C282Y Homozygous This is the most common variant of the condition in the UK, affecting 9 in every 10 people diagnosed. People with this variation tend to load iron much more quickly compared to other people with genetic haemochromatosis (GH). The condition can cause iron overload, due to a genetic change in the HFE gene, which affects the operation of hepcidin, a protein which helps to regulate iron in the body. Implications for people with this genetic variant Individuals who are homozygous for this mutation are considered at risk of developing iron overload. However, not everyone develops symptoms or develops ill-health from this genetic pre-disposition. Iron levels are assessed through a simple blood test for serum ferritin and transferrin saturation. A GP can arrange these tests. Too much iron is known as “iron overload”. A C282y homozygote result combined with the presence of iron overload is consistent with a clinical diagnosis of Genetic Haemochromatosis. If you have iron overload you should be referred to a hospital for treatment, depending on your specific circumstances. Treatment is a form of regular blood donation, known as venesection. Everyone is different – some people load iron rapidly and others less quickly. Your venesection schedule will be adjusted to your specific circumstances. Typically people with iron overload are venesected every week or every fortnight for an initial period of weeks or months, to bring iron levels down to normal. Once iron levels approach normal levels, the venesections continue, but less often – usually every 3-12 months. The aim is to keep iron levels at normal levels. If following a genetic test you presently have normal serum ferritin and transferrin saturation levels it is recommended that you have transferrin saturation and serum ferritin checked every year. These tests can be organised by your General Practitioner or through Haemochromatosis UK. Women who have regular menstruation (with consequent regular blood loss) are less likely to develop iron overload, however once periods stop through contraceptive use or early menopause, a gradual rise in iron may occur. Family members If you have a confirmed genetic test for C282y homozygosity, your first-degree relatives should also be tested. Family screening should include parents, siblings, partner and children over 18 years old. Laboratory testing would include Full Blood Count (FBC), Liver Function Tests (LFTs), Serum Ferritin (SF), Transferrin Saturations (TSAT). Genetic testing (for HFE mutations) should be offered to family members following your diagnosis of C282y homozygosity. There are no immediate implications for babies and younger children under 18 years of age. Their testing can be postponed until they can give informed consent in early adulthood. Any children you have will be carriers for genetic haemochromatosis, with a small chance (approximately 1 in 20, 5%) of them each having genetic haemochromatosis themselves. Your siblings will each be at a 1 in 2 (50%) chance of being carriers with a 1 in 4 (25%) chance of having genetic haemochromatosis themselves. Due to all children of C282y homozygous being carriers, if they wish to start a family it is important to establish the other parent’s genetic status. If their future partners are carriers, then there will be a 1 in 4 chance (25%) of having a genetic predisposition for iron overload in any children they have.