Abstract: FR-PO673
Screening for Fabry Disease in Haemodialysis Population (SoFAH) Study
Session Information
- Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Ng, Khai Ping, University Hospitals of Derby and Burton NHS Foundation Trust, Derby, United Kingdom
- Sandhu, Manjinder Kaur, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, United Kingdom
- Geberhiwot, Tarekegn, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, United Kingdom
- Dasgupta, Indranil, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Birmingham, United Kingdom
Background
Fabry disease is an X-linked inherited lysosomal storage disorder with an estimated prevalence amongst end-stage kidney disease (ESRD) population of 0.3% in men and 0.1% in women. Due to its non-specific manifestations, Fabry disease especially the later-onset variant, is often under-diagnosed. We aimed to estimate its prevalence in a large haemodialysis (HD) population in the UK.
Methods
SoFAH is a cross-sectional, multi-centre screening study. All adult HD patients at 8 renal units in the Midlands, UK were invited to the study. All male participants are tested using dried blood spot alfa-galactosidase enzyme and Lyso-Gb3 assay. If either the enzyme (≤2.8 µmol/L/H) or Lyso-Gb3 (≥ 3.5 ng/mL) level was abnormal, genetic testing for GLA mutation was performed. All females had alfa-galactosidase enzyme, Lyso-GB3 and genetic tests. We also performed symptoms' survey. The study was approved by the UK Health Research Authority.
Results
Of the 2,452 HD patients, 1323 consented to the study. Their mean age was 68 (SD 15) year-old, 67% male, 64% white ethnicity, dialysis vintage of 2.6 (IQR 8.1) months and 32% had renal biopsy. Diabetic nephropathy (28%) was the most common cause of ESRD. 21% had no known cause of ESRD and 9% had hypertensive/ischaemic nephropathy. Majority had cardiovascular disease (85%), including 10% with heart failure. 27% self-reported burning pain in extremities, 25% heat intolerance, 25% gastrointestinal symptoms without a cause, 22% family history of renal disease and 41% family history of heart disease or stroke. Overall, 216 (16%, 156 male) had low enzyme level but all had normal Lyso-Gb3 level. Only 3 (0.2%) had abnormal Lyso-Gb3 but all had normal enzyme level. One female participant with normal enzyme and Lyso-Gb3 levels but GLA variant, heterozygous c.937G>T (p.(Asp313Tyr), which was deemed to be non-pathogenic variant.
Conclusion
Despite implementing stringent screening in both male and female to avoid false negative, we did not identify any new cases of Fabry disease in 1,323 HD patients. This finding suggested lower prevalence of Fabry disease than previously reported but might also be influenced by our cohort's demography and older age. Symptoms commonly associated with Fabry disease were non-specific and self-reported in almost a quarter of the participants.
Funding
- Commercial Support – Sanofi-Genzyme