In the UK, when a genetic test is requested to look out for genetic haemochromatosis, the laboratory will analyse the HFE gene to establish if there are any mutations, such C282y, H63d and S65C. It is important to note that there are more mutations within the HFE gene however they had not been shown to have a significant impact on the body’s iron mechanism and for this reason it is not routinely checked. The mutations included on the genetic test panel analysis might vary from country to country. For more info regarding the 3 most common HFE mutations:
The most common type of carriers is linked to HFE mutations (type 1) however it might also be linked to other genetic mutations which causes type 2 (HJV and HAMP genes), type 3 (TFR2 gene) and type 4 (SLC40A1).
Misdiagnosis of compound heterozygous as carriers
At the time of the diagnosis, it is important to have the results 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 is not only a carrier but has got type 1 Genetic Haemochromatosis. In this case, this individual is compound heterozygous.
Family implications for carriers
At least one of your biological parents will be a carrier for genetic haemochromatosis, and there is a small chance (approximately 1 in 40, or 3%) that one of your parents could have genetic haemochromatosis.
Brothers and sisters have a 1 in 4 (25%) chance of being affected only if both parents are carriers.
Each of your siblings and any children you have are at a 1 in 2 (50%) chance of also being a carrier.
There is a small chance (1 in 40 or 3%) to your siblings and children of them having genetic haemochromatosis.
Carrier testing for first degree adult relatives can be considered.
There will be no immediate implication for children under the age of 18 years and babies thus testing is not recommended at this age.
If you are a carrier for the genetic mutations causing type 4 genetic haemochromatosis, then it is guaranteed that your children will inherit that mutation as this form of the condition is inherited in an autosomal dominant manner, which differs from the other types of the condition.
Symptoms
Carriers might be at risk of iron loading. If you have normal iron levels and no symptoms, you will require to have serum ferritin and transferrin saturation levels monitored every 2-3 years.
If you have symptoms and raised serum ferritin and/or transferrin saturation then you may need to be referred to the hospital for further investigations.
In some cases, carriers experience similar symptoms to those diagnosed with C282y homozygous and compound heterozygous when accompanied by other genetic mutations. For this reason, it is important to be referred for further investigations to establish whether this is the case or not.
For more information regarding related symptoms, treatment and care advice:
- What is genetic haemochromatosis, including common symptoms?