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Late-onset Fabry Disease May Be More Common Than Estimated




A genetic analysis showed that mutations likely to cause Fabry disease, particularly those associated with late-onset disease, were more common in the adult UK population than the estimated prevalence of the disease itself.

The findings suggest that the prevalence of late-onset Fabry disease may be higher than estimates, according to the researchers.

The study, “Prevalence of Fabry-pathogenic variants in the UK Biobank” was published in Journal of Medical Genetics.

Fabry disease is a genetic disease caused by mutations in GL The gene, which provides instructions for making an enzyme responsible for breaking down a fatty substance called globotriaosylceramide (Gb3). This results in Gb3 accumulating to toxic levels in many organs, causing symptoms of the disease.

To date, there are more than 950 disease-causing mutations in GL has been recognized. Fabry disease is classified into two forms, depending on how severely these mutations affect the activity of the enzyme alpha-galactosidase A (Gal A).

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Mutations that result in less than 3% of normal enzyme activity cause the more severe classic type of Fabry disease, which usually occurs in childhood or adolescence. Mutations that generate an enzyme with some residual activity (3%-15% of normal) lead to a later, less severe form of the disease.

Current estimates of the global prevalence of Fabry disease range from 1 in 40,000 people to 1 in 170,000. Newborn screening studies indicate that the number is higher.

The scientists used samples from the UK Biobank to determine the prevalence of variants known to cause Fabry disease and associated symptoms.


The Biobank contains demographic, phenotypic and clinical information as well as biological samples from more than 500,000 people, aged 37 to 73, recruited across the UK between 2006 and 2010.

The researchers created two groups based on age and health conditions that Fabry suggested. The first group included men under the age of 60 with chronic kidney disease, heart disease and hearing loss. The second was men under the age of 60 with chronic kidney disease, heart disease and cerebrovascular disease.

Genetic analysis was performed on 200,643 individuals from Biobank in the United Kingdom.

“This is one of the largest screening efforts ever undertaken by Fabry, and is the largest to our knowledge…in a non-selected adult population including men and women,” the researchers wrote.

The results showed that 36 people carried 81 genetic variants of GLA, Including eight rare species. Almost all variants were associated with late Fabry onset. The most common – C 644A>G – It was associated with later cardiac symptoms.

The prevalence of disease-causing variants in this population was 1 in 5,573. As only one variant, called c.718_719delwas associated with the classic form of the disease, the prevalence of classic Fabry disease was estimated to be 1 in 200,643.

Only three people with disease-causing variants had medical records indicating Fabry disease. All patients with evidence of a current diagnosis of Fabry have a disease-causing variant.

The researchers note that although AD 1067 AD > A The variant is associated with classic Fabry disease in some reports, and none of the four participants had this type of Fabry disease or symptoms suggestive of disease. This refers to genetic variants GL It has variable influence, which means that not all patients with a particular variant will have disease symptoms.

The authors conclude that “disease-causing GLA variants from Fabry are more prevalent in an unselected population sample than the reported prevalence of Fabry disease.” “Because genetic screening is so widely used, it will be necessary to understand the prevalence of these variants to inform clinical surveillance strategies and to identify those who would benefit from treatment.”


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