S AKHTER1, S ALEXANDER1, J GOLDBLATT2, S STARK3, D CRAWFORD1, M THOMAS1
1Dept of Nephrology, Royal Perth Hospital, WA; 2Genetics WA (retired); 3National Referral Laboratory (NRL), Adelaide, SA;
AIM: To determine the prevalence of undiagnosed Fabry Disease (FD) in Western Australian (WA) patients on dialysis.
BACKGROUND: FD is a multisystem X-linked lysosomal storage disease due to GLA gene mutations, causing alpha-galactosidase A deficiency (α-GAL A). It presents with peripheral pain & rash in childhood, then premature death from cerebral, cardiac or renal disease, but diagnostic delay averages 10 years. Prevalence of classic symptomatic disease ≈ 1:50,000; screening high-risk populations produces variably greater rates, prior studies reporting 0-1.7% in dialysis populations.
METHODS: A cross-sectional study of all patients on dialysis in WA who provided informed consent were screened for α-Gal A levels by dried blood spot samples (NRL). Low levels were repeated with GLA gene mutation analysis by next generation sequencing. Ethics approval was granted by Royal Perth Hospital REG 14-136; site-specific approval was granted from appropriate authorities; on ANZ Clinical Trials Registry U1111-1163-7629.
RESULTS: Between February 2015 & May 2017, α-Gal A activity was performed on 375 of 1,100 patients, at 12 of 21 dialysis sites. 37 patients had initial low α-Gal A; repeat testing w& GLA genotyping showed NO confirmed FD cases. False low α-Gal A cases were particularly associated with one private unit (?poor sample handling); other cases had relatively more malnutrition & inflammation (?impaired protein synthesis). During the same time period, 19 confirmed new FD cases were added to total known 45 WA FD cases: 2 cardiac, 1 renal, 1 rheumatological, & 15 through cascade genetic testing.
CONCLUSION: Interim analysis of WA dialysis population has shown a prevalence of 0% undiagnosed FD; false positives may occur through sample handling or malnutrition.