Screening for hereditary hemochromatosis
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Bruce R Bacon, MD
Bruce R Bacon, MD
- Professor of Internal Medicine
- Saint Louis University School of Medicine
Hereditary hemochromatosis (HH), also called genetic hemochromatosis, is an inherited disorder in which mutations in the HFE gene or other genes (eg, hemojuvelin, hepcidin, ferroportin, transferrin receptor-2) (table 1) cause a life-long increase in intestinal iron absorption, ultimately resulting in some patients in systemic iron overload and end-organ damage, especially in the liver, heart, and endocrine organs.
While HH in a symptomatic patient may be far advanced, screening of first-degree family members or normal populations may allow diagnosis at an early stage, before irreversible organ damage has occurred. While there is general agreement that first-degree relatives of patients with HH should be screened for the disease, population screening for HH remains a topic of debate [1-3]. The pros and cons of both of these approaches will be reviewed here.
The genetics, pathophysiology, clinical manifestations, diagnosis, and treatment of HH are discussed separately. (See "Genetics of hereditary hemochromatosis" and "Clinical manifestations and diagnosis of hereditary hemochromatosis" and "Approach to the patient with suspected iron overload" and "Management of patients with hereditary hemochromatosis".)
OVERVIEW OF DISEASE PREVENTION AND SCREENING FOR HH
Screening is an important component of preventive care. It consists of the identification of an asymptomatic disease, harmful condition, or risk factor, with the overall aim that the condition be caught early before it causes harm to the affected individual. Since hereditary hemochromatosis (HH) is present at birth, its cause cannot be removed, and primary prevention is not practical. However, secondary prevention, which aims to detect early disease when it is asymptomatic and when treatment might stop it from progressing, is a viable option. (See "Evidence-based approach to prevention", section on 'Preventive activities in clinical settings'.)
Disease penetrance — Disease penetrance is an important issue when family and population screening for HH are performed, as a significant percent of subjects found to have homozygous HH at the time of screening have no evidence for iron overload either at the time of screening [1,4] or after 12 or more years of follow-up [5-8].
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- OVERVIEW OF DISEASE PREVENTION AND SCREENING FOR HH
- Disease penetrance
- Cutoff levels for screening purposes
- - AASLD screening guidelines
- Benefits of screening
- Risks of screening
- DETECTION IN FAMILY MEMBERS
- Screening strategies
- - AASLD consensus guideline for family screening
- Recommended procedure for family screening for HH
- Interpretation of the results of screening
- - Results of genetic testing
- - Results of iron studies
- POPULATION SCREENING
- Studies not favoring population screening
- Studies favoring population screening
- Consensus guidelines for population screening
- Procedures for population screening
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS