People who have one gene C282y and one gene H63d are known as “compound heterozygotes”. Our charity recognises that there is a spectrum of opinion within academic and clinical communities on the prevalence and effects of compound heterozygosity. We are also mindful that the charity has many compound heterozygote members who tell us that they experience iron overload and ill-health as a result.

The charity’s position regarding Type 1 compound heterozygosity is long-standing : 

• People who are compound heterozygous (ie C282y/H63d) can load iron .
• People who are compound heterozygous who load iron tend to do so less rapidly than people with other variants of genetic haemochromatosis.
• People who are compound heterozygous can develop symptoms commonly associated with “iron overload”.

Misdiagnosis of compound heterozygous as "just carriers"

We regularly see people who are compound heterozygous being mis-diagnosed as "just a carrier". At the time of the diagnosis, it is important to request the genetic test results and to have them interpreted correctly to avoid misdiagnosis. The nursing team at Haemochromatosis UK is here to help to interpret the results, if you get in touch.

A carrier is when an individual has inherited one single copy of the HFE mutation. If the result shows that the individual has inherited 2 different copies, then that person is not a carrier but has got type 1 Genetic Haemochromatosis. In this case, this individual is compound heterozygous.

Implications for people with this genetic variant

Iron is assessed through a simple blood test for serum ferritin and transferrin saturation. Too much iron is known as “iron overload”.

• This genotype appears to be associated with a small increased chance of developing (usually mild) iron overload. However, this is often associated with other health problems factors such as obesity, non-alcoholic fatty liver disease (NAFLD), excess alcohol consumption and end-stage cirrhosis.
• As this mutation has not been extensively studied there is currently limited evidence to suggest if people develop ill-health from this genetic pre-disposition.
• 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. However, 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 checks every three years. These tests can be organised by your General Practitioner or through Haemochromatosis UK.
• At this time, you could become a blood donor, subject to the normal donor eligibility criteria. For more details of blood donation in your region, visit :  https://www.haemochromatosis.org.uk/can-i-donate-blood.
• 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/H63d, your first-degree relatives should also be tested. Family screening should include parents, siblings, partner and children 18 years and older.
• Brothers and sisters of the patient have a 1 in 4 chance of being affected and should be offered genetic counselling.
• 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.
• All children will be carriers but are only at risk if their other parent is also affected or a carrier.