Jennifer Lovejoy, Arivale Chief Science Officer, PhD
The iron overload that results from hereditary hemochromatosis is associated with significant health problems, including liver disease, diabetes, joint damage, and fatigue. Yet despite it being the most common genetic condition in people of European ancestry, the US doesn’t have standard screening for either the genetic variants associated with hereditary hemochromatosis or blood levels of ferritin (a marker of iron stores). This means the condition often goes undetected until it has caused significant organ damage, a fact which led medical journalists to refer to it as a “stealth disease.”
Most cases of hereditary hemochromatosis are attributable to two mutations in the HFE gene: C282Y and H63D.
The earliest symptom of hemochromatosis is often joint pain, which is typically dismissed as simply a sign of aging or over-activity. Unfortunately, the longer the condition is ignored, the worse the consequences.
The risk of developing hemochromatosis is significantly higher in men than women (due to monthly blood losses in premenopausal women); however, both men and women have increased risk with aging if they have the HFE mutations.
Two recent studies from the University of Exeter in the UK reveal how serious – and common – the health consequences of hemochromatosis are. Both studies used data from the UK Biobank – a large dataset of community-living volunteers in the UK between the ages of 40 and 70.
The first study looked at over 450,000 participants to determine how common the diagnosis of hemochromatosis was in individuals with the C282Y or H63D risk genotypes and what chronic conditions were associated with these genotypes. The second study looked at data from approximately 200,000 UK Biobank participants to determine the association between the HFE variants and frailty, muscle loss, and chronic pain.
The first study found that 22 percent of men and 10 percent of women with two copies of the risky C282Y variant in the HFE gene were eventually diagnosed with hemochromatosis. Of these, 57 percent of men and 52 percent of women had abnormal liver enzymes, as well as higher rates of fatigue, joint pain, impotence (men), and diabetes. Joint pain was present in 20 percent of men and 13 percent of women. Although rates were low, there were also higher rates of hip replacements and liver cancer in people with two copies of the C282Y mutation.
Similarly, the second study found that men between 60 and 70 with the C282Y mutation were 23 percent more likely to have chronic pain and had twice the rates of low muscle mass and frailty compared to men without the mutation. Women with the C282Y mutation were nearly twice as likely to have frailty and had significantly higher rates of chronic hip, back, and knee pain than women without the mutation.
Hemochromatosis is a highly treatable disease when it’s caught early. Treatment consists of regular blood donation (“therapeutic phlebotomy”) until blood iron levels return to normal.
Unfortunately, if the iron overload is allowed to persist undetected, damage caused to the liver, pancreas, joints, and other organs is not reversible and can lead to significant health problems and reduced life expectancy.
The authors of the recent studies suggest public health agencies revisit their position on recommendations of early screening for HFE mutations, noting that “hereditary hemochromatosis is a strong candidate for precision medicine approaches to improve outcomes in late life.”
In Arivale’s member database, it’s not uncommon to see elevated levels of ferritin – often in conjunction with HFE mutations. Fortunately, most of the individuals identified by screening are still asymptomatic and can work with their physicians on a treatment plan to prevent long-term complications of iron overload. As a result, we agree that broader public screening for this treatable “stealth disease” makes great sense.
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[Arivale Hot Topics address health stories currently in the news. The Arivale Clinical Team’s commentary on these news articles is not a review of the scientific evidence, nor an endorsement of a specific study, and is not meant as official medical opinion.]