LysoGb3 quantification facilitates phenotypic categorization of Fabry disease patients: Insights gained by a novel MS/MS method
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
38906396
DOI
10.1016/j.cca.2024.119824
PII: S0009-8981(24)02076-X
Knihovny.cz E-zdroje
- Klíčová slova
- Diagnostics, Fabry disease, Globotriaosylsphingosine, Lysosomal storage, Mass spectrometry, Phenotype,
- MeSH
- alfa-galaktosidasa genetika metabolismus MeSH
- biologické markery krev MeSH
- chromatografie kapalinová MeSH
- dospělí MeSH
- Fabryho nemoc * krev diagnóza moč MeSH
- fenotyp MeSH
- glykolipidy krev moč MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- senioři MeSH
- sfingolipidy * krev MeSH
- tandemová hmotnostní spektrometrie * MeSH
- trihexosylceramidy metabolismus krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alfa-galaktosidasa MeSH
- biologické markery MeSH
- globotriaosyl lysosphingolipid MeSH Prohlížeč
- globotriaosylceramide MeSH Prohlížeč
- glykolipidy MeSH
- sfingolipidy * MeSH
- trihexosylceramidy MeSH
BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disease resulting from pathogenic variants in the GLA gene coding α-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' 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.
Citace poskytuje Crossref.org
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