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LysoGb3 quantification facilitates phenotypic categorization of Fabry disease patients: Insights gained by a novel MS/MS method

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10483695" target="_blank" >RIV/00216208:11110/24:10483695 - isvavai.cz</a>

  • Alternative codes found

    RIV/00064165:_____/24:10483695

  • Result on the web

    <a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VEJM6VDdvZ" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=VEJM6VDdvZ</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.cca.2024.119824" target="_blank" >10.1016/j.cca.2024.119824</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    LysoGb3 quantification facilitates phenotypic categorization of Fabry disease patients: Insights gained by a novel MS/MS method

  • Original language description

    Background: Fabry disease (FD) is an X-linked lysosomal storage disease resulting from pathogenic variants in the GLA gene coding alpha-galactosidase A (AGAL) and cleaving terminal alpha-linked galactose. Globotriaosylceramide (Gb3) is the predominantly accumulated sphingolipid. Gb3, deacylated-Gb3 (lysoGb3), and methylated-Gb3 (metGb3) have been suggested as FD biomarkers. Materials and Methods: We developed a novel LC-MS/MS method for assessing lysoGb3 levels in plasma and Gb3 and metGb3 in urine and tested 62 FD patients, 34 patients with GLA variants of unknown significance (VUS) and 59 healthy controls. AGAL activity in white blood cells (WBCs) and plasma was evaluated in parallel. Results: In males, lysoGb3 concentrations in plasma separated classic and late-onset FD patients from each other and from individuals carrying GLA VUS and healthy controls. Calculating AGAL activity/plasmatic lysoGb3 ratio allowed to correctly categorize all females with classic and majority of patients with late-onset FD phenotypes. Correlation of AGAL activity in WBCS with lipid biomarkers identified threshold activity values under which the biomarkers&apos; concentrations increase. Conclusion: We developed a novel simplified LC-MS/MS method for quantitation of plasma lysoGb3. AGAL activity/plasma lysoGb3 ratio was identified as the best predictor for FD. AGAL activity correlated with plasma lysoGb3 and corresponded to individual FD phenotypes.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • OECD FORD branch

    30101 - Human genetics

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Others

  • Publication year

    2024

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Clinica Chimica Acta

  • ISSN

    0009-8981

  • e-ISSN

    1873-3492

  • Volume of the periodical

    561

  • Issue of the periodical within the volume

    July

  • Country of publishing house

    NL - THE KINGDOM OF THE NETHERLANDS

  • Number of pages

    10

  • Pages from-to

    119824

  • UT code for WoS article

    001291643700001

  • EID of the result in the Scopus database

    2-s2.0-85196486102