Partial Results of a Brazilian Study Evaluating an Alternative Method for Fabry Disease Screening in Women

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Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder that may affect multiple organs, including the kidneys. The main objective of this study was to evaluate the effectiveness of combining α-GAL enzyme activity and plasma levels of lyso-GL3 for screening FD in females with chronic kidney disease (CKD). Methods: Female with CKD, stages 3 to 5, under regular nephrology follow up were selected from renal centers of all regions of Brazil. Exclusion criteria: under 18 years old and a known diagnosis of FD. Patients underwent biochemical analysis of α-GAL enzyme activity and plasma levels of lyso-GL3. GLA gene sequencing was performed if α-GAL enzyme activity was below and/or the lyso-GL3 levels were above the reference range. Sensitivity and specificity analyses were performed to assess the performance of the combined biochemical approach for the diagnosis of FD. Results: From October 2020 to December 2021, 1163 patients were included. Low α-GAL activity was found in 36 (3.1%) patients and increased lyso-GL3 levels were found in 95 (8.2%) patients. The median age was 52 [42 - 63] years. Genetic analysis of the patients who presented low α-GAL and/or increased lyso-GL3 detected the same genetic variant of unknown significance in the GLA gene, R118C, in 3 unrelated patients. The sensitivity and specificity of α-GAL reduction for the detection of FD was 97% and 66%, respectively. Whereas for high plasma levels of lyso-GL3, they were 91% and 33%, respectively. No cases presented concomitantly increased lyso-GL3 and reduced enzyme activity. Conclusions: Preliminary results suggest that combining α-GAL enzymatic activity with lyso-GL3 dosage may be a good alternative for screening FD in females with CKD. A thorough medical evaluation is required to determine the pathogenicity of R118C in our patients.

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