#2343 Fabry disease screening in patients with chronic kidney disease and dialysis at a single medical center in Taiwan

Abstract Background and Aims Chronic Kidney Disease (CKD) poses a significant global health challenge, with diverse contributing factors impacting its progression. Among these, Fabry Disease, a rare lysosomal storage disorder, has emerged as a potential complicating factor. Despite its relevance, the prevalence of Fabry Disease among CKD patients, particularly in Taiwan, remains insufficiently explored. Recognizing and understanding the occurrence of Fabry Disease in CKD populations are crucial for comprehensive patient care and may have implications for treatment strategies. Additionally, investigating the relationship between kidney function and Plasma α-Gal A activity is essential. α-Gal A, the enzyme deficient in Fabry Disease, may experience altered activity levels in the presence of compromised kidney function. Clarifying this connection is pivotal for gaining insights into the intricate interplay between Fabry Disease and CKD. This study aims to achieve three key objectives (1) Determine Fabry Disease Prevalence among CKD Patients in Taiwan.(2) Investigate the Impact of Kidney Function on Plasma α-Gal A Activity.(3) Characterize Gene Mutation Patterns and Demographic Data of Fabry Patients in CKD Population in Taiwan: Method Fabry Disease assessment involved a two-stage process, tailored to the patient's gender. Males underwent a dry blood test measuring α-galactosidase activity; samples below 15% of the adult average were deemed positive. Females were screened based on lyso-Gb3 levels in whole blood; a result exceeding 0.8 ng/ml was considered positive. Positive screenings prompted genomic DNA extraction, and the GLA gene's seven exons and intron 4 segment ([GRCh38/Hg38] chrX:101,399,610-101,399,874) were PCR-amplified. Sanger sequencing identified pathogenic variants. This gender-specific, multi-step approach ensures precision. Defined thresholds and advanced genomic techniques enhance diagnostic accuracy. The method provides a robust means of identifying Fabry Disease, supporting early intervention and personalized treatment. Results Study Recruitment: Initially, 2000 subjects enrolled, but 155 withdrew, yielding a final cohort of 1845 patients for analysis. Screening and Referral: Among 1602 subjects, 26 males (1.6%) were referred for DBS LysoGB3 check-up due to low serum α-Gal A activity. In a cohort of 243 females, 6 individuals (2.4%) underwent GLA genetic sequencing due to elevated lyso-GB3 levels. Clinical Presentation - Male Case: A male with acute stroke symptoms and CKD stage 3b (eGFR 34.5 mL/min/1.73 m²) showed significantly low DBS α-Gal A activity (0.48 μmol/hr) and elevated Plasma LysoGB3 (28.08 ng/ml).GLA genetic sequencing revealed a specific deletion (c.1072-1074delGAG, p. (Glu358 del)) in exon 7, leading to a Fabry disease diagnosis, classifying it as a specific type. The family pedigrees of this male patient are visually represented in Fig. 1, illustrating the genetic relationships within the family. Clinical Presentation - Female Case: A female on hemodialysis for four years, cause unknown, exhibited a DBS LysoGB3 level of 0.5 ng/ml. GLA genetic sequencing identified a nucleotide variation (c.640-801G>A) in intron 4, establishing a diagnosis of Fabry disease with the cardiac variant (301500). Fig. 2 demonstrates the relationship between serum DBS GLA activity and different stages of CKD. Our analysis reveals that in CKD stages 1, 2, 3 (3a and 3b), and 4, the serum GLA activity is significantly higher compared to stage 5. Conclusion The prevalence of Fabry Disease in our cohort was 0.1% (2 out of 1845 individuals), featuring one female with the cardiac variant and one male with the class type. Our investigation unveiled a significant rise in serum GLA activity in CKD stages 1–4 compared to stage 5, suggesting potential implications for early CKD detection. Moreover, serum α-Gal A activity displayed a notable correlation with age, BUN, and eGFR across CKD stages 1–5, questioning its status as a biomarker for advanced CKD and aging in CKD patients. This prompts consideration for a large-scale study to validate this hypothesis.