Fabry disease in the haemodialysis population: outcome of a UK screening study (SoFAH)
Ng, KP Sandhu, M Banerjee, D Burton, JO Crowley, L Doulton, T Hameed, MA Hamer, R Menon, M Nicholas, J
Ng, KP
Sandhu, M
Banerjee, D
Burton, JO
Crowley, L
Doulton, T
Hameed, MA
Hamer, R
Menon, M
Nicholas, J
Affiliation
University Hospital Derby and Burton NHS Foundation Trust; University Hospital Birmingham NHS Foundation Trust; St George's University of London NHS Foundation Trust; The Dudley Group NHS Foundation Trust et al
Other Contributors
Publication date
2025/05/26
Subject
Research Projects
Organizational Units
Journal Issue
Abstract
Fabry disease (FD) is an X-linked inherited disorder with an estimated prevalence among the end-stage kidney disease (ESKD) population of 0.3% in men and 0.1% in women [1]. Due to its non-specific manifestations, FD (especially the later-onset variant) is often underdiagnosed [2]. We aimed to estimate its prevalence in a large haemodialysis (HD) population in the UK. This is a cross-sectional, multicentre study of eight renal centres in the UK. All male participants were tested via dried blood spot alpha-galactosidase A (AG) enzyme and globotriaosylsphingosine (Lyso-Gb3) assays. If either the AG (? 2.8 �mol/L/H) or Lyso-Gb3 (? 3.5 ng/mL) level was abnormal, genetic testing for GLA variant was performed. All females had AG, Lyso-GB3 and genetic tests. In total, 1325 consented to participate in the study. The mean age of the participants was 64 (SD 15) years, 67% were male, 64% were of white ethnicity, the duration of dialysis was 32 (IQR 56) months, and 32% underwent renal biopsy. Diabetic nephropathy (28%) was the most common cause of ESKD, whereas 21% had an unknown aetiology. A total of 1,295 had both AG and Lyso-Gb3 tests, whereas 573 had GLA genetic tests. Among the 14% (n = 186) with an AG level ? 2.8 �mol/L/H, 48 were female and 138 were male, all of whom had Lyso-Gb3 < 3.5 ng/mL. Only 3 (0.2%) had abnormal Lyso-Gb3 but all had normal AG and negative genetic tests. Two females were found to have likely benign, non-pathogenic GLA variants: heterozygous c.937G > T (p.(Asp313Tyr) and heterozygous c.1102G > A (p.(Ala368Thr)). Despite the implementation of stringent screening criteria, we did not identify any new confirmed cases of Fabry disease in this large UK haemodialysis population.
Citation
Ng KP, Sandhu M, Banerjee D, Burton JO, Crowley L, Doulton T, Hameed MA, Hamer R, Menon M, Nicholas J, Ramakrishna SB, Shivakumar K, Geberhiwot T, Dasgupta I. Fabry disease in the haemodialysis population: outcome of a UK screening study (SoFAH). BMC Nephrol. 2025 May 26;26(1):259. doi: 10.1186/s12882-025-04127-x.