Haemochromatosis : The Celtic Curse.

Haemochromatosis is the UK and Irelands most common inherited condition and is thought to be severely underdiagnosed. The prevalence of haemochromatosis among individuals of white ancestry is estimated to be approximately 1 in 300, notably observed across Europe, Australia, and other nations with significant populations of Celtic descent¹, hence the colloquial name – The Celtic Curse. However, while haemochromatosis is more common in these populations, it can affect people of any ethnicity or background.

Haemochromatosis is a genetic disorder that over time causes an overload of iron within the body that can lead to conditions such as cirrhosis, liver cancer, diabetes, arthritis, and heart failure². With an NHS expenditure of around £487 million annually³, this condition carries a significant burden on healthcare services.

While the name is complicated, our message is simple: Early identification saves lives!

• Aproximately 9 million people in the UK are estimated to harbour 1 of the 5 genetic mutations associated with Genetic Haemochromatosis (GH)³.
• £ 487 million annual NHS expenditure – Over 55% of which is used in treatments for GH-induced liver disease, liver cancer, diabetes, arthritis and more³.
• In Northern Ireland, as many as 1 in 10 people are directly affected by GH⁴.
• In the UK, estimates claim that 380,000 people are directly affected by haemochromatosis, however only 14,000 people have been identified by the NHS⁵.

When we think of iron, many of us think of swords, shields, hammers, and other tools. Echoing the spirit of the time, the Iron Age (circa 1200-1000 BC) saw the use of iron not only as a tool but surprisingly as a medicinal remedy for various ailments⁶, although healers of the time could not have known about its vital function in the body

More recently, you might think of car parts, infrastructure, or hefty gates. However, iron is also an essential mineral in your body, required for various processes including DNA synthesis and oxygen transport⁷.

In contrast to other minerals in the body, iron excretion is an unregulated process, meaning the control of iron levels is exclusively the responsibility of absorption⁷. Some believe this is due to the historical lack of iron in the human diets resulting in an evolutionary propensity for iron accumulation.

Until the 1920s, a significant number of individuals, particularly adolescent females, experienced green sickness, or chlorosis (derived from the Greek for greenish-yellow) – a condition now widely recognised as iron deficiency⁶.

When iron is excreted, it’s in unregulated amounts in the form of sweat, during menstruation, through the shedding of skin and hair cells or through the turnover of enterocytes (cells of the small intestine crucial in nutrient absorption)⁷.

Most of our iron is found in haemoglobin, the protein in red blood cells responsible for transporting oxygen around the body⁷ – oxygen binds to the iron, or the haem groups, of haemoglobin.

Within one haemoglobin protein are four haem groups each containing an iron molecule, enabling the reversible binding of four oxygen molecules. This provides an efficient means of transporting oxygen throughout the body.

Iron is exceptionally well-suited for its crucial role in various biological processes due to a combination of unique factors. Its distinctive chemistry allows it to undergo oxidation-reduction reactions, which are pivotal for functions such as oxygen transport, energy production, and DNA synthesis.

The adaptable electronic configuration of iron enables it to efficiently participate in electron transfer reactions and serve as a cofactor in enzymes crucial for metabolic pathways.

Additionally, iron’s status as the 4th most abundant element in the Earth’s crust⁶ ensures its widespread availability, facilitating easy access and assimilation by living organisms. This abundance is particularly significant as iron plays a central role in essential physiological functions such as oxygen binding in haemoglobin, ATP generation in the electron transport chain, DNA replication and repair, and enzymatic processes vital for overall cellular health.⁶

Haemochromatosis is an autosomal recessive disorder¹. Briefly, for a person to suffer with this condition, they need to have 2 faulty copies of the gene; harbouring only one faulty variant means that the other working gene can pick up the slack. If an individual only has 1 faulty copy and 1 working copy they are considered a carrier – there is a 50% chance they’ll pass this gene on to their offspring. For a more detailed explanation, check out our blog, Genetic Inheritance and Conditions. In haemochromatosis, these variants, or mutations, occur in the gene responsible for the HFE protein. This mutant HFE protein causes an increase in iron absorption and the subsequent deposition of iron into various organs².

The most common mutation responsible for haemochromatosis is the C282Y variant. This variant also causes more severe symptoms than the next most common variant, H63D¹. Those who carry two copies of the C282Y variant (homozygous) are at a much higher risk of iron overload and the associated complications, shown in the table below¹. Its also important to note that these complications, particularly those related to the liver and pancreas, can be exacerbated by high alcohol intake and viral hepatitis¹.

Individuals that harbour homozygous H63D variants are generally asymptomatic, however, if iron levels increase above normal, investigation is required as there may be another reason for this rise⁸.

Some people harbour a copy of each of these variants (C282Y and H63D), referred to as compound heterozygous. 95% of people with this genotype are asymptomatic, however, the remaining 5% of patients should seek to monitor their iron levels every few years to avoid any severe complications⁸.

If identified before organ damage has occurred, treatment of haemochromatosis is straightforward and successful. Generally, restricted diets are not recommended. However, in some cases, patients will be encouraged to reduce their intake of iron through things like red meat, poultry, and pork, which contain high levels of iron and are easily absorbed.

Some foods like leafy greens and dairy products or tea and coffee can help slow down the absorption of iron and may be considered along with foods high in iron⁸.

Testing at Randox Health

At Randox Health, we offer genetic testing to determine if you’re at high risk of haemochromatosis with a risk assessment completed and results returned within 7-14 days. Many cases of haemochromatosis are never diagnosed⁹, likely resulting in many cases of the other conditions discussed in this article.

Early identification allows the treatment and the prevention of a variety of forms of ill health that can result from iron overload. Once your results are available, you’ll get a genetic risk report via email, which will show a breakdown of your results and explain exactly what they mean. For more information, visit our website at https://randoxhealth.com/en-GB/in-clinic/haemochromatosis