GLOBOTRIAOSYLSPHINGOSINE (LYSO-GB3) DETERMINATION IN CLASSIC AND LATE ONSET FABRY PATIENTS

ROZENFELD, P.A.; CECI R.; BARRALES, F; VAENA, E; ORMAZABAL, M.; CRIVARO, A.; MUCCI, J.M.; BONDAR, C.

Congreso; Congreso Latinoamericano de Errores Innatos del Metabolismo y Pesquiza Neonatal; 2022

INTRODUCTION: Fabry disease (FD) (OMIM#301500) is an X-linked disease, resulting from the deficientactivity of the lysosomal enzyme α-galactosidase A (α-Gal A) [1,2]. The enzymatic defect causes theprogressive accumulation of globotriaosylceramide (Gb3) and its derivative globotriaosylsphingosine(LysoGb3). Both males and females suffer from Fabry disease, and two major phenotypes of Fabrydisease, classic and later-onset variants are observed. Recently, elevated serum levels of LysoGb3 werefound in a group of Fabry patients. However the utility of LysoGb3 for screening, severity or treatmentfollow-up is still controversial, and more data is needed. AIMS: To determine LysoGb3 concentrations inFabry patients and normal controls, as well as in patients with benign or unknown significance variantson GLA gene. METHODS: Informed consent for collecting clinical data and blood samples for biobankingwas obtained from all patients. We recruited 205 adult patients, including normal controls, Fabry patientsand patients with benign or unknown significance variants on GLA gene. Fabry patients were divided into4 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 bloodspots by HPLC-Tandem mass spectrometry. Comparisons between the study groups were performedusing the t-test. RESULTS: LysoGb3 values were higher in 4 groups of Fabry patients as compared tonormal controls. Overlap was found between late-onset patients and normal controls, with a rate of falsenegatives of 10 and 54% for males and females respectively. 20% of individuals with unknownsignificance variants displayed high values. Most of the patients on ERT have LysoGb3 not different fromthe naïve Fabry patients. CONCLUSIONS: 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 standardmethods. Using LysoGb3 as a possible biomarker for follow-up of therapy did not show a good responseamong late-onset and females. LysoGb3 levels among classic males on ERT were lower than that of naïvepatients, but no normalization was observed in any of the cases.