Find out if you are at risk - get tested
After genetic testing, there are several possible outcomes:
Outcome #1: Normal
If the tested individual does not have any copies of the defective HFE gene, the person is considered normal and not likely to develop hereditary hemocromatosis and will not pass this disease to further generations.
Outcome #2: Carrier
If the tested individual has one defective HFE gene and one normal HFE gene, the person is considered a carrier of hemochromatosis. A carrier usually does not express symptoms of hemochromatosis but has a 50% chance of passing the defective HFE gene to future generations. If two carriers have children, there is a 25% chance that their children will be normal, a 50% chance that their children will be carriers of the disease, and a 25% chance that their children will have two defective HFE genes and be at risk of developing hemochromatosis.
Outcome #3: Affected
If a tested individual has two copies of the defective gene, the person is considered affected and has a significant risk of absorbing too much iron and eventually developing hemochromatosis. The extent of symptoms and disease varies greatly between different people. Some people may never exhibit symptoms of hemochromatosis while others may be critically affected. Affected individuals have a 100% chance of passing the defective HFE gene to the next generation.
A positive test for the defective HFE gene implies that other family members may also be at risk of hemochromatosis and should also be tested. Individuals with one or more than one copy of the defective HFE gene should consider testing their partner prior to having children to determine the risk of having a child that is affected with hemochromatosis.
Significance of Alleles
Individuals who are homozygous for C282Y are at increased risk for developing hereditary hemochromatosis. C282Y is found in the homozygous state in approximately 85% of all individuals who are clinically affected with hereditary hemochromatosis. Iron overload is detected in 90% of males and 50% of females, and 2% will develop characteristic clinical end points (diabetes mellitus, hepatic cirrhosis, cardiomyopathy, etc.). Approximately 30% are asymptomatic. The C282Y mutation is associated with a more penetrant and severe phenotype than H63D and S65C.
Individuals who are homozygous for H63D are only at a slightly increased risk of developing hereditary hemochromatosis. Iron overload is detected in 1% of males and 0.5% of females.
C282Y/H63D Compound Heterozygote
Individuals who are compound hereterozygous for C282Y/H63D are at an increased risk for developing a clinically milder form of hereditary hemochromatosis. This form is found in approximately 3 to 8% of individuals who are clinically affected with hereditary hemochromatosis. Approximately 1% to 2% of individuals with this genotype will develop clinical evidence of iron overload. While individuals with this genotype may have increased iron indices, many do not develop clinical disease without other precipitating factors (hepatitis, alcohol abuse).
C282Y/S65C Compound Heterozygote
Individuals who are compound heterozygous for C282Y and S65C may have a small risk for mild hemochromatosis. This rare variant displays a very low penetrance.
Individuals who are heterozygous for C282Y may have mild symptoms of hemochromatosis such as lethargy, joint pain, and weakness but are unlikely to develop the disease.
Individuals who are heterozygous for H63D are unlikely to have symptoms of iron overload and are not at significantly increased risk of developing the disease.
Note: Individuals who are heterozygous for S65C or compound heterozygous H63D/S65C do not seem to be at a measurably increased risk for hereditary hemochromatosis. Accordingly, the S65C mutation is only reported when it is part of the C282Y/S65C compound heterozygous genotype.
Limitations of the Test
This assay detects the C282Y, H63D, and S65C mutations in the HFE gene to help identify those who are at increased risk for hereditary hemochromatosis.
Increased risk for hemochromatosis can also be caused by a variety of genetic and nongenetic factors not detected by this assay. Although the test detects the most common hemochromatosis gene (HFE) mutations which are found in 85% of individuals with the disease, there may be other yet undiscovered HFE mutations that the test does not detect, so the absence of a detectable mutation(s) does not rule out the possibility that an individual is a carrier of or affected with this disease.
An abnormal test result which confirms that you are affected with two copies of the defective gene indicates that you are at increased risk of developing hereditary hemochromatosis. It does not mean that you will definitely develop hemochromatosis as the range and severity of symptoms experienced by individuals who carry the defective HFE gene varies greatly between different individuals. Test results should be interpreted in the context of clinical findings, family history, and other biochemical and clinical data.
The DNA examines 3 types of mutations in the HFE gene which accounts for approximately 85% of cases of hereditary hemochromatosis. The other 15% of individuals with symptomatic hemochromatosis may have other mutations which have not yet been discovered. Only some of those who test positive will actually develop serious illness.