Kidney Week

Abstract: SA-PO0147

Utility of Dried Blood Spot α-Galactosidase A Activity and Globotriaosylsphingosine Measurement for Fabry Disease Screening in Patients with Hemodialysis Across Hyogo Prefecture, Japan

Session Information

• Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Okamoto, Hayaki, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Hayaki Okamoto, MD

• Goto, Shunsuke, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Shunsuke Goto, MD, PhD

• Terada, Nanako, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Nanako Terada, MD

• Fujita, Mika, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Mika Fujita

• Sawada, Takaaki, Center for Clinical Genetics, Kumamoto University Hospital, Kumamoto, Japan

Takaaki Sawada, MD, PhD

• Nakamura, Kimitoshi, Department of Pediatrics, Graduate School of Life Sciences, Kumamoto University, Kumamoto, Japan

Kimitoshi Nakamura

• Oboshi, Wataru, Anges Clinical Research Laboratory, AnGes, Inc., Kawasaki, Kanagawa Prefecture, Japan

Wataru Oboshi, PhD

• Okuyama, Torayuki, Department of Clinical Genomics, Saitama Medical University, Moroyama-machi, Iruma-gun, Japan

Torayuki Okuyama, MD, PhD

• Nagano, China, Division of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

China Nagano, MD, PhD

• Nozu, Kandai, Division of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Kandai Nozu, MD, PhD

• Fujii, Hideki, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo Prefecture, Japan

Hideki Fujii, MD, PhD, FASN

Background

Fabry disease (FD) is an X-linked lysosomal disorder caused by pathogenic variants in the α-galactosidase A (GLA) gene. Hemodialysis patients are a high-risk population for FD. Although dried blood spot (DBS)-based GLA activity screening is widely used, false-negative results may occur, particularly in females and patients with late-onset FD retaining residual enzyme activity. Globotriaosylsphingosine (lyso-Gb3) is a disease-specific biomarker measurable from DBS samples, but its utility in large-scale screening remains unclear. We conducted a prefecture-wide FD screening program using DBS-based GLA activity and evaluated the additional utility of DBS lyso-Gb3 measurement.

Methods

From October 2022 to November 2025, adult hemodialysis patients from 87 facilities in Hyogo Prefecture, Japan, underwent FD screening using DBS-based GLA activity measurement. Low GLA activity was defined as <5.0 pmol/hr/disk in males and <7.0 pmol/hr/disk in females. Patients with low activity underwent repeat testing, and those with persistently low activity underwent GLA gene analysis. Lyso-Gb3 was measured using the same DBS samples, with levels ≥0.70 ng/mL considered elevated.

Results

Among 4,013 consenting patients, DBS GLA activity was measured in 3,832 patients. Mean age was 69.5 ± 11.8 years, and mean GLA activity was 20.4 ± 12.6 pmol/hr/disk. Low GLA activity was detected in 116 patients, of whom 30 showed persistently low activity on repeat testing. GLA pathogenic variants were identified in 3 patients (2 males and 1 female), corresponding to an FD prevalence of 0.08%.
Persistently elevated lyso-Gb3 levels were observed in 5 of the 116 patients with initially low GLA activity. FD was diagnosed in 3 of 30 patients (10.0%) with persistently low GLA activity and in 1 patient with elevated lyso-Gb3 levels. Two of the 5 patients with elevated lyso-Gb3 levels did not undergo genetic testing.

Conclusion

DBS-based lyso-Gb3 measurement may complement conventional GLA activity screening and improve the diagnostic yield of FD screening in hemodialysis patients. Further studies are needed to determine optimal cutoff values and validate combined DBS GLA activity and lyso-Gb3 screening strategies.

Acknowledgment

This research was supported by Japan Fabry Disease Forum Research Grant.

Funding

• Commercial Support – JCR Pharma