Prevalence of Fabry disease in dialysis patients: Western Australia Fabry disease screening study - the FoRWARD study

• Main Authors: Sadia Jahan, Subashini Sarathchandran, Shamina Akhter, Jack Goldblatt, Samantha Stark, Douglas Crawford, Andrew Mallett, Mark Thomas
• Format: Article
• Language: English
• Published: BMC 2020-01-01
• Series: Orphanet Journal of Rare Diseases
• Subjects: Fabry disease; Screening; Dialysis; Dried blood spot; α-GAL-A
• Online Access: https://doi.org/10.1186/s13023-019-1290-3

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 alpha-galactosidase-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.