Most conversations about iron are about having too little. Haemochromatosis is the opposite: an inherited condition in which the body absorbs more iron from food than it needs, and the extra slowly builds up over many years. The NHS notes that it most often affects people of white northern European background and is particularly common where many people have a Celtic background, such as Ireland, Scotland and Wales. For people with that heritage, or with a relative who has the condition, the HFE gene test and the Iron Overload Profile are worth understanding.
What haemochromatosis is
The NHS describes haemochromatosis as a condition caused by a faulty gene that affects how the body absorbs iron from the diet. If iron builds up and is not treated, it can affect the liver, joints, pancreas and heart over time. Symptoms usually start between the ages of 30 and 60 and can be vague: tiredness, weight loss, weakness, joint pain, brain fog or changes in mood. In men it can cause erectile problems, and in women irregular or missed periods. Because these symptoms are common and have many causes, blood tests are what bring iron overload to light.
The good news, in the NHS's words, is that when the condition is found and treated early on, it does not affect life expectancy and is unlikely to cause serious problems. Treatment usually involves regularly removing some blood, a procedure called venesection.
The HFE gene and its two common variants
Most haemochromatosis in people of northern European descent is linked to a gene called HFE. The HFE gene (Haemochromatosis) - common mutations C282Y + H63D test in the BPR catalogue looks for the two most common variants:
- C282Y: the variant most strongly linked to iron overload. Having two copies, one from each parent, is the genotype most often found in people with haemochromatosis (Fitzsimons et al., 2018).
- H63D: a milder variant. On its own it rarely leads to significant iron build-up, but it may matter in combination with C282Y (Kowdley et al., 2019).
Copies, carriers and risk
The NHS explains it simply. If you inherit only one copy of the faulty gene, you will not get haemochromatosis, but you could pass the gene on to your children. If you inherit two copies, you are at risk, but you will not necessarily develop the condition. Only some people with two copies ever do. A large UK Biobank study that followed people up to the age of 80 found that two copies of C282Y were linked with more haemochromatosis-related health problems over time, which is why the result is worth knowing and discussing (Lucas et al., 2024).
The blood markers: is iron actually building up?
A gene result tells you about risk. Blood markers tell you what is happening now. The two most useful are:
- Transferrin saturation: how much of the blood's iron-carrying capacity is in use. It tends to rise first when the body absorbs too much iron.
- Ferritin: the iron store. It rises as iron accumulates, but also with inflammation, liver conditions and alcohol, so a high ferritin alone does not mean iron overload (Cullis et al., 2018).
British guidance describes the combination of raised transferrin saturation and raised ferritin as the usual reason to consider HFE testing (Fitzsimons et al., 2018).
Which test answers which question?
Iron Overload Profile
The Iron Overload Profile brings the two sides together. LML lists iron, ferritin, transferrin saturation, total iron-binding capacity and the HFE gene in one request. It suits someone who wants to see both the current iron picture and the genetic background at once.
HFE gene test on its own
Useful when the iron markers are already known, or when a close relative has haemochromatosis. The NHS suggests talking to a GP if a parent or sibling has the condition, even without symptoms. US and British guidance both support testing first-degree relatives of people with HFE haemochromatosis (Kowdley et al., 2019; Fitzsimons et al., 2018).
Iron Status Profile or Ferritin
Useful for follow-up of the blood markers over time, without repeating the gene test.
