Family-based Detection
Genetic Testing & Basic Counseling
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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 mutations |
Chance of family member having two
C282Y mutations |
|
None (general population)
|
1 in 400 (~0.26%) |
|
Brother or sister |
1 in 4 (~25.0%) |
|
Parent |
1 in 20 (~5.0%) |
|
Child |
1 in 20 (~5.0%) |
|
Niece or nephew |
1 in 80–160 (~1%) |
|
(Adams PC, 2001) |
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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.
This table provides basic counseling points to consider for patients with
different combinations of genotypes and iron study results:
| Genotype |
Iron study |
Counseling points to consider |
|
C282Y/C282Y
|
Indicate iron overload |
A patient who has symptoms has hereditary hemochromatosis –
begin treatment.
Screen family members – transferrin saturation test. |
|
C282Y/C282Y |
Normal |
Patient 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/normal |
Normal |
Patient 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/H63D |
Indicate iron overload |
A patient who has symptoms has hereditary hemochromatosis –
begin treatment.
Screen family members – transferrin saturation test. |
|
C282Y/H63D |
Normal |
Patient may be at slightly increased risk (<1%) of developing
hemochromatosis
Monitor iron status every 2–5 years.
Screen family members – transferrin saturation test |
|
H63D/H63D |
Normal |
Patient may have slightly (<1%) increased risk of developing
hemochromatosis.
Monitor iron status every 2–5 years. |
|
H63D/normal |
Normal |
Patient 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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