Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 Jun 1:6:24.
doi: 10.1186/1471-2350-6-24.

Impact of HFE genetic testing on clinical presentation of hereditary hemochromatosis: new epidemiological data

Virginie Scotet  1 , Gérald Le Gac, Marie-Christine Mérour, Anne-Yvonne Mercier, Brigitte Chanu, Chandran Ka, Catherine Mura, Jean-Baptiste Nousbaum, Claude Férec
Affiliations

Impact of HFE genetic testing on clinical presentation of hereditary hemochromatosis: new epidemiological data

Virginie Scotet et al. BMC Med Genet. .

Abstract

Background: Hereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism in Northern European populations. The discovery of a candidate gene in 1996 (HFE), and of its main mutation (C282Y), has radically altered the way to diagnose this disease. The aim of this study was to assess the impact of the HFE gene discovery on the clinical presentation and epidemiology of HH.

Methods: We studied our cohort of 415 patients homozygous for the C282Y allele and included in a phlebotomy program in a blood centre in western Brittany, France.

Results: In this cohort, 56.9% of the patients were male and 21.9% began their phlebotomy program before the implementation of the genetic test. A significant decrease in the sex ratio was noticed following implementation of this DNA test, from 3.79 to 1.03 (p < 10(-5)), meaning that the proportion of diagnosed females relatives to males greatly increased. The profile of HH patients at diagnosis changed after the DNA test became available. Serum ferritin and iron values were lower and there was a reduced frequency of clinical signs displayed at diagnosis, particularly skin pigmentation (20.1 vs. 40.4%, OR = 0.37, p < 0.001) and hepatomegaly (11.0 vs. 22.7%, OR = 0.42, p = 0.006). In contrast, fatigue became a more common symptom at diagnosis (68.0 vs. 51.2%, OR = 2.03, p = 0.004).

Conclusion: This study highlights the importance of the HFE gene discovery, which has simplified the diagnosis of HH and modified its clinical presentation and epidemiology. This study precisely measures these changes. Enhanced diagnosis of HFE-related HH at an early stage and implementation of phlebotomy treatment are anticipated to maintain normal life expectancy for these patients.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Evolution of the sex ratio: number of males and females diagnosed before and after the implementation of the genetic test.
Figure 2
Figure 2
(A) Frequency of the main clinical signs and symptoms at the time of diagnosis in males, before and after the implementation of the genetic test. (B) Frequency of the main clinical signs and symptoms at the time of diagnosis in females, before and after the implementation of the genetic test
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bomford A. Genetics of haemochromatosis. Lancet. 2002;360:1673–1681. doi: 10.1016/S0140-6736(02)11607-2. - DOI - PubMed
    1. Nicolas G, Viatte L, Lou DQ, Bennoun M, Beaumont C, Kahn A, Andrews NC, Vaulont S. Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. Nat Genet. 2003;34:97–101. doi: 10.1038/ng1150. - DOI - PubMed
    1. Muckenthaler M, Roy CN, Custodio AO, Minana B, deGraaf J, Montross LK, Andrews NC, Hentze MW. Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat Genet. 2003;34:102–107. doi: 10.1038/ng1152. - DOI - PubMed
    1. Bridle KR, Frazer DM, Wilkins SJ, Dixon JL, Purdie DM, Crawford DH, Subramaniam VN, Powell LW, Anderson GJ, Ramm GA. Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis. Lancet. 2003;361:669–673. doi: 10.1016/S0140-6736(03)12602-5. - DOI - PubMed
    1. Camaschella C, Roetto A, Cali A, De Gobbi M, Garozzo G, Carella M, Majorano N, Totaro A, Gasparini P. The gene TfR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet. 2000;25:14–15. doi: 10.1038/75534. - DOI - PubMed

Publication types

MeSH terms