Dados do Trabalho

Título

SCREENING FABRY DISEASE IN WOMEN COMBINING ENZIME ACTIVITY WITH LYSO-GB3 - PARTIAL RESULTS OF A BRAZILIAN STUDY

Introdução

Fabry disease (FD) is a rare X-linked lysosomal storage disease that can affect multiple organs,
including the kidneys. The main objective of this study was to evaluate the effectiveness of a combination of α-
GAL enzyme activity and plasma levels of lyso-GL3 for screening FD in women with chronic kidney disease
(CKD).

Material e Método

Women with CKD, stages 3 to 5, in regular nephrological follow-up were selected from renal centers
in all regions of Brazil. Exclusion criteria: under 18 years old and 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 lyso-GL3 levels were above the reference range.
Sensitivity and specificity analyzes were performed to evaluate the performance of the combined biochemical
approach for the diagnosis of FD.

Resultados

From October 2020 to December 2022 1,647 collections were carried out. Low α-GAL activity was
found in 44 (2.6%) of the cases and increased lyso-GL3 was found in 101 (6.1%) of the cases. The mean age
was 53 [42 – 64] years. All cases of low α-GAL and/or increased lyso-GL3 were submitted to genetic analysis,
and 6 positive cases were found. As for genetic variants, four patients have R118C, one A143T and other with
T430G, all considered variants of uncertain significance (VUS). The sensitivity and specificity of α-GAL
reduction for the detection of FD was 83.3% and 97.6%, respectively. As for the increase in lyso-GL3, the
values were 16.6% and 93.9%, respectively. There were no cases that presented a concomitant increase in
lyso-GL3 and a reduction in enzymatic activity.

Discussão e Conclusões

Preliminary results suggest that the combination of α-GAL enzymatic activity with lyso-GL3
measurement may be a good alternative for screening FD in women with CKD. A thorough medical evaluation
is required to determine the pathogenicity of variants in these patients.

Palavras Chave

FABRY DISEASE, SCREENING, CKD