Hereditary Haemochromatosis

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• Inherited disorder of iron metabolism

• Increased intestinal iron absorption leads to its deposition in multiple organs

• joints, liver, heart, pancreas and pituitary

• Middle-aged males are more frequently and severely affected than women, in whom the disease tends to present about 10 yrs later (menstrual blood loss is protective)


Genetics:

• One of the commonest inherited diseases of North Europeans, especially Celtics

• Carrier rate of 1 in 10 and homozygosity frequency of 1:200-1:400

• Gene responsible (for most) = HFE

• 2 major mutations - C282Y (60-100%)

H63D (3-7%)

• Compound heterozygotes 1-4 %


Clinical:

• Asymptomatic early on

• Then tiredness and arthralgia (MCP and large joints)

• Later -> 

• slate-grey skin pigmentation

• DM (bronze diabetes)

• signs of chronic liver disease

• hepatomegaly

cirrhosis

• cardiac failure (dilated cardiomyopathy)

• hypogonadism (pituitary dysfunction or via cirrhosis) and associated osteoporosis.  Others include hyporeninaemic hypoaldosteronism


Tests:

Bloods:

• Abnormal LFTS

• Serum Ferritin UP, Serum Iron UP, Total Iron binding capacity DOWN, Transferrin saturation > 80%

• HFE genotyping

Joint X-Rays:

• Liver Biopsy:

• Perl's Stain quantifies iron loading (hepatic iron index >1.9microm/kg/yr) and assesses disease severity

MRI - estimate hepatic iron loading

• ECG and Echo - cardiomyopathy


Management:

Venesect - 1 unit/wk until mildly Fe-deficient.  Then 1 unit every 2-3/12 for life.  Haematocrit <0.5, ferritin <100, TIBC >50 and transferring sat <40%


Prognosis:

• Venesection returns life expectancy to normal if non-cirrhotic and non-diabetic

• Arthropathy may improve or worsen

• Gonadal failure is irreversible

• In non-cirrhotic patients, venesection may improve liver histology

• Cirrhotic patients have a >10% chance of HCC (22%-30%)

• Being > 50 years 13 x risk

• Being HBsAg +ve 5 x risk

• Alcohol abuse 2 x risk


Secondary Haemochromatosis