The frequency of complications is largely underestimated in people carrying the genetic anomaly. A factual element to reorganize prevention in families at risk.
In European populations, the “HFE p.C282Y” mutation is the main cause of iron overload syndrome in hereditary hemochromatosis type 1. Iron overload and its complications are, however, preventable or can be treated with regular bleeding (no, no, they did not disappear with Molière). But the diagnosis of this disease is difficult and it is often late, at a stage when there are already complications.
In a European biobank (UK Biobank), one in 5 men carrying the homozygous p.C282Y mutation (mutation on both chromosomes) has a clinical complication related to iron overload, compared to those without p.H63D mutations (occurring at an average age of 63.8 years).
In women, a complication develops in only one in 10 women who carry the mutation. This study appeared in the BMJ.
Genetic study
The study was carried out on an English biobank (UK Biobank) comprising 451,243 volunteers, aged 40 to 70, and followed up for 9.4 years. In this population, 2890 people are ultimately homozygous for the p.C282Y anomaly (anomaly on the 2 paternal and maternal chromosomes). This corresponds to a frequency of 1 in 156 people in the general population, which confirms that it is the most common genetic disease.
However, hemochromatosis was only diagnosed in 21.7% of men and 9.8% of women at the end of follow-up (95% confidence interval: 19.5% to 24.1%, 281/1294) . Men homozygous for the p.C282Y mutation have a higher frequency of diagnosed hemochromatosis than those without the mutation (n=175,539).
Main complications
When we look at the frequency of complications of this overload disease appearing during the evolution in homozygous carriers of the anomaly.
It is essentially a disease of the liver (cirrhosis) (4.30, 2.97-6.18, p<0.001), diabetes mellitus (1.53, 1.16 to 1.98, P=0.002), rheumatoid arthritis (2.23, 1.51 to 3.31, P<0.001) or osteoarthritis (2.01, 1.71 to 2.36, P<0.001).
Complications underestimated
Previous studies had shown that, in hemochromatosis, less than 1% of people carrying the homozygous p.C282Y mutation developed frank clinical hemochromatosis, that is to say with complications (low penetrance). However, in this European Biobank, clinical hemochromatosis was finally diagnosed in 21.7% of male p.C282Y homozygotes and in 9.8% of female p.C282Y homozygotes, at the end of follow-up.
These diagnostic rates are comparable to those of another US biobank, conducted at seven North American medical centers (mean age 61.5 years). However, in the latter, at the age of 90, almost 50% of men and 25% of women are diagnosed with clinical hemochromatosis, testifying to the evolution with age and a sub- important assessment of the risk of chronic complications.
A diagnosis at the stage of complications
Hereditary hemochromatosis is characterized by an accumulation of iron in the organs and its clinical picture typically includes cirrhosis of the liver, diabetes and changes in skin color, but the diagnosis is usually made in the presence of chronic fatigue or arthropathy. .
There is also a risk of heart attacks, infections and the p.C282Y genotype is also associated with lower low density lipoprotein cholesterol levels.
The 1time genetic disease in frequency
Hereditary hemochromatosis is a disease related to iron overload. It is the most common genetic disease in people of European descent. Type 1 hereditary hemochromatosis is mainly attributable to two mutations of the HFE gene: 95% of those affected have a mutation in the p.C282Y gene (p.Cyst282Tyr) and 4% have the p.C282Y/p.Hist63Asp1 genotype.
The p.C282Y variant is present in 10-15% of populations of northern European ancestry, with approximately 1/150 people being homozygotes and the highest recorded genotype prevalence being in Ireland and Great Britain.
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