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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:

Relationship to hemochromatosis patient with two C282Y mutationsChance of family member having two C282Y mutations
None (general population)1 in 400 (~0.26%)
Brother or sister1 in 4 (~25.0%)
Parent1 in 20 (~5.0%)
Child1 in 20 (~5.0%)
Niece or nephew1 in 80–160 (~1%)
(Adams PC, 2001)

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:

GenotypeIron studyCounseling points to consider

C282Y/C282Y

Indicate iron overloadA patient who has symptoms has hereditary hemochromatosis – begin treatment.
Screen family members – transferrin saturation test.
C282Y/C282YNormalPatient has increased risk of developing hemochromatosis.
Monitor iron values every 2–5 years.
Patient may have decreased likelihood of needing iron supplements.
Screen family members – transferrin saturation test.
C282Y/normalNormalPatient is carrier, like 5% of U.S. population.
Family does not require testing. Patient is not likely to develop iron overload and may be protected against iron deficiency.
C282Y/H63DIndicate iron overloadA patient who has symptoms has hereditary hemochromatosis – begin treatment.
Screen family members – transferrin saturation test.
C282Y/H63DNormalPatient may be at slightly increased risk (<1%) of developing hemochromatosis
Monitor iron status every 2–5 years.
Screen family members – transferrin saturation test
H63D/H63DNormalPatient may have slightly (<1%) increased risk of developing hemochromatosis.
Monitor iron status every 2–5 years.
H63D/normalNormalPatient is carrier, like 13.5% of U.S. population.
Family does not require screening.
Patient may be protected against iron deficiency.

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