Hereditary haemochromatosis

05/11/03 By Richard Twyman

Hereditary haemochromatosis is also known as iron overload disease. It is an inherited disorder in which iron accumulates in the blood because too much is absorbed by the intestines.

The iron is deposited in various parts of the body, including the liver, pancreas, heart and joints. The disease affects about 1 in 400 people. It can be treated by the regular removal of blood until iron levels return to normal.


Hereditary haemochromatosis is a single gene disorder most often caused by a faulty gene on chromosome 6. This gene is named HFE, and its product is a membrane-spanning protein found in the cells of the duodenum, the part of the intestine where iron is absorbed. Its function is to regulate the uptake of iron.

See the HFE gene in the interactive chromosome browser [requires Flash]

Two different mutations in the HFE gene have been shown to be associated with over 93 per cent of HHC cases. About 77.5 per cent of affected individuals have two copies of the C282Y mutation, one inherited from each parent, while about 4 per cent have a single copy of the mutation and one normal HFE gene. Approximately 6.5 per cent have either one or two copies of the second mutation, which is called H63D, while a further 5 per cent are known as compound heterozygotes and have one copy of each mutation. The remaining 7 per cent of cases are likely to involve different mutations in HFE, or mutations in other genes.


Early symptoms of hereditary haemochromatosis include fatigue, weakness, impotence and pain in the abdomen and joints, but many people are unaware they have the disease until advanced stages. Ultimately, the disease can lead to liver cirrhosis, diabetes mellitus, heart disease, arthritis, increased pigmentation of the skin, and shrinking of the pituitary gland and gonads. If left untreated, between one-third and one-half of affected individuals die of liver cancer.

The symptoms differ between men and women, with men more likely to present with liver disease and women more likely to present with fatigue and arthritis. These differences may be attributable to women having a lower iron intake than men and losing iron through menstruation, pregnancy and lactation.


Hereditary haemochromatosis can be detected even before the onset of symptoms using the transferrin saturation (TS) test, which measures the level of iron in the serum against the body's capacity to store iron. If saturation is over 55 per cent, this may indicate iron overload and the test should be repeated after an overnight fast. A serum ferritin (SF) test may also be carried out at this point. This measures the level of a blood protein called ferritin whose function is to store iron. As the amount of iron in the blood increases, so does the amount of ferritin. Where the TS and SF tests both suggest iron overload, blood cells can be tested for mutations in the HFE gene.


The treatment for hereditary haemochromatosis is very simple: blood is removed from the body at regular intervals. This has the effect of reducing the number of red cells, which are full of the iron-containing protein hemoglobin. The body then makes new red cells from bone marrow, and calls on its iron reserves to make hemoglobin.

Depending on how far the disease has progressed, up to a pint of blood may be removed every week until iron levels return to normal. The therapy is then repeated every few months to make sure iron levels remain at safe levels. The severe symptoms of prolonged iron overload cannot be reversed by this treatment but they can be managed more effectively. Supplements of iron and vitamin C (which promotes iron absorption) are to be avoided.

Share |
Icon representing the Single gene disorders section.
Wellcome Trust, Gibbs Building, 215 Euston Road, London NW1 2BE, UK T:+44 (0)20 7611 8888