Background to disease

Last update: 12/12/2007

OMIM 235200

Haemochromatosis is an autosomal recessive iron overload disorder caused by mutations in the HFE gene. Approximately 1 in 200 people are affected in Northern Europe and the carrier frequency is around 10%.

Characteristic clinical features include skin pigmentation, cirrhosis, arthropathy, diabetes mellitus, cardiomoypathy and primary liver cancer. Significant iron overload does not appear until middle age and men are more often affected than women. The main biochemical indicators that are used to make a clinical diagnosis before requesting a DNA test are raised blood iron and ferritin levels, or a family history of hereditary haemochromatosis.

There are 5 known point mutations in the HFE coding region: C282Y, H63D, S65C, I105T and G93R. C282Y and H63D are the most common HFE mutations. 91% of haemochromatosis patients in the UK are C282Y homozygotes.

The haemochromatosis phenotype is usually seen in C282Y homozygotes and rarely in H63D/C282Y compound heterozygotes. Compound heterozygotes with C282Y on one chromosome and S65C, G93R or I105T on the other chromosome could be affected but this is less common.

Laboratory Analysis

Analysis for this disease is now carried out by the Northern Genetics Laboratories under a reciprocal arrangement (GENLYNC). Please contact them directly regarding information regarding turnaround time and sensitivity. Local samples should still be sent via the Yorkshire Regional Genetic Laboratory where they will be forwarded as whole blood as appropriate. DNA from these samples can be stored in the Yorkshire Regional Genetic Laboratory if it is anticipated that future tests may be required (please indicate clearly on referral card if required).