Screening for HFE and Iron Overload
Type 1 hereditary hemochromatosis is a common disorder of iron overload occurring in individuals homozygous for the C282Y HFE gene mutation. It can be a progressive and fatal condition. Early detection and phlebotomy prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with clinical features suggestive of iron loading. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified. Potential ethical, legal, and psychosocial issues arising through application of genetic screening programs also must be resolved prior to implementation of general population screening programs.
Type 1 hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron overload which is most commonly due to a homozygous C282Y mutation within the HFE gene on chromosome 6. HFE gene mutations are common and can lead to irreversible organ damage with complications of cirrhosis, diabetes, and arthritis. Thus, it is critical that affected subjects be diagnosed during the early asymptomatic phase of the disorder. Therefore, first-degree relatives of known C282Y homozygotes should be screened routinely so that treatment can be instituted to prevent organ damage. Population-based screening has been proposed as a means to decrease HH-associated morbidity and mortality at a community level, largely because the disorder is relatively common and easily diagnosed and treated. However, population-based screening remains controversial due to several concerns including the variable phenotypic expression of the disease, the issue of phenotypic versus genotypic screening, and overall cost-effectiveness. In this article, we review the prevalence of mutations in the HFE gene and address screening for HH in families, the general population, and particular clinical scenarios where patients may be at higher risk of having HH.
Type 1 hereditary hemochromatosis is a common disorder of iron overload occurring in individuals homozygous for the C282Y HFE gene mutation. It can be a progressive and fatal condition. Early detection and phlebotomy prior to the onset of cirrhosis can reduce morbidity and normalize life expectancy. It is readily identified through biochemical testing for iron overload using serum transferrin saturation and genetic testing for C282Y homozygosity. General population screening has been waived in preference to targeting high-risk groups such as first-degree relatives of affected individuals and those with clinical features suggestive of iron loading. This screening strategy is likely to continue until uncertainties regarding the natural history of the disease, age-related penetrance, and management of asymptomatic individuals are clarified. Potential ethical, legal, and psychosocial issues arising through application of genetic screening programs also must be resolved prior to implementation of general population screening programs.
Type 1 hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron overload which is most commonly due to a homozygous C282Y mutation within the HFE gene on chromosome 6. HFE gene mutations are common and can lead to irreversible organ damage with complications of cirrhosis, diabetes, and arthritis. Thus, it is critical that affected subjects be diagnosed during the early asymptomatic phase of the disorder. Therefore, first-degree relatives of known C282Y homozygotes should be screened routinely so that treatment can be instituted to prevent organ damage. Population-based screening has been proposed as a means to decrease HH-associated morbidity and mortality at a community level, largely because the disorder is relatively common and easily diagnosed and treated. However, population-based screening remains controversial due to several concerns including the variable phenotypic expression of the disease, the issue of phenotypic versus genotypic screening, and overall cost-effectiveness. In this article, we review the prevalence of mutations in the HFE gene and address screening for HH in families, the general population, and particular clinical scenarios where patients may be at higher risk of having HH.
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