haemochromatosis

Question 1

definition of haemochromatosis

Answer 1

inherited disorder of Fe metabolism - increased intestinal Fe absorption = iron deposition in joints, liver, heart, panc, pituitary, adrenals, and skin

may lead to organ damage

Question 2

epidemiology of haemochromatosis

Answer 2

one of the commonest inherited conditions in those of Northern European (especially Celtic) ancestry

(carrier rate of ~1 in 10 and a frequency of homozygosity of ~1 in 200–400)

40-60yrs

females later onset and less severe presentation as a result of iron loss through menstruation

Question 3

sx of haemochromatosis

Answer 3

early

• none
• tiredness
• arthralgia 2nd and 3rd MCP joints and knee pseudogout

fatigue

weakness

lathargy

impotence

loss of libido

skin pigmentation

abdo pain

later symptoms

• small/large joint pain - second/third metacarpophalangeal joints
• symptoms of liver disease
• dm
• hypogonadism
• cardiac failure
• Exclude causes of secondary iron overload (e.g. multiple transfusions)

Question 4

signs of haemochromatosis

Answer 4

RF

hepatomegaly/hepatosplenomegaly

dm

slate-grey skin pigmentation from increased melanin deposits

signs of chronic liver disease

cirrhosis - especially if drink alcohol

dilated cardiomyopathy

dm (bronze dm - from deposition of iron in panc)

hypogonadism from reduced pituitary dysfunction - testicular atrophy, loss of hair, gynaecomastia

signs of HF/arrhythmias

Question 5

aetiology of haemochromatosis

Answer 5

gene responsible in most cases is HFE on chromosome 6p

the 2 commonest mutations are termed C282Y and H63D.

C282Y accounts for 60–90% of HH, and H63Daccounts for 1–3%, with compound heterozygotes accounting for 4–7%.

Penetrance is variable—a significant fraction of C282Y homozygotes will not develop signs of iron overload during follow-up, complicating screening decisions.

Question 6

models of haemochromatosis

Answer 6

liver - HFE deficiency = reduced expression of hepatic hormone hepcidin = increased duodenal iron absorption through lack of inhib effect of hepcidin on ferroprotin (exports Fe from enterocytes into circulation)

crypt cell - The HFE protein interacts with the transferrin receptor 1 in duodenal crypt cells

• mutation in HFE may impair the uptake of transferrin-bound Fe into crypt cells = upregulation of Fe transporter DMT1 in the crypt cells as they migrate up the villous and mature into enterocytes = increased iron absorption

Question 7

RF for haemochromatosis

Answer 7

middle aged men more frequently and severely affected than women, in who disease presents approx 10yrs later (menstrual blood loss is protective)

white

FH

supplemental iron

Question 8

Ix for haemochromatosis

Answer 8

blood

imaging

liver biopsy - using Perl’s stain quantifies iron loading and assesses disease severity

gene typing for HFE

pancreas - fasting/random blood glucose to test for dm

pit func test - reduced testosterone in men, reduced/inappropriately normal LH, FSH (ie secondary hypogonadism), 9am cortisol, TFTs, IGF-1

heart ECG, echo

joint xr - linear calcification (chondrocalcinosis)

Question 9

imaging for haemochromatosis

Answer 9

chondrocalcinosis

liver and cardiac MRI - Fe overload

Question 10

bloods for haemochromatosis

Answer 10

raised LFT

raised ferritin - male>200/female>150ng/mL; but inflammation will also raise ferritin

increased transferrin saturation

raised Fe

low TIBC

Question 11

mx of haemochromatosis

Answer 11

• avoid iron
• avoid vit C (increases fe absorption)
• avoid alcohol
• consider hep A B vaccines

phlebotomy
1. induction - weekly to get transferritin sats < 50
2. maintanance - less than monthy

iron chelation therapy if phlebotomy CI - deferasirox or desferrioxamine

liver transplant

Question 12

CI to phlebotomy for haemochromatosis

Answer 12

• anaemia,
• cardiac disease
• venous access issues