Haemochromatosis

• Inherited (autosomal recessive) occurring in up to 0.5% population (N. Europe).

• Haemochromatosis locus is tightly linked to the HLA locus on chromosome 6p and up to 10% population are heterozygous.

• Single missense mutation found in the homozygous state in 80% of patients.

• The gene designated HFE is an MHC class Ib gene.

• Homozygotes develop symptomatic iron overload.

Caused by failure to regulate iron absorption from bowel causing progressive increase in total body iron. Parenchymal accumulation occurs initially in liver then pancreas, heart, skin and other organs rather than RE sites. Symptoms do not usually develop until middle age when body iron stores of >15—20g have accumulated. Environmental factors (e.g. alcohol use in males and menstruation in females) affect rate of accumulation and age at presentation. Clinical expression of haemochromatosis is seen 10x more commonly in 9 Only 25% of heterozygotes show evidence of minor increases in iron stores and clinical problems do not occur.

Clinical manifestations of iron overload only occur in homozygotes and presentation as 'bronze diabetes' is characteristic.

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