Hereditary Haemochromatosis

Question 1

What is hereditary haemochromatosis

Answer 1

Genetic iron metabolism disorder where increased intestinal iron absorption results in deposition in organs

Question 2

Hereditary haemochromatosis genetics

Answer 2

HFE gene with C282Y or H63D mutation

A signficant proportion of C282Y homozygotes don’t develop iron overload

Question 3

Hereditary haemochromatosis presentation

Answer 3

Menstrual blood loss is protective so presents later in women
Early: Tiredness, arthralgia and decreased libido if anything
Later: Grey skin, signs of chronic liver disease, dilated cardiomyopathy
May present with endocrinopathies e.g. DM from iron deposition in pancreas, hypogonadism from pituitary dysfunction

Question 4

Hereditary haemochromatosis tests

Answer 4

Inc LFTs, ferritin and transferritin saturation
Confirmed with HFE genotyping

Chondrocalcinosis upon imaging, liver and cardiac MRI shows iron overload
Liver biopsy with Perl’s staining quantifies iron loading and disease severity

Question 5

Hereditary haemochromatosis management

Answer 5

Venesection (drawing blood therapeutically) 0.5-2 units/1-2 weeks until ferritin <50µg/L; then maintenance venesection for life
Desferrioxamine chelation if intolerant of venesection
No need to avoid iron rich foods but avoid alcohol, uncooked seafood and OTC iron supplements
Screening for 1st degree relatives

Question 6

Hereditary haemochromatosis prognosis

Answer 6

Venesection returns back to normal if non-diabetic and non-cirrhotic
If cirrhotic, 22-30% get HCC

Question 7

Hepcidin in iron metabolism

Answer 7

Negative regulator of intestinal iron absorption, defects in negative feedback regulation by iron levels can result in a rare haemochromatosis