Screening for Fabry ‘important’ in chronic kidney diseases: Study
Such programs allow for prompt diagnosis and timely treatment of patients
Among people receiving medical care for chronic kidney diseases, a small fraction have Fabry disease, a new study highlights.
To ensure these patients get optimal treatment, it’s critical to have screening programs in place to provide a prompt diagnosis — especially early on — according to researchers.
“Although the overall prevalence of [Fabry disease] is low in patients with kidney involvement, screening, especially in patients who have not yet undergone kidney replacement therapy, is important, in order to provide timely and effective treatment interventions,” the scientists wrote.
Researchers acknowledge that Fabry prevalence remains low
Fabry disease is caused by mutations in the GLA gene, resulting in abnormally low activity of the protein alpha-galactosidase A, known as Gal A. Dysfunction of Gal A results in the toxic buildup of certain fatty molecules, which causes organ damage that drives disease symptoms.
The kidneys often are the hardest-hit organ in Fabry, and kidney problems may be the first sign of the disease for some patients. Among individuals receiving medical care for kidney problems, screening for Fabry can help identify the disease and facilitate appropriate treatment.
In this study, researchers conducted a meta-analysis aiming to estimate exactly how common is Fabry disease among people receiving care for kidney problems. In this type of analysis, scientists pool data from multiple previously-published studies and analyze it collectively.
Their analysis included data from 55 studies covering more than 84,000 people with chronic kidney diseases.
Mutations in the GLA gene were identified in 251 of these individuals, though in 37.8% of these cases the mutation was benign — meaning the mutation doesn’t disrupt Gal A activity and so isn’t thought to cause overt Fabry disease. Among the remaining mutations, 31.7% were linked with classical Fabry and 15.5% with late-onset Fabry, while the rest were mutations whose clinical significance isn’t yet certain.
Based on data from across the various studies, the researchers estimated that Fabry disease was present in about 0.1% of patients undergoing dialysis, and in about 0.28% of patients undergoing kidney transplant. Among patients who had kidney disease but weren’t receiving active kidney-targeted treatments, the prevalence of Fabry disease was 0.17%.
”Screening studies remain crucial in the identification of positive cases and providing timely treatment, even though the overall prevalence of patients with a definitive diagnosis of [Fabry disease] within the kidney high-risk population is relatively low.
Collectively these data emphasize the importance of screening people with kidney disease to allow proper diagnosis for the small but notable number of Fabry patients.
“Screening studies remain crucial in the identification of positive cases and providing timely treatment, even though the overall prevalence of patients with a definitive diagnosis of [Fabry disease] within the kidney high-risk population is relatively low,” the scientists wrote.
The GLA gene is located on the X chromosome, one of the two sex-determining chromosomes: males have one X and one Y, while females have two X chromosomes. Because females have a second copy of the GLA gene on that second X chromosome, Fabry disease is much rarer in women than in men.
In line with this, the researchers found that men with kidney problems were much more likely than women to be positive for Fabry disease. However, the scientists also noted that many studies didn’t include female patients, so there’s substantially less data from which to draw conclusions.
The scientists therefore stressed that it’s important for future studies and screening programs to include people of all genders and sexes.
“The limited inclusion of females in various studies is attributed to inadequate understanding of the [Fabry disease] phenotype in female heterozygotes [people with one GLA mutation and a second healthy copy] and the diagnostic challenges of evaluating disease burden of females in this X-linked disease,” the scientists wrote.