What is the recommended screening protocol for individuals with a family history of hemochromatosis?

From the Guidelines

Individuals with a family history of hemochromatosis should undergo screening with transferrin saturation and serum ferritin tests, ideally before age 30, as recommended by the American College of Physicians 1.

Key Considerations

• If a first-degree relative has hemochromatosis, genetic testing for the HFE gene mutations (particularly C282Y and H63D) is recommended 1.
• Those who test positive for mutations should have iron studies annually, including transferrin saturation and serum ferritin 1.
• If iron levels are elevated, further evaluation with liver function tests and possibly liver biopsy may be needed to assess organ damage 1.
• Early screening is crucial because hemochromatosis causes progressive iron accumulation that can damage organs silently for years before symptoms appear 1.
• Treatment, which involves regular phlebotomy to remove excess iron, is most effective when started before organ damage occurs 1.

Important Factors

• Siblings of affected individuals have a 25% chance of inheriting the condition if both parents are carriers, making family screening particularly important 1.
• Regular monitoring should continue throughout life for those with genetic mutations, even if initial iron studies are normal 1.
• The USPSTF concludes that the potential harms of genetic screening for hereditary hemochromatosis outweigh the potential benefits, but this does not apply to individuals with a family history of the disease 1.
• Clinically recognized hereditary hemochromatosis is primarily associated with the HFE mutation C282Y, with great racial and ethnic variations in frequency 1.

From the Research

Hemochromatosis Screening Protocol

The recommended screening protocol for individuals with a family history of hemochromatosis involves the following steps:

• Testing should be performed in first-degree relatives of patients with classical HFE-related hemochromatosis, those with evidence of active liver disease, and patients with abnormal iron study results 2
• Serum ferritin measurement is the most useful prognostic indicator of disease severity 2
• Transferrin saturation and serum ferritin level can be used to identify early disease, but the diagnostic usefulness of these tests varies with respect to case definition 3
• Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease 4

Screening Tests

The following screening tests can be used to diagnose hereditary hemochromatosis:

• Serum ferritin level: a level less than 1000 microg/L is predictive of absence of cirrhosis 3
• Transferrin saturation: can be used to identify early disease, but the diagnostic usefulness of this test varies with respect to case definition 3
• Genetic testing for the HFE mutation: can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease 4

Risk Factors

The following individuals are at increased risk of developing hereditary hemochromatosis:

• First-degree relatives of patients with classical HFE-related hemochromatosis 2
• Individuals with evidence of active liver disease 2
• Patients with abnormal iron study results 2
• Men: have a 24-fold increased rate of iron-overload disease compared with women 2
• Individuals with mutations in the HFE gene: may have increased serum iron, transferrin saturation, and ferritin concentrations relative to individuals with the wild-type genotype 5