Training & Education - Family-based DetectionGenetic Testing and Basic Counseling

Genetic testing in families with HFE-associated hemochromatosis can be particularly useful for determining:

• Who is NOT at increased risk: A family member (blood relative) who has no HFE mutations has the same risk of developing hemochromatosis as the general population.
• Whether iron overloading is genetic: In a hemochromatosis patient, finding two HFE mutations confirms that his or her iron overloading is genetic and is therefore hereditary hemochromatosis.

Genetic testing cannot predict who will develop hemochromatosis.

• Biochemical testing for iron overload (fasting transferrin saturation and serum ferritin) is therefore more clinically relevant than genetic testing for determining which family members have elevated iron measures and need treatment.
• It is important to consider that iron overloading occurs over time. If a family member’s serum iron measures are normal now, he or she should have repeat testing every 2–5 years.

Estimates for the risk of inheriting two C282Y mutations for family members related to a patient with two C282Y mutations (HFE genotype that confers susceptibility to increased iron absorption) are provided in the table:

For example, siblings of an affected person have a 25% chance of having two C282Y mutations. However, not all people with HFE gene mutations will develop hemochromatosis. (Beutler E, 2002; Bulaj ZJ, 2000; Olynyk JK, 1999)

Counseling Patients with Genetic Test Results

While genotyping is an option, insurance discrimination and employment issues should be discussed with the patient before gene tests are performed. Some insurers may misinterpret a demonstration of C282Y/C282Y homozygosity as definite disease, even if iron overloading is not present. Penetrance of H63D mutations for iron loading is quite low.

As a result, genotyping provides less clinically relevant information than do direct iron studies.

Counseling patients about genetic testing and test results is complex and beyond the scope of this website, but basic counseling guidelines are provided in the following table.

Basic Counseling

This table provides basic counseling points to consider for patients with different combinations of genotypes and iron study results:

Patients & Families Summary