Haemochromatosis

Question 1

What is haemochromatosis

Answer 1

Inherited autosomal recessive disorder leading to increased iron due to inreased intestinal absorption and release from bone marrow macrophages

Question 2

What gene does haemochromatosis affect and what mutation causes this

Answer 2

HFE gene
Mutation - C282Y or H63D

Question 3

Which combination of mutations are most and least likely to cause iron overload in haemochromatosis

Answer 3

C282Y/C282Y homozygous - 95% risk
C282Y/H63D -> 4% risk
H63D homozygous - least likely cause

Question 4

How is haemochromatosis identified clinically

Answer 4

Raised ALT
Abnormal liver imaging - fatty
Elevated serum ferritin

Question 5

Symptoms of haemochromatosis

Answer 5

Joint pain - esp hands and fingers
Fatigue
Mood disorders - depression, anxiety, mood swings
Hypogonadism
Other - abdo pain, palpitations, SOB, infertility, hair loss, amenorrhea

Question 6

What age does haemochromatosis present at

Answer 6

40-60 in men, post menopausal in women

Question 7

What does advanced haemochromatosis cause

Answer 7

Diabetes
Bronze skin
Hepatomegaly, cirrhosis, Arthropathy of 2nd and 3rd MCP joints
Cardiomyopahty + HF

Question 8

What is secondary haemochromatosis

Answer 8

Iron overlaod due to parenteral iron - multiple blood transfusions, IV iron, haemotological disorders - disease of erythropoieseis - ineffecitve accumulates iron
Over supplemetnation iron esp w vit C

Question 9

What is serum feerritin in haemochromatosis

Answer 9

15-200 (women) 300(men) = normal
Haemochromatosis = 1000s

Question 10

Why do you need transferrin saturation as well as ferritin

Answer 10

Ferritin is also raised in chronic alcohol abuse, NAFLD, inflam conditions + malignancy - acute phase protein raised

Question 11

What need for diagosis of haemochromatosis

Answer 11

Elevated serum ferritin and transferrin saturation + screen for genes
Assess for liver damage

Question 12

When need to exclude cirrhosis in haemochromatosis

Answer 12

Ferritin >1000

Question 13

Do you have haemochromatosis if you have the C282Y.C282Y homozygosity

Answer 13

No - have to also have raised iron
Can have genotype and not gene expresson
Monitor annually

Question 14

Treatment for haemochromatosis

Answer 14

Venesection

Question 15

Acute iron removal venesection how and goal

Answer 15

450ml blood removed
Goal to reduce SF 20-25ug/L
Continue until SF 50-100ug/L
12-18 monhts weekly
Then go to 2 weekly

Question 16

Maintenance venesection

Answer 16

2-4 per year - keep SF 50-100

Question 17

What acute phase reactant protein is affected by HFE

Answer 17

Hepicidin - regulates iron stores
HFE mutation decreases acitivity

Question 18

What is the pathophysiology of organ damage in haemochromatosis

Answer 18

Fenton reaction - Fe2+->Fe3+ releases hydroxyl free radicals -> oxidative damage - apoptosis

Question 19

Type I haemochromatosis

Answer 19

Only in white populations
90 cases

Question 20

Type 2 haemochromatosis when present

Answer 20

Juvenile - presents in early adulthood (20s+30s)

Question 21

What genes are type 2 haemochromatosis mutations caused by

Answer 21

2A - haemojuvelin gene
2B - hepicidn gene A

Question 22

What features are often more present in type 2 haemochromatosis

Answer 22

Hypogonadism
Cardiomyopathy

Question 23

Type 3 haemochromatosis

Answer 23

Transferrin receptor 2 mutation on chromosome 7, clincially same as HFE haemo

Question 24

Tyoe 4 haemochromatosis

Answer 24

4A - low transferin saturation and macrophage iron depositis
4B - clinical same as HFE haem.

Question 25

Diagnostix level for serum ferritin haemochromatosis

Answer 25

>674 picomols/L in men >449 in women

Question 26

Transferrin saturation in haemochromatosis level

Answer 26

>45%

Question 27

LFTs in haemochromatosis

Answer 27

Raised AST and ALT - likely not more than 2 x normal

Question 28

When refer to hepatology

Answer 28

Clinical evidence of liver involvement and/or serum ferritin >2247pmol/L must be referred to hepatology for liver biopsy to estimate hepatocyte iron content and assess extent of fibrosis or cirrhosis.

Question 29

Further investigations for complications of haemochromatosis

Answer 29

Fasting blood sugar ECG - arrhtymia, decreased QU=RS amplitude ECHO Testosterone, FSH, LH - low

Question 30

What hyperferritin conditions are differentials for HCT

Answer 30

Dysmetabolic hyperferritenmia Herditary aceruloplasminaemia - undetectable serum ceruloplasmin, ass with neuro symptoms

Question 31

What advice give to patinet with haemochromatosis

Answer 31

Avoid iron and iron-containing supplements Avoid vitamin C supplements (which increases the bioavailability of iron for enteric absorption), except in iron chelation therapy where it may increase therapeutic value Limit or avoid alcohol Consider hepatitis A and B vaccinations if no previous encounter.

Question 32

Stage 0 what is it and how foten monitor

Answer 32

Everything normal - monitor iron labs and symptoms every 3 years

Question 33

Stage 1 - what is and how often monitor

Answer 33

Transferrin sats >45%, normal ferritin, no symptoms Monitor 1 year

Question 34

Stage 2,3,4 haemochromatosis what is and management

Answer 34

Transferrin sats>45%, raised ferritin and/or clinical symptoms Venesection

Question 35

Goal for weekly venesection

Answer 35

<50% trasnferrin saturation can take several months

Question 36

What is iron chelation therapy indicated in

Answer 36

Stage2,3,4 haemochromatosis for wom venesection CI

Question 38

When is venesection CI

Answer 38

Anaemia, cardiac dsease, venous access issues

Question 39

Medication for haemochromatosis

Answer 39

Iron chelation therapy - deferasirox (oral), desferrioxamine)

Question 40

What does haemochromatosis increase the risk of

Answer 40

Susceptible to certain orangisms eg listeria monocytogenes Osteoporosis

Question 41

Why does haemochromatosis cause hypogonadism

Answer 41

Iron depositis in pituitary

Question 42

Liver transplant in haemochromatosis

Answer 42

Indicated for cirrhosis and cancer development but post-transplant prognosis (1- and 5-year survival) is significantly worse for haemochromatosis compared to other diseases that necessitate liver transplant