Fabry disease in the haemodialysis population: outcome of a UK screening study (SoFAH).

Background and hypothesis: 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.

Methods: 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 µmol/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.

Results: 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 µmol/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)).

Conclusions: Despite the implementation of stringent screening criteria, we did not identify any new confirmed cases of Fabry disease in this large UK haemodialysis population.