms usually start between 40-60 yrs
May be an incidental finding (e.g. LFTs, serum ferritin)

Question 6

List 7 late signs and symptoms of Haemochromatosis

Answer 6

Diabetes mellitus  
Bronzed skin: GREY/brown with slate-grey patches in the mouth 
Hepatomegaly 
Cirrhosis  
Hypogonadism: Amenorrhoea, Impotence 
Cardiac: arrhythmias + cardiomyopathy  
Neurological + psychiatric problems

Question 7

Describe haematinic results in Haemochromatosis

Answer 7

Serum ferritin HIGH
TIBC LOW
Transferrin LOW
Transferrin saturation HIGH

Question 8

What are the other blood measurements in Haemochromatosis?

Answer 8

AST + ALT HIGH

FSH, LH, Testosterone LOW (secondary hypogonadism)

Question 9

What other investigations may be performed in Haemochromatosis?

Answer 9

Genetic testing e.g. HFE mutation analysis
Liver MRI: sensitive, specific, non-invasive, measures iron content
ECHO if cardiomyopathy suspected
Bone Densitometry: if concomitant RF to osteoporosis

Question 10

Describe the pathophysiology of haemochromatosis

Answer 10

Iron absorbed in duodenum
Stored intracellullarly bound to ferritin or transported out of the cells by ferroportin, then binds to transferrin in the blood.
Hepcidin inhibits ferroportin, thereby regulating amount of iron entering blood.
90% of HH due to mutation causing a deficiency of hepcidin, resulting in unregulated absorption of iron

Question 11

Why is serum ferritin measurement not very specific?

Answer 11

Its an acute phase protein

Question 12

What must be remembered when interpreting serum iron and transferrin saturation?

Answer 12

They DON’T accurately reflect total body iron stores

Question 13

Describe the stereotypical patient presenting with haemochromatosis

Answer 13

Bronze-coloured diabetic with jaundice ~40-60yrs old

Question 14

What is the most sensitive and specific way of measuring liver iron content? What other benefits does this investigation have?

Answer 14

Biopsy

Can assess for liver damage (cirrhosis/ fibrosis)