Haemoachromatosis

Question 1

Haemachromatosis?

Answer 1

Iron overload

Question 2

What are the types of haemachromatosis?

Answer 2

Primary - Genetic (GH)

Secondary - Acquired - caused by events such as excessive blood transfusions or iron supplement overuse

Question 3

What is the main principle of GH?

Answer 3

Absorb too much iron (normally 2mg/day), in HC, absorb around 5-6mg/day - results in up to 20mg accumulation in the body

Question 4

What is the triad originally used to diagnose GH

Answer 4

Cirrhosis (Liver fibrosis)
T2D (Pancreas fibrosis)
Bronzing of skin (hyperpigmentation - increased haemosiderin and melanin production)

Question 5

What is the cause of organ damage in GH?

Answer 5

Fenton reaction - produces free radicals which cause damage to lipids (peroxidation), DNA, proteins. Forms a cycle where free radicals form react with non free radicals to form new free radicals

Question 6

What is the genetics behind GH?

Answer 6

Autosomal recessive mutation in the HFE gene (chromosome 6) - point mutation of Cytosine to Tyrosine at position 2 - C282Y - defective HFE - involved in gut absorption of iron and uptake into cell - exact mechanism unknown however thought to interact with the Transferrin receptor

Question 7

What percent of people with iron overload are homozygous for C278Y mutation?

Answer 7

60-93% - wide range due to varying diagnostics around world

Question 8

What is the disease progression in GH?

Answer 8

Mutation in the HFE gene
High plasma iron (increase transferrin saturation - TSAT)
High organ iron (increase in serum ferritin -SF)
Organ damage (greater than 1000mcg/L SF)

Question 9

What other factors affect disease progression?

Answer 9

Diet 
Alcohol intake
Infections
Pregnancy
Excess Bleeding
Low gene penetrance

Question 10

What are some of the signs/symptoms of GH?

Answer 10

Liver - fibrosis/scarring - cirrhosis
Pancreas - fibrosis - T2D
Heart - Cardiomyopathy (heart failure)
Arthralgia - joint pain
Chronic fatigue
Skin - bronzing

Question 11

How many years does it take for symptoms to develop?

Answer 11

40-60 years

Longer in pregnant women as they lose blood through menstrual cycle

Question 12

What are the measurements we can use for diagnosis of GH?

Answer 12

TSATS - transferrin saturation = SI/TIBC - variable throughout day (greater than 40%F 50%M indication of potential GH)

SF - proxy measure for build up on iron in the tissues - >300mcg/L indication - affected by infection and inflammation (acute phase reactant)

Use both? - genetic typing?

Question 13

What algorithm was developed to diagnose GH?

Answer 13

NZ -
TSAT >40%
SF >1000mcg/L
Family history of GH

May miss subclinical GH

Question 14

How can we manage GH?

Answer 14

Phlembotomy - remove around 500ml of blood a week until Hb levels return to normal level - use TSATS and SF to indicate normal iron levels - continue 4 times a year after. Effective, cheap, simple

Diet changes - reduce vit C (increases iron absorption), avoid red meat, reduce alcohol (iron and alcohol synergistic hepatoxin), avoid shellfish (vibrio vilnicifius)

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