Hereditary hemochromatosis: time for targeted screening

Area of Science:

• Genetics
• Iron Metabolism
• Internal Medicine

Background:

• The discovery of the HFE gene revolutionized understanding of iron absorption and storage.
• Genetic definition of hereditary hemochromatosis (HH) is now possible with widely available HFE mutation testing.
• Population screening studies reveal lower-than-expected disease penetrance for HFE-related HH.

Purpose of the Study:

• To re-emphasize hereditary hemochromatosis as a cause of preventable organ dysfunction.
• To propose targeted case finding strategies for hereditary hemochromatosis.
• To identify specific populations for targeted screening.

Main Methods:

• Review of advances in understanding HFE gene and hereditary hemochromatosis.
• Analysis of population screening study data regarding disease penetrance.
• Evaluation of the effectiveness of early detection and therapy.

Main Results:

• HFE gene discovery enabled genetic definition and testing for hereditary hemochromatosis.
• Disease penetrance for HFE-related HH is lower than previously thought, making universal screening unattractive.
• Hereditary hemochromatosis can cause significant morbidity and mortality due to iron overload if undetected.

Conclusions:

• Early detection and therapy are crucial for preventing iron overload complications in hereditary hemochromatosis.
• Targeted case finding, rather than universal screening, is a more effective strategy.
• Caucasian men of Northern European ancestry are proposed as a target group for case finding.