Hemochromatosis--Genetic Prevalence and Penetrance

This study has been completed.
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
First received: September 28, 2000
Last updated: June 23, 2005
Last verified: March 2005
To examine the cost effectiveness of hereditary hemochromatosis (HH) screening in primary care.

Blood Disease

Study Type: Observational
Study Design: Observational Model: Natural History
Time Perspective: Cross-Sectional

Resource links provided by NLM:

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: July 1999
Estimated Study Completion Date: May 2003
Detailed Description:


Hereditary hemochromatosis (HH) is the most common inherited disorder among Caucasians with an estimated frequency as high as 8 per 1000. Affected individuals absorb excessive amounts of dietary iron and develop progressive accumulation of tissue iron stores with consequent organ dysfunction including hepatic cirrhosis, diabetes mellitus, congestive heart failure, arthropathy and impotence. Early diagnosis and institution of phlebotomy treatments will prevent disease manifestations and normalize life expectancy. In 1996, HFE, the gene for HHC was mapped on the short arm of chromosome 6 (6p21.3). HH is therefore a natural target for the development of a routine screening strategy.


The investigators have demonstrated the favorable cost-effectiveness ratio of adopting a screening strategy for HH and have screened 16,031 primary care patients using serum transferrin saturation (TS) levels to confirm the prevalence of undiagnosed HH in this setting and to demonstrate the feasibility of screening. The recent description of HFE gene mutations in individuals with HH has made genetic testing for HH possible and may increase the attractiveness of general screening. However, several important questions about genetic prevalence and penetrance remain to be addressed before such a recommendation can be made. The large screened sample provides a unique opportunity to address several of these important issues. First, they will obtain population-based estimates of the prevalence of HFE gene mutations. Second, they will determine the sensitivity of serum TS testing for detecting these mutations. Third, the comparison of genotype and phenotype will allow them to draw useful inferences about disease penetrance. The results will enable them to propose an optimal screening strategy for HH and to determine the place of genetic testing in the diagnostic algorithm. This strategy may vary depending on age, sex and race. The answers to these questions will enable them to determine with greater confidence the relative effectiveness of a screening strategy for HH and will clarify for primary care practitioners which of their patients should be screened for this disorder. These questions have recently been identified as a priority by the Centers for Disease Control and Prevention and by the National Heart, Lung, and Blood Institute.


Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
No eligibility criteria
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00006312

Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigator: Pradyumna Phatak University of Rochester
  More Information

ClinicalTrials.gov Identifier: NCT00006312     History of Changes
Other Study ID Numbers: 920
Study First Received: September 28, 2000
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Hematologic Diseases
Genetic Diseases, Inborn
Iron Metabolism Disorders
Iron Overload
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on November 30, 2015