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Hereditary Hemochromatosis
  Is Genetic Testing Available?
hemochromatosis genetic testing

By Amanda Ewart Toland, PhD

Reviewed by Chris Friedich, MD, PhD

A suspected clinical diagnosis of hemochromatosis, following laboratory tests such as an elevated transferrin saturation level, is often confirmed by genetic tests for mutations in the HFE gene. These tests can also detect if a person without any symptoms of iron storage disease may be at risk for developing symptomatic hemochromotosis. For individuals with hereditary hemochromatosis, further laboratory tests including liver biopsies may determine how far the order has progressed.


Nongenetic (Standard) Laboratory Tests for Hemochromatosis

Genetic testing can identify over 80 percent of people at risk of developing hemochromatosis symptoms. But other blood tests can also indicate when someone may be at risk for developing symptoms. These tests can also detect iron overload from causes other than hemochromatosis, as well as iron deficiency.

The medical community is still debating whether everybody should be screened for hemochromatosis.
hemochromatosis genetic testing

The recommendations for traditional (or biochemical) hemochromatosis screening vary. The medical community is still debating whether everybody should be screened for hemochromatosis, or if screening should be confined to individuals known to be at risk. As researchers and clinicians learn more about the impact of hemochromatosis screening on general healthcare, recommendations will become more standardized. The College of American Pathologists recommends that everyone over 18 have iron storage tests as part of routine medical care. However, the National Institutes of Health and the Center for Disease Control both recommend screening only in individuals with symptoms of hemochromatosis, or a family history of the disease.

More on Nongenetic Testing for Hemochromatosis (Coming Soon)
hemochromatosis genetic test

Who Might Benefit From Genetic Testing?

Genetic testing is often recommended to confirm a hemochromatosis diagnosis in people with increased iron storage levels. Adult relatives of patients with hemochromatosis may also be diagnosed early by DNA testing, even before iron levels begin to increase.

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How Is Genetic Testing Done?

Genetic testing for hemochromatosis determines whether a specific mutation is present or absent in a DNA sample.
hemachromatosis gene test
Genetic testing for hemochromatosis involves a simple blood test. DNA from the blood is extracted and the HFE gene is tested for two specific mutations in the gene known to cause the disease in most people. There are two laboratory techniques typically used to detect the two mutations: allele-specific oligonucleotide hybridization (ASO) and restriction fragment length polymorphism (RFLP) analyses. Both of these tests are designed to detect whether a specific mutation is present or absent in a DNA sample. These tests will also determine if an individual is a carrier of either mutation.

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What Does the Genetic Test Measure?

The two mutations typically tested for are most commonly called C282Y and H63D. The mutations are named based on their location within the HFE gene and the change that they cause in the gene's instructions. The two mutations differ in how frequently they are found in the population, and in how severe your hemochromatosis is if you have them. There are other rare mutations that may predispose individuals towards abnormal iron storage. However they are not yet part of most laboratories testing panels for hemochromatosis.

Current estimates are that 87 percent of people with hereditary hemochromatosis will be identified if genetic testing is done for the C282Y and H63D mutations of the HFE gene.


What if the Test Is Negative?

hemachromatosis gene testing
A liver biopsy is used to rule out other disorders that can cause elevated iron storage levels.
hemochromatosis genetics
Liver biopsies, in which a tiny piece of liver tissue is removed and examined under a microscope, are often recommended for individuals who have a negative genetic test combined with a diagnosis of hemochromatosis by clinical symptoms and increased iron storage levels (serum transferrin saturation levels above 65 percent). The liver biopsy is used to rule out other disorders that can cause elevated iron storage levels, such as porphyria cutanea tarda, thalassemia, or other chronic anemias requiring multiple transfusions, viral hepatitis, alcoholic liver disease, and other forms of secondary iron overload. If these disorders are ruled out, it may mean that you have one of the rare mutations that cause hemochromatosis, for which tests are not currently available.



False Positive Test Results

A small subset of people (less than four percent) who are tested for hereditary hemochromatosis based on a family history, may have a normal variant in their HFE gene that gives a false positive test result. Many genetic testing laboratories are aware of this variant and have adjusted their testing procedures. Any person with a positive genetic test for the C282Y mutation in both copies of the HFE gene and the absence of any increased iron storage by other laboratory measures should have their doctor ask the laboratory about this normal variant. In young adults with an affected brother or sister, the most likely explanation for this result is that they have the genes for hemochromatosis but have not yet accumulated large amounts of iron. But this alternate explanation should be ruled out.




Risch, N. (1995). Haemochromatosis, HFE and genetic complexity.Nature Genetics 17: 375-376.

Adams, P. C. (1999). Population Screening for Hemochromatosis. Hepatology. 29:1324-1327.

Cogswell, M.E. et al. (1999). Screening for hemochromatosis: a public health perspective. Am. J. Prev. Med. 16: 134-139.

GeneClinics website. (2000). http://www.geneclinics.org

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