Hemochromatosis--Genetic Prevalence and Penetrance

Blood Disease Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006312
• Other study ID #: 920
• Secondary ID: R01HL061428
• Status: Completed
• Phase: N/A
• First received: September 28, 2000
• Last updated: January 14, 2016
• Start date: July 1999
• Est. completion date: May 2003

Study information

• Verified date: January 2016
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

To examine the cost effectiveness of hereditary hemochromatosis (HH) screening in primary care.

Description:

BACKGROUND:

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.

DESIGN NARRATIVE:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: May 2003
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 100 Years
• Eligibility: No eligibility criteria

Study Design

N/A

Related Conditions & MeSH terms

• Blood Disease
• Hematologic Diseases
• Hemochromatosis

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Rochester	National Heart, Lung, and Blood Institute (NHLBI)

References & Publications (2)

Phatak PD, Ryan DH, Cappuccio J, Oakes D, Braggins C, Provenzano K, Eberly S, Sham RL. Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients. Blood Cells Mol Dis. 2002 Jul-Aug;29(1):41-7. — View Citation

Sham RL, Raubertas RF, Braggins C, Cappuccio J, Gallagher M, Phatak PD. Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles. Blood. 2000 Dec 1;96(12):3707-11. — View Citation