A MALLETT1,2,3, P KEAREY1,4, A CAMERON1,4, H HEALY1,2,4, C DENARO1,5, M THOMAS6, V LEE7,8, M FULLER9, W HOY1,4
1The University of Queensland, Brisbane, Australia, 2Kidney Health Service, Royal Brisbane And Women’s Hospital, Brisbane, Australia, 3The KidGen Collaborative, Australian Genomics Health Alliance, Melbourne, Australia, 4CKD.QLD and NHMRC CKD.CRE, The University of Queensland, Brisbane, Australia, 5Department of Internal Medicine and Aged Care, Royal Brisbane and Women’s Hospital, Brisbane, Australia, 6Department of Nephrology, Royal Perth Hospital, Perth, Australia, 7Department of Renal Medicine, Westmead Hospital, Sydney, Australia, 8Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia, 9Genetics and Molecular Pathology Laboratory, SA Pathology, Adelaide, Australia
Aim: To define the prevalence of Fabry Disease (FD) amongst Queensland patients with Chronic Kidney Disease (CKD).
Background: FD is a rare, genetic disorder that results in the absence or deficiency of alpha-galactosidase A, leading to accumulation of globotriaosylceramide in cells and tissues. The main causes of associated mortality and morbidity are renal, cardiac, and cerebrovascular manifestations. General population prevalence is estimated at 1:40,000 (0.0025%). Dialysis population prevalence is estimated at 0.12% to 0.36%. Little is known about the prevalence of FD amongst wider CKD populations. Although FD is X-linked, affected females can have variable disease manifestations. Prevalence amongst women is unclear.
Methods: A prospective cross-sectional study of FD prevalence amongst CKD patients in public, specialty Queensland renal services was undertaken across seven sites from October 2017 to August 2019. 3,000 patients across CKD Stages 1-5/5D/5T were screened using dried blood spot (DBS) testing. Repeat DBS and/or Lyso-GB3 testing was employed where results were inconclusive. FD was confirmed through diagnostic GLA genetic sequencing.
Results: 6 unrelated cases (0.20%) of FD were identified. 3/6 with a previously identified FD diagnosis (100% sensitivity). 3/6 with a new diagnosis of FD as a result of study participation. 5/6 were male, representing 0.3% and 0.08% of all male and female participants respectively. All newly diagnosed cases were male with 2/3 being CKD Stage 5T, and 1/3 being CKD Stage 5D. An additional 28 at-risk family members were identified.
Conclusions: Our results support the potential feasibility and utility of a cascade screening strategy for FD in adult patients with CKD. Further, we confirm that a significant proportion of prevalent cases of FD amongst those with CKD remains undiagnosed.
Prof Andrew Mallett is a Nephrologist with a special interest in inherited kidney disease and nephrogenetics. After graduating from JCU he completed physician and adult nephrology training at MBH, RBWH and PAH. Prof Mallett has undertaken a Churchill Fellowship and been a recurrent Visiting Fellow at Addenbrooke’s Hospital and the Cambridge Institute for Medical Research. His PhD (UQ) in nephrogenetics involved extensive national and international collaboration. Prof Mallett is Director of Clinical Research and Nephrologist at Townsville University Hospital and co-leads the Queensland Conjoint Renal Genetics Service. He is the National Director of the KidGen Collaborative and two AGHA Flagships.