What is Genetic Haemochromatosis
Explaining genetic haemochromatosis and iron overload
What is Genetic Haemochromatosis (GH)
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Haemochromatosis is the medical term for excess iron in the body - otherwise called iron overload. Excess iron is extremely toxic and can affect many parts of the body.
At the charity we describe Genetic haemochromatosis (GH) as having the underlying genetics that puts someone at greater risk of developing haemochromatosis, or iron overload. Having the genetics does not mean you will go on to have iron overload - especially if the genetic diagnosis is made early.
Iron overload affects everyone differently. Many people experience one or more symptoms., but some people don't experience any noticeable symptoms.
Symptoms of genetic haemochromatosis can include the following:
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Arthritis; may affect any joint but particularly common in the knuckle and first joint of the first two fingers (the bronze fist). If arthritis is found only in the first two finger joints this is highly suggestive of GH
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Chronic fatigue, weakness, lethargy
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Abdominal pain; sometimes in the stomach region or the upper right hand side, sometimes diffuse
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Neurological/psychiatric disorders; impaired memory, mood swings, irritability, depression
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Sexual disorders; loss of sex drive, impotence in men
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Absent or scanty menstrual periods and early menopause in women
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Bronzing of the skin, or a permanent tan, or grey tone
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Cardiomyopathy; disease of the heart muscle
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Diabetes (late onset type)
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Pituitary or adrenal issues (eg Addison's Disease)
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Liver disorders; abnormal liver function, enlarged liver, cirrhosis, liver cancer
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Sepsis/bacterial infections : people with some types of genetic haemochromatosis are at significantly increased risk of sepsis and bacterial infections
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Decrease in body hair
Most of these symptoms are found in other disorders. For example chronic fatigue may be ascribed to after-effects of a viral infection or to psychological causes, and abdominal pain to irritable bowel syndrome. Similarly liver disorders may be put down to excessive alcohol intake, even in someone who is only a moderate drinker. However, if some of the symptoms listed above are present, GH should be considered as a diagnosis.
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Individuals who have GH can, if untreated, develop at least one or two of the above symptoms, although possibly only in a very mild form. There may be a long phase of the condition where there are no symptoms.
Fatigue, liver and joint problems are ‘typical’ symptoms developing (though this does vary of course). Joints complaints are typical of the elderly and sexual problems typical of younger people at diagnosis.
The need for treatment to remove excess iron does not depend upon the presence of clinical symptoms. The risk of developing a serious complaint such as cirrhosis is much too great to be overlooked.
More Info on Type 1 GH
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HFE (Type 1) Genetic Haemochromatosis
Inherited (genetic) disorders are caused by defective genes in the cells which make up the body.
Genes are made of DNA and contain the information the body needs to develop from the egg and to maintain itself in good working order. We have about 30,000 genes and every cell in the body, except sperm and egg cells, contains two copies of each. One of these copies is inherited from our mother and one from our father. In 1996 the HFE gene was identified as the major gene implicated in haemochromatosis.
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We have also produced a detailed guide to genetic haemochromatosis. This guide is included in our membership pack alongside lots of other information. When you join - this Welcome Pack is sent to you in the post.
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The genetics of GH
A small change (mutation) is present in both copies of the gene in over 90% of those diagnosed with GH. GH is an autosomal recessive disorder, which means that the risk of absorbing excess iron is higher if both copies of the gene are abnormal.
Someone with only one copy of a mutation rather than two is said to be a carrier. If only one copy is defective, an individual will usually be unaffected, but it is known that carriers. Some carriers are known to load iron, sometimes. A carrier is able to pass on his or her abnormal copy of the gene to a son or daughter.
Sperm and egg cells have only one copy of each gene, and on average half the eggs or half the sperm of a carrier will contain the defective version. By contrast, all the eggs or sperm of an individual in whom both gene copies are defective – and who, as a result, has haemochromatosis – will carry the abnormal gene.
To develop GH you have to inherit a defective gene or genes from your parents. The following 'family trees illustrate inheritance probability:
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The Celtic link
GH is sometimes described as The Celtic Curse - we prefer to know it as the celtic cause. Although Celtic Curse this is not a particularly attractive phrase, it does underscore the fact that those people with Celtic ancestry are far more likely to be affected - but you may have no idea that you have celtic ancestry - so don't be completely surprised when you get this diagnosis.
Many people with GH can immediately identify Celtic family roots. However it is important to understand that the condition can affect people of all ethnicities, it is just more prevalent in people with Celtic roots.
Thus there are much higher rates of GH in Scotland, Northern Ireland (especially), the North-West of England and the Republic of Ireland. The same applies to other parts of the world to where people from these areas subsequently migrated.
How recessive inheritance works when both parents are carriers (scenario 1) is also shown in this diagram:
In the light of this relatives of someone who has been diagnosed and who are at risk should be tested. This is particularly important in the case of brothers and sisters (siblings) as they stand at least a 1 in 4 chance of being affected. Parents, partners and children, should also be tested.
The Celtic link
GH is sometimes described as The Celtic Curse. Although this is not a particularly attractive phrase, it does underscore the fact that those people with Celtic ancestry are far more likely to be affected.
Many people with GH can immediately identify Celtic family roots. However it is important to understand that the condition can affect people of all ethnicities, it is just more prevalent in people with Celtic roots.
Thus there are much higher rates of GH in Scotland, Northern Ireland (especially), the North-West of England and the Republic of Ireland. The same applies to other parts of the world to where people from these areas subsequently migrated.
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Types of GH
Genetic haemochromatosis comes in several variants, depending upon genetic mutation. Each has its own characteristics.
HFE variants (common)
The most common type, known as HFE (or type 1) genetic haemochromatosis is present in around 1 in 150 people in England & Wales (C282Y Homozygous), 1 in 113 people in Scotland (C282Y Homozygous) and around 1 in 10 people in Northern Ireland (C282Y Homozygous) and Compound Heterozygous). HFE variants are not rare, but rarely diagnosed.:
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Compound heterozygous (H63d/S65C)
Non-HFE Variants (rare)
Over the years, other non-HFE causes of iron overload have been isolated. These are known as "non-HFE" variants as they are caused by genetic mutations associated with genes other than the HFE gene. These variants are also known as types 2, 3 and 4. Type 4 is also sometimes called Ferroportin Disease. The prevalence of non-HFE variants is under-studied but thought to be "rare" (affecting 1 in 30,000 people or fewer).
Overall, it is thought that around 160 genetic mutations can cause or contribute to iron overload, to varying degrees. There are also "molecularly undefined" variants, for which the genetic cause is unknown or unexplored, but where iron overload has been demonstrated. These variants are rare.
There may also be other genetic mutations which predispose people to iron overload. As medical research and our understanding of the human genome progress, these may become distinctly identified. In the meantime, our charity works to support anyone affected by genetic haemochromatosis, whatever its cause.
There are several known types of genetic haemochromatosis.
Getting Tested for Genetic Haemochromatosis
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In the UK, the NHS typically only tests for HFE (type 1) mutations in C282Y and H63D. This is known as a R95 test. The NHS Genomic Test Directory makes provision for people exhibiting symptoms of iron overload who have been tested for Type 1, to receive further testing for non-HFE causes of haemochromatosis. This is known as a R96 test.
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