A large recent study has found that some people with genetic variants linked to the common iron overload condition haemochromatosis experience substantially higher levels of liver, musculoskeletal and brain disease than previously reported, particularly in older age.
Haemochromatosis causes iron to build up in the body, potentially damaging joints and organs. The research, led by the University of Exeter and supported by the National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre, found higher rates of disease and mortality in men, especially after age 65.
Published in BMJ Open, the study analysed data from more than 450,000 participants of European ancestry in UK Biobank over 13 years. It is the largest study of disease outcomes linked to haemochromatosis and the first to examine clinical outcomes up to age 80, including in people who were undiagnosed at the start of the study.
Dr Janice Atkins, Senior Research Fellow at the University of Exeter, said: “Haemochromatosis is the most common genetic disorder in people of Northern European ancestry, yet we are still learning the extent to which it causes harm. Our study reveals higher levels of death and organ and joint damage than previously known.”
Among the 2,902 participants (0.6%) carrying two copies of the high-risk C282Y genetic variant, only 12% of men and 3.4% of women had been diagnosed with haemochromatosis at baseline.
By age 80, 33.1% of men with the variant had died, compared with 25.4% of those without it. They were also more likely to have undergone joint replacement (27.9% vs 17.1%), developed liver disease (20.3% vs 8.3%), and experience delirium, non-Alzheimer’s dementia and Parkinson’s disease.
Women with both variants also showed higher rates of liver disease (8.9% vs 6.8%), joint replacement and delirium by age 80.
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Haemochromatosis is more common in men and among people of Northern European ancestry. Around 175,000 UK men of European ancestry are estimated to carry the two gene variants responsible for the condition. Often called the “Celtic curse”, it is particularly prevalent in Celtic populations. Ireland has one of the highest rates, if not the highest, of people pre-disposed to the condition in the world.
Reliable blood and genetic tests can identify those at risk. Symptoms such as fatigue, muscle weakness and joint pain are often mistaken for normal ageing. Once diagnosed, the condition can usually be managed through regular blood removal, similar to blood donation, to reduce iron levels.
Professor David Melzer, who led the research team, said the findings highlight the need for earlier diagnosis, as many people are identified only after organ damage has occurred. He also noted that people with milder genetic variants showed no increased risk of fatigue, liver fibrosis, diabetes or arthritis, supporting evidence that these variants are generally benign.
Study co-author Dr Jeremy Shearman, Consultant Hepatologist and Gastroenterologist at South Warwickshire University NHS Foundation Trust, said the findings support wider use of targeted genetic testing to enable earlier diagnosis and treatment of this common but manageable condition.
Source:
HFE genotypes, haemochromatosis diagnosis and clinical outcomes at age 80 years: a prospective cohort study in the UK Biobank. BMJ Open, 2024; 14 (3): e081926 DOI: 10.1136/bmjopen-2023-081926