Genetics

GH is caused by the inheritance of two mutated copies of the HFE gene (meaning high ferritin) leading to increased iron absorption across the intestinal mucosa. GH is an autosomal recessive condition, which means two copies of a variant (mutated) gene must be present for haemochromatosis to develop. There are three known variants of the HFE gene, classified from where they are located on the gene; C282Y, H63D and S65C (rare).

Watch this video to learn about the genetics of haemochromatosis (5 minutes) :

Patients with a single copy of either C282Y or H63D mutations (heterozygotes) are termed carriers. Typically, they do not overload iron. People who have 2 copies of the same mutation are known as homozygotes e.g. C282Y/C282Y. If they have a mixture of 2 genes they are known as compound heterozygotes e.g. C282Y/H63D. Homozygotes are at a higher risk of loading iron. However, not all people who inherit these gene mutations will load iron, or load iron at different rates. This is termed penetrance. This is not fully understood but is thought that there are other factors that contribute to this such as environmental factors or gender.  Research studies are ongoing to identify other gene mutations that may help explain haemochromatosis in patients who do not have these mutations listed above.

There are five types of GH :

Learning points

  • GH is an autosomal recessive condition, which means two copies of a mutated gene must be present (one inherited from each parent) for haemochromatosis to develop
  • People who inherit one copy of either the C282Y or H63D mutations are termed heterozygotes (carriers)
  • People who inherit 2 copies of the same gene are termed homozygotes
  • People who inherit 2 different copies (1 of each) are termed compound heterozygotes
  • GH can be classified into 4 types

Next steps

Symptoms