Kidney Week

Abstract: FR-PO659

Fabry Disease Genetic Diagnosis in a Large CKD Population Tested with a Broad Kidney Gene Panel

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

• Westemeyer, Margaret, Natera, Inc., Austin, Texas, United States

Margaret Westemeyer, MS

• Deyo, Jennifer, Natera, Inc., Austin, Texas, United States

Jennifer Deyo, PharmD

• Warnock, David G., University of Alabama at Birmingham, Birmingham, Alabama, United States

David G. Warnock, MD

• Wallace, Eric L., University of Alabama at Birmingham, Birmingham, Alabama, United States

Eric L. Wallace, MD, FASN

Background

Fabry disease (FD) is a genetic disorder caused by variants in GLA that encode lysosomal enzyme α-galactosidase A and leads to progressive damage in various organs especially kidneys, heart, and brain, due to glycosphingolipid accumulation. Due to X-linked inheritance, FD is generally more severe in males. Females with FD exhibit heterogeneous presentation, are underdiagnosed and are expected to inherit the disease twice as often. Patients may undergo a diagnostic odyssey, with an estimate of at least 15 years between FD onset and diagnosis. Early diagnosis is key to preventing severe complications through initiation of multiple available FD treatments. We assessed the real-world prevalence and characteristics of FD detected by genetic testing in individuals with kidney disease.

Methods

Cases with a pathogenic (P) or likely pathogenic (LP) variant in GLA were identified in a large database of individuals that underwent genetic testing with a 385 renal gene panel (the Renasight^TM test, Natera, Inc.). Available clinical and demographic data including age, ethnicity, sex, and ICD-10 codes, were collected.

Results

Out of 67,437 cases, 111 (M:50; F:61) had a positive GLA finding, an overall prevalence of 1:608 (0.16%). The mean age of GLA-positive patients at the time of testing was 43.6y (M:44.4y; F:43.0y) and 47.8% were Caucasian. Of all GLA-positive cases, 47.7% had a clinical FD diagnosis, representing 58.0% and 39.3% of male and female patients, respectively. 9.9% (11/111) of GLA-positive cases had a second positive genetic finding, two of which had an a priori FD diagnosis. 72.7% (8/11) of cases with a second positive finding were female.

Conclusion

This study showed that broad genetic testing identified FD in kidney disease patients without a clinical diagnosis. The prevalence of FD among individuals with CKD, identified via genetic testing is significantly higher than the general population (1:40,000). The low proportion of female patients reporting FD suggests that diagnosis is less likely to be suspected in female patients with kidney disease. Furthermore, the high prevalence of dual positive findings in this cohort underscores the importance of testing with a broad genetic panel. Diagnosis of FD through genetic testing can inform the use of tailored therapeutics and diagnostic decisions.