Haemochromatosis DNA Testing; C282Y; H63D
The HFE mutation test is primarily used to detect a mutation called C282Y on the HFE gene. The HFE gene is on chromosome 6. We inherit chromosomes and genes from our parents – including the HFE gene. Each cell in the human body (except sperm and eggs) has 46 chromosomes (23 inherited from the mother and 23 from the father). Genes on these chromosomes form the body's blueprint for producing proteins that control body functions. If a person has C282Y mutations in both copies of the HFE gene - one on each of the pairs of chromosomes, they have a high risk of developing haemochromatosis. Two other mutations H63D and S65C are associated with a more moderate risk of developing haemochromatosis. One or both of these mutations may be tested at the same time.
Most cases of haemochromatosis are found in people who have two copies of the C282Y mutation, one on each of the pair of chromosomes. Some cases of haemochromatosis occur in people who have one copy of C282Y and one of either H63D or S65Y. The technical name for this is that they are compound heterozygotes. People who have two copies of the H63D mutation may have a very slightly increased risk of developing haemochromatosis while people who have only one copy of any of these mutations and one normal gene are not at increased risk.
HFE mutation testing is usually ordered to detect haemochromatosis early before the associated iron overload causes permanent tissue damage. Typical patients will be those with repeatedly elevated serum transferrin saturation or serum ferritin. First-degree relatives of people with known haemochromatosis or known high-risk genotype such as C282Y homozygotes or compound heterozygotes such as C282Y/H63D or C282Y/S65C should also be tested even if they have not yet developed abnormalities in their iron related blood tests.
If the person is found to have a high-risk genotype they can be closely monitored over time and started on treatment early. Treatment is to have blood regularly removed because this removes iron from the body and prevents haemochromatosis developing. If they are eligible, they can become regular blood donors; if they are not eligible they they must still have blood withdrawn at regular intervals.
Iron studies, Ferritin
Healthdirect Australia - haemochromatosis
Genetics Home Reference: HFE
Better Health Channel - haemochromatosis
Mayo Clinic - haemochromatosis (USA)
NSW Government Centre for Genetics Education – Hereditary haemochromatosis (pdf)
Source reference list
Centre for Genetics Education http://www.genetics.edu.au/Publications-and-Resources/Genetics-Fact-Sheets/FactSheet36HereditaryHaemochromatosis.pdf
Haemochromatosis Australia. http://haemochromatosis.org.au/genetics/
OMIM, HFE. http://www.omim.org/entry/613609
OMIM, haemochromatosis. http://www.omim.org/entry/235200
Am Fam Physician. 2013 Feb 1;87(3):183-90. Hereditary hemochromatosis. Crownover BK, Covey CJ.
Gene. 2015 Dec 15;574(2):179-92. doi: 10.1016/j.gene.2015.10.009. Epub 2015 Oct 9. HFE gene: Structure, function, mutations, and associated iron abnormalities. Barton JC, Edwards CQ, Acton RT.
Gastroenterology. 2015 Oct;149(5):1240-1251.e4. doi: 10.1053/j.gastro.2015.06.045. Epub 2015 Jul 9. Genetics, Genetic Testing, and Management of Hemochromatosis: 15 Years Since Hepcidin. Pietrangelo A.
Hematol Oncol Clin North Am. 2014 Aug;28(4):625-35, v. doi: 10.1016/j.hoc.2014.04.006. Epub 2014 Jun 2. Diagnostic evaluation of hereditary hemochromatosis (HFE and non-HFE). Bardou-Jacquet E, Brissot P.
Pathology. 2012 Feb;44(2):148-52. doi: 10.1097/PAT.0b013e32834e8453. Screening for hereditary haemochromatosis. Nadakkavukaran IM, Gan EK, Olynyk JK.
Semin Liver Dis. 2011 Aug;31(3):293-301. doi: 10.1055/s-0031-1286060. Epub 2011 Sep 7. Natural history and management of HFE-hemochromatosis. Gan EK, Powell LW, Olynyk JK.
Last Review Date: February 10, 2020