Hereditary Haemochromatosis

What is Hereditary Haemochromatosis (HH)? This is the most frequently inherited (genetic) disorder in the Caucasian population. The disease is characterised by massive amounts of iron being accumulated in the body risking damage to the liver, pancreas, heart, joints and endocrine glands, and often causing diabetes, gonadal failure and pigmentation of the skin. The normal amount of total iron in an adult is approximately 3.5 grams mainly carried as haemoglobin in the blood or stored as ferritin and used by the body for its growth. If the excess iron is left to accumulate for a long time, organ damage will occur and when diagnosed at a later age (at 40-50 years of age) irreversible damage to the organs would have already caused serious consequences. Haemochromatosis can also be acquired in association with related medical problems. Who is likely to get Hereditary Haemochromatosis? Genetic diseases are often more common in specific community groups. HH is most common amongst white North Europeans. About 10% i.e.1 in 10 Caucasians are carriers (heterogeneous) of the faulty gene (mutation) and are mostly unaffected by the disorder. Approximately 1 person in 250 will inherit a 'double dose' (homozygous) of the faulty gene and 85 % of these will develop a severe form of the disease, the detection of which may occur as late as middle age, by which stage organ damage has most probably already occurred. What causes Hereditary Haemochromatosis? Hereditary Haemochromatosis is a result of an inborn error of metabolism and is caused by inheriting a 'double dose' of a faulty gene (HFE), which causes massive amounts of iron to accumulate in the body. Diagnosis is easily made by testing the degree of iron storage levels in the blood (Serum Ferritin) and the level of iron in the blood (Transferrin Saturation Concentration). Confirmation of diagnosis is made by genetic (DNA) testing showing the presence of the mutation C282Y and/or H63D in the HFE gene. The HFE gene is located on the short arm of chromosome 6. How is the disease transmitted? This disease is transmitted by autosomal recessive mode i.e. When two unaffected carriers of the HFE gene mutation become parents, then for each pregnancy:

There is a 1-in-4 (25%) chance that the child will inherit the normal gene from each parent and will be completely free of the gene mutation and will not be affected by Haemochromatosis (figure A). There is a 2-in-4 (50%) chance that the child will inherit both a regular copy and a faulty copy of the HFE gene and will be a carrier of the faulty gene, unaffected by the disease, just like his/her parents (figures B and C). There is a 1-in-4 (25%) chance that the child will inherit the faulty gene from each parent (figure D). Without early diagnosis and monitoring this child will develop symptoms of Haemochromatosis in 85% of cases.

Does it affect One's health to be a carrier of the HFE genetic mutation? Carriers of the HFE gene mutation are mostly unaffected by the disorder Haemochromatosis. Does Haemochromatosis disease affect only males? No. Haemochromatosis disease can affect both males and females. Males however, are affected in larger numbers than the females and are usually diagnosed earlier in life. This occurs probably because females lose blood during menstruation and childbirth or may have a lower intake of iron and this protects them from iron overload. Is it possible to test for the disease or to determine if you are a carrier of the faulty HFE gene? Yes. In the first instance the degree of iron storage levels in the blood (Serum Ferritin) and the level of iron in the blood (Transferrin Saturation Concentration) are determined. If necessary a genetic test may be carried out for the presence of the HFE gene mutations. Why is a person's ancestry relevant to genetics carrier testing? There are different faults (mutations) found in genes. Some faults are specific to particular ethnic groups or geographical regions in the world and are more common among individuals who are of particular ancestries, origin and descent. Hereditary Haemochromatosis is more common in Caucasians .Our staff will need to ask about your origin and find out whether you are of white European ancestry. For whom is testing for HFE relevant? Testing is available for all men and women over the age of 16. However, it is particularly relevant for persons with history of the disease in their family. Early diagnosis of HH in young adults will prevent the disease from developing harmful consequences. How is the testing performed? Blood samples are tested for the degree of iron storage levels in the blood (Serum Ferritin) and the level of iron in the blood (Transferrin Saturation Concentration) and for the presence of the gene mutation HFE C282Y and/or H63D. If I do not have a family history of HH disease is testing still relevant? Yes. Over 95% of people affected by HH have no family history of the disease because the HFE faulty gene is silently passed down through the generations. However, if there is a family history, then the risk is much greater. People who have a known family history of HH should seek further information through genetic counselling. For counselling call (02) 9926 7324 and the NSW Haemochromatosis Support Society's number is (02) 4473 9099.

Contact: PaLMS Laboratory & Community Genetics: Ph:992-68899 Fax:9926-8484 Email:aproos@doh.health.nsw.gov.au

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