Genes contain the information the body needs to develop from the first cells to the grown adult body. There are about 25,000 to 30,000 genes in the body and research continues to map these genes and understand how they affect our health and well-being. Genes come in pairs that are formed with one from the father and one from the mother.
Inherited disorders are caused by specific genes that have changed, or mutated over centuries and have been passed down through generations. You have no choice in the genes you inherit.
The gene that controls haemochromatosis (inherited iron overload disorder) has been identified and is known as HFE.
While several different mutations to this gene have been discovered, there are two main mutations or faults that cause hereditary haemochromatosis. These are referred to as C282Y and H63D. The C282Y mutation is associated with most cases of hereditary haemochromatosis. The H63D mutation seems to have less impact as do the other much rarer types.
Autosomal Recessive Disorder
Haemochromatosis is a recessive gene disorder. That means for the condition to be passed on, both mother and father must have one copy of the abnormal HFE gene. About one in seven people have one abnormal HFE gene. They are referred to as a ‘carrier’ because they carry a gene which may cause their children to inherit the disorder. Carriers won’t develop the condition themselves.
If two carriers have children, their child has:
• a 50 per cent chance of inheriting one mutated HFE gene and becoming a carrier
• a 25 per cent chance of inheriting both mutated HFE genes and therefore being at risk of excess iron absorption and developing symptoms of haemochromatosis
• a 25 per cent chance of inheriting two normal genes.
Risk of Iron Overload
|Genetic test result||Explanation||Risk of iron overload||How many Caucasian Australians have this genotype?|
|Homozygous C282Y||2 copies of the C282Y mutation||Greatly increased risk||1 in 200|
|Compound heterozygous C282Y / H63D||1 copy of C282Y mutation and 1 copy of H63D mutation||Increased risk||1 in 50|
|Homozygous H63D||2 copies of H63D mutation||Very slightly increased risk||1 in 100|
|Heterozygous H63D||1 copy of H63D mutation and one normal gene||Probably no increased risk||1 in 5|
|Heterozygous C282Y||1 copy of C282Y mutation and one normal gene||Probably no increased risk||1 in 9|
|Normal genotype||No mutations detected||No increased risk||2 in 3|
For a more detailed explanation of the the possible genetic test results, see our Information Sheet 1: Genetic test results and haemochromatosis Mutations: What is your genotype?
Having one copy of the abnormal HFE gene, for example C282Y or H63D – also known as a ‘carrier’.
Two copies of the same gene abnormality, for example C282Y and C282Y.
Having one C282Y and one H63D abnormal gene. Compound heterozygotes usually have a milder form of haemochromatosis.
How does this affect my family?
It is important that family members know if they are at risk of developing iron overload. They can understand their level of risk by having the genetic test performed – this is a simple blood test. Knowing if they have the relevant genes will give them the chance to take control of their condition, and if the gene test shows they are not at risk they will be reassured they have no need to worry.
It can be difficult to talk about these things and sometimes family members are reluctant to listen. Haemochromatosis Australia, with the assistance of our GP Liaison Officer Dr Katie Goot MBBS FACRRM has developed a one page letter suitable to email or post to relatives. It explains what they need to know in simple terms and is even suitable for them to take to their own GP to discuss testing.
Download the letter here.
1 in 700 people with haemochromatosis have no mutation in the HFE gene. This is known as Non-HFE haemochromatosis and is due to mutations in other genes.
Read about the treatment of haemochromatosis here.
Reviewed 3 February 2021.