Prevalence of Fabry disease in dialysis patients: Western Australia Fabry disease screening study - the FoRWARD study
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(2020) 15:10
RESEARCH
Open Access
Prevalence of Fabry disease in dialysis patients: Western Australia Fabry disease screening study - the FoRWARD study Sadia Jahan1,2 , Subashini Sarathchandran3, Shamina Akhter3, Jack Goldblatt4, Samantha Stark5, Douglas Crawford3, Andrew Mallett1,2 and Mark Thomas3*
Abstract Aim: To determine the prevalence of undiagnosed Fabry Disease (FD) in Western Australian (WA) patients undergoing dialysis. Background: FD is a multisystem X-linked lysosomal storage disease caused by deficient activity of alphagalactosidase-A (α-GAL-A). Affected individuals are at risk of developing small-fibre neuropathy, rash, progressive kidney disease, hypertrophic cardiomyopathy and ischaemic stroke. Diagnosis is often delayed by years or even decades. Screening high risk population such as dialysis patients may identify patients with undiagnosed Fabry disease. Methods: A cross-sectional study was undertaken of all adult patients receiving dialysis in WA, without previously known FD. After informed consent they were screened for α-GAL-A activity by dried blood spot samples. Low or inconclusive activity were repeated via Centogene in Rostock, Germany with GLA genetic analysis. Ethics approval was granted by Royal Perth Hospital Human Research Ethic Committee REG 14–136; site-specific approval was granted from appropriate authorities; ANZ Clinical Trials Registry U1111–1163-7629. Results: Between February 2015 & September 2017, α-GAL-A activity was performed on 526 patients at 16 dialysis sites. Twenty-nine patients had initial low α-GAL-A; repeat testing & GLA genotyping showed no confirmed FD cases. The causes of false positive rates were thought to be secondary to impaired protein synthesis due to patient malnutrition and chronic inflammation, which is common among dialysis patients, in addition to poor sampling handling. Conclusion: Analysis of this dialysis population has shown a prevalence of 0% undiagnosed FD. False positives results may occur through impaired protein synthesis and sample handling. Keywords: Fabry disease, Screening, Dialysis, Dried blood spot, α-GAL-A
Background Fabry disease (FD) is a multisystem X-linked lysosomal storage disease caused by deficient activity of alphagalactosidase-A (α-GAL-A). This results in an accumulation of glycosphingolipids with terminal α-D-galactosyl residue particularly globotriaosylceramide and globotriaosylsphingosine [1] in organs, namely kidney, heart, peripheral nerves and brain. Symptoms of FD generally * Correspondence: [email protected] 3 Department of Nephrology, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia Full list of author information is available at the end of the article
emerge during childhood or adolescence with neuropathic pain crisis (acroparesthesia), angiokeratomas, ophthalmologic abnormalities, hypohydrosis and gastrointestinal symptoms. Major organ involvement is from 20 to 30 years of age onwards, leading to chronic kidney disease, hypertrophic/dilated cardiomyopathy, deafness and cerebrovascular
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