Haemochromatosis: when the body stores too much iron

Haemochromatosis: When the Body Accumulates Too Much Iron

Haemochromatosis is a hereditary condition where the gut absorbs more iron than the body needs. Over years, this excess iron can be stored in the liver, pancreas, heart, joints, and skin. Carrying the genetic predisposition is not the same as having clinical disease: the gene variant does not necessarily lead to iron overload with organ damage. Adams, Jeffrey and Ryan describe that haemochromatosis is both overdiagnosed in people without iron overload and underdiagnosed in others, and that early genetic diagnosis and phlebotomy can prevent the most serious complications such as cirrhosis, liver cancer and death (Lancet 2023;401(10390):1811-1821, PubMed). Carrying the predisposition is not the same as developing disease.

The diagnosis can be made late, after years of non-specific fatigue, joint pain, or elevated liver enzymes.

What are the symptoms?

Initially, often nothing. Iron accumulation takes decades, and symptoms typically appear after the age of 40 in men and later in women, as menstruation and pregnancy protect by drawing iron out of the body.

The first signs often include:

• Persistent, unexplained fatigue
• Joint pain, particularly in the index and middle fingers ("iron grip"), the base of the thumb, and the hips
• Bronze-coloured or grey-brown skin
• Loss of libido and, in men, erectile dysfunction
• Chest pain or shortness of breath
• Abdominal pain in the right side below the ribs

Later stages can lead to cirrhosis, diabetes ("bronze diabetes"), heart problems, and an increased risk of liver cancer. The key is that the risk of these complications can be reduced substantially when the diagnosis is made and treatment started before organ damage has occurred. Treatment is not a guarantee, and damage that is already present, such as cirrhosis, does not reverse.

Why does it happen?

In most cases, haemochromatosis is caused by a mutation in the HFE gene, most commonly the variant known as C282Y. If you have inherited one copy from each parent (homozygous), you are at risk of developing iron overload. A single copy (heterozygous) usually does not cause the disease.

Normally, the body regulates iron absorption through a hormone in the liver called hepcidin. In haemochromatosis, this signal does not function properly, and the gut continues to absorb iron even when stores are full. Over decades, the iron pool grows, and once it becomes large enough, organs begin to suffer damage.

How is it diagnosed?

Diagnosis is straightforward if it is considered at all:

1. Blood tests: Transferrin saturation over 45 percent and elevated ferritin is the classic combination. Transferrin saturation is the most specific finding.
2. Genetic test: Detection of C282Y homozygosity confirms the hereditary form.
3. Liver biopsy or MRI with iron quantification: Used in individuals where the degree of liver damage needs to be assessed, especially if ferritin is very high or if liver enzymes are elevated.

If you are an adult with a first-degree relative who has haemochromatosis, discuss genetic testing and iron studies with your doctor or with clinical genetics, even if you feel well. Whether and when to test is an individual medical and genetic counselling decision. An HFE genotype is not in itself iron overload or organ involvement; that is clarified with transferrin saturation, ferritin and an overall assessment. Detection before organ involvement is generally associated with a better course, but the course depends on the individual.

Treatment

The treatment is simple and effective. It is called phlebotomy: a bag of blood is drawn, just like a blood donation. Since blood contains iron, this gradually depletes the body's iron stores.

The typical course involves:

• Depletion phase: repeated venesections until ferritin is around 50 micrograms/litre, the target EASL states for this phase. How closely the sessions are spaced is set by the treating doctor, based on haemoglobin, iron measurements and how you feel. With very high initial values the phase can run for a long time.
• Maintenance: 2-4 blood draws per year for life to keep ferritin levels low.

In Denmark, you can become a blood donor despite having haemochromatosis, which makes the treatment meaningful for others too.

Diet plays a minor role, but it is wise to avoid iron supplements, avoid vitamins with iron, slightly limit red meat, and reduce alcohol intake as it further stresses the liver. Vitamin C increases iron absorption and should not be taken as a supplement with meals.

When should you see a doctor?

Have your transferrin saturation and ferritin levels checked by your GP if you have:

• A first-degree relative with haemochromatosis
• Unexplained joint pain in your fingers and hips
• Unexplained elevated liver enzymes
• Fatigue combined with bronze-coloured skin
• Early-onset diabetes without obesity
• Unexplained reduced libido or erectile dysfunction

Blood tests are inexpensive and can save you many years of symptoms.

Frequently Asked Questions

Can women also get haemochromatosis? Yes, but typically later than men, because menstruation and pregnancy draw iron out of the body. After menopause, iron begins to accumulate.

How many blood draws should I expect? This depends on how high your ferritin is at the start. A person with ferritin at 1500 might need 30-40 blood draws over the first year. With ferritin around 500, it goes much faster.

Can I drink coffee and eat iron-rich foods? Coffee and tea actually inhibit iron absorption and are fine to drink with meals. You don't need to panic about ordinary food. The important thing is not to supplement with iron and to keep alcohol intake down.

Will liver and joint pain improve with treatment? Liver enzyme levels can normalise during treatment. Liver fibrosis can regress after treatment in some patients. Advanced fibrosis or cirrhosis can also regress in some cases, but this is not certain; people with advanced liver damage still need specialist follow-up and relevant cancer surveillance according to current guidelines (Khan S, Saxena R. Adv Anat Pathol 2021;28(6):408-414, PubMed). Unfortunately, joint pain is the symptom group that responds least well to treatment, which underscores the value of early diagnosis.

Sources

1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on haemochromatosis. J Hepatol. 2022;77(2):479-502.
2. Adams PC, Jeffrey G, Ryan J. Haemochromatosis. Lancet. 2023;401(10390):1811-1821. PubMed
3. Sundhed.dk. Hæmokromatose (lægehåndbogen).
4. Kowdley KV, Brown KE, Ahn J, Sundaram V. ACG Clinical Guideline: Hereditary Hemochromatosis. Am J Gastroenterol. 2019;114(8):1202-1218.

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This article provides general information and does not replace a medical consultation. Contact your GP if you experience symptoms.