Genetic Testing for Hereditary Hemochromatosis

Confirming Your Diagnosis

Hereditary hemochromatosis is caused by changes (mutations) to the HFE gene associated with hemochromatosis. The HFE gene is responsible for regulating the amount of iron that is absorbed into the body from the food that we eat. The HFE gene has three known mutations which cause hemochromatosis, namely the C282Y mutation, the H63D mutation and the S65C mutation. The C282Y mutation is the one most commonly found in individuals with hemochromatosis.

Genetic testing (sometimes referred to as DNA testing) for hereditary hemochromatosis examines the HFE gene for mutations that cause the gene to become defective. HFE genetic testing confirms the diagnosis of HFE hemochromatosis in individuals with clinical symptoms consistent with hemochromatosis and/or biochemical evidence of iron overload. Here are some basic facts about HFE genetic testing and what to expect from a genetic test result:

  • HFE genetic testing can be performed on either blood or buccal (mouth) swab samples.
  • Results from DNA testing for the mutations associated with hereditary hemochromatosis will give you an indication of your risk for iron overload and will also provide information about the statistical probability of your children inheriting the risk (see Genetic Inheritance).
  • The absence of mutations associated with hemochromatosis nearly excludes the possibility of hereditary hemochromatosis (excellent negative predictive value).*
  • The penetrance (the likelihood that you will develop clinical iron overload) of the HFE mutations is not 100%. That means that if you test positive for two copies of the defective gene, you are at an increased risk of over-absorbing dietary iron, but it does not mean that you will definitely develop iron overload.
  • The type and number of HFE mutations affects your risk of developing hemochromatosis. For example, an individual with two copies of the C282Y mutation is at more risk for developing hemochromatosis than an individual with only one copy of C282Y and one copy of H63D or S65C.
  • Hemochromatosis is the most common genetic disorder in individuals of Celtic and Northern European ancestry. 1 in 9 Canadians are carriers of at least one of the HFE gene mutations associated with hereditary hemochromatosis.
  • About 87% of individuals of Celtic and Northern European origin who are clinically affected by hereditary hemochromatosis are either homozygotes for the C282Y mutation or compound heterozygotes for the C282Y and H63D mutations.

View a glossary of terms used on this page.

*A small percentage of clinical cases may be caused by yet unidentified mutations in the HFE gene or another gene, which cannot be ruled out by HFE analysis of C282Y, H63D and S65C.