Hemochromatosis: more common than first thought

Hereditary hemochromatosis type 1 is a disease of iron overload caused predominantly by a mutation in the homeostatic iron regulator (HFE) gene, p.Cyst282Tyr (p.C282Y). The incidence of the mutation is most common in people of northern European descent – with 1 in 8 people being carriers, making it the most common genetic condition in this population. Approximately 1 in 150 people are homozygotes, although a previous study suggested that only about 1% of homozygotes went on to develop “frank clinical hemochromatosis” involving liver disease. The overload of iron results in iron deposition in the liver, pancreas and joints, causing liver disease (cirrhosis and cancer), fatigue, diabetes and arthritis. Diagnosis if often missed or delayed because of the insidious onset of symptoms that often only become apparent later in life and which can easily be attributed to other causes. Currently, if hemochromatosis is suspected, diagnosis is made by testing for high blood iron levels. Genetic screening is limited only to close family members of hemochromatosis patients because of the suggestion of low general penetrance of the disease. The damaging effects of iron overload can be easily prevented if the disease is diagnosed early enough, largely by withdrawing blood on a regular basis. However, a recent study by Pilling et al. of nearly 500 000 UK Biobank volunteers is changing the way we think about the condition (Pilling LC, et al. Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank. BMJ 2019; 364: k5222). This study involved a far larger number of people than previous studies, as well as involving older people – important for monitoring a disease where the effects are cumulative. The authors found a much higher prevalence of hemochromatosis and associated conditions than expected. Of the p.C282Y homozygous participants, 21.7% of men and 9.8% of women were eventually diagnosed with hemochromatosis. The results of this study have prompted the UK National Screening Committee to announce that it will review the evidence for hemochromatosis screening at its next routine review. However, in the meantime, we are actually in the fortunate position that this disease is easy to test for and easy to treat. No new methodology is needed, but simply a change in pathway, as advocated by Dr Ted Fitzsimons (consultant hematologist at Gartnavel Hospital, Glasgow, UK): if the results of a serum ferritin test are high and the patient is of northern European descent, the blood iron levels should automatically be tested. If this result is also high, then the patient should be screened for hemochromatosis. Many people have a lot to gain from this simple change.