Genetic haemochromatosis (also known as "GH") is a condition where a person absorbs too much iron from the diet (they are said to "load iron"). The body cannot naturally get rid of the extra iron - other than through menstruation in women.  The extra iron is stored in the organs and soft tissues - this is haemochromatosis, or "iron overload".

Haemochromatosis can be caused by a number of things, but when it occurs in people with certain gene mutations, it is called genetic haemochromatosis (sometime referred to as "HH" - Hereditary Haemochromatosis). There are several genes that when mutated may cause iron overload and by far the most common in the UK is the "HFE" gene.

Not everyone with the gene mutations involved in genetic haemochromatosis will load iron or have damage to their bodies.  People who have the genes but do not load iron are said to be "predisposed" to genetic haemochromatosis, rather than actually having genetic haemochromatosis.  They may never go on to load iron but continue to be at risk. It is important, therefore, that their iron levels are regularly monitored.

People who have the genes, and who load iron, might not experience symptoms or damage to their bodies.  The human body can cope well with some extra iron.  Damage usually only occurs when there is a large amount of stored iron and it takes many years for this to build up.  However, people who do not experience any symptoms could be loading iron at damaging levels.  It is important that everyone who is loading iron receives treatment to reduce the iron stored in their body.

Having genetic haemochromatosis means… 

…you have two copies of specific HFE gene mutations

(one from each parent)

 AND

 ...you are loading iron

Why it’s important

Iron is important for good health, for example, in producing new red blood cells and muscle development.  Adults absorb about 1mg of iron per day from a healthy diet.  People with genetic haemochromatosis absorb between 2mg and 4 mg per day. When iron is stored in large amounts it is harmful to organs, especially the liver, and other tissues.

Which genes?

The vast majority of people with genetic haemochromatosis have a mutation in the HFE (high iron) gene.  Two particular mutations in that gene, C282Y and H63D, are most commonly involved in genetic haemochromatosis.  In order to have GH, a person must have inherited a mutated gene from both biological parents.

Most people with genetic haemochromatosis have two copies of C282Y – one from each parent (C282Y homozygous). 

Others have a C282Y gene from one parent and a H63D from the other parent (C282Y/H63D compound heterozygous). It is rare for people who are compound heterozygous to load iron in amounts that cause organ damage.

People with two copies of H63D, one from each parent, are considered to have a very low risk of having genetic haemochromatosis.

There are other variants of genetic haemochromatosis that involve other genes; these are exceptionally rare.

Are there stages of the condition?

Yes. There are three main stages of genetic haemochromatosis :

• Predisposition - having the HFE gene mutations without iron overload
• Iron overload without evidence of organ damage
• Iron overload with organ damage

The most severe cases of genetic haemochromatosis involve organ failure.

Will everyone go through all of these stages?

No. If diagnosed and treated early, later stages can be avoided.

How much iron is normal?

Two tests are used to assess the amount of iron in the body.  These are called Serum Ferritin (SF) and Transferrin Saturation (TS).

The normal range for men is:

• Serum Ferritin (SF) 15-300µg/l
• Transferrin Saturation (TS or TSat) 16-50%

The normal range for women is:

• Serum Ferritin (SF) 15-200µg/l
• Transferrin Saturation (TS) 16-45%

µg/l means micrograms per litre – a definition of concentration of the amount of iron.

Variation in transferrin saturation levels is not always due to iron overload and some doctors recommend a fasting test which may be more reliable.

How common is genetic haemochromatosis?

Genetic haemochromatosis is the most common genetic condition in people of Northern European ancestry – about one in 150 people are affected[1].  Among people with Celtic ancestry, the condition is even more common.

Does it affect women and men equally?

Men are more likely than women to develop organ damage from genetic haemochromatosis.  It takes many years for iron to build up to damaging levels in the body.  Women lose iron during menstruation which can help to protect them from iron overload during their reproductive years.  In the UK, about one in every four men who are C282Y homozygous are diagnosed with problems linked with iron overload by the time they reach their seventies. About half as many women who are C282Y homozygous in their seventies have organ damage linked to genetic haemochromatosis[1].

We don’t yet know why many people with the gene mutations do not develop problems linked with iron overload. This will be an important avenue for research.

 

Clinical Advisory Panel

Haemochromatosis UK

4 December 2019

[1] "Hereditary Haemochromatosis - Estimates of Excess Disease In The UK" (July 2019) - Professor David Melzer & the Exeter Haemochromatosis research group, University of Exeter