Lyso-Gb3 determination in classic and late onset Fabry patients

ROZENFELD, P.; CECI, ROMINA; VELAZCO A; VAENA E; CRIVARO, A.; MUCCI, J.; ORMAZABAL, M.; BONDAR, CONSTANZA

Simposio; 19th WORLD Symposium Lysosomal Disease Network; 2023

The α-galactosidase-A deficiency in Fabry disease (FD) causes progressive accumulation of globotriaosylceramide (Gb3) and its derivative globotriaosylsphingosine (LysoGb3). Recently, elevated serum levels of LysoGb3 were found in a group of FD patients. However, the utility of LysoGb3 for screening, severity or treatment follow-up is still controversial, and more data is needed. The aim of this work was to determine LysoGb3 concentrations in FD patients and normal controls, as well as in patients with benign or unknown significance variants on GLA gene. We recruited 205 adult patients, including controls, FD patients and patients with benign or unknown significance variants on GLA gene. Informed consent for collecting clinical data and blood samples for biobanking was obtained from all patients. FD patients were divided into 4 groups: late-onset females (n = 11), classic females (n = 21), late-onset males (n = 10), classic males (n = 21). 142 patients were on a specific treatment. LysoGb3 concentration was assayed in dried blood spots by HPLC-Tandem mass spectrometry. Comparisons between study groups were performed using the t-test. Our results showed that lysoGb3 values were higher in FD patients than controls. Overlap was found between late-onset patients and normal controls, with a rate of false negatives of 10 and 54% for males and females respectively. 20% of individuals with unknown significance variants displayed high values. Most of the patients on ERT have LysoGb3 not different from the naïve FD patients. LysoGb3 assay as a screening test has a sensitivity of 89%. The specificity of this assay was 98%, so a value above a cut-off needs confirmation by gold standard methods. Using LysoGb3 as a possible biomarker for follow-up of therapy did not show a good response among late-onset and females. LysoGb3 levels among classic males on ERT were lower than that of naïve patients, but no normalization was observed in any of the cases.