Global glycosphingolipid analysis in urine and plasma of female Fabry disease patients.
Biochim Biophys Acta Mol Basis Dis
; 1865(10): 2726-2735, 2019 10 01.
Article
em En
| MEDLINE
| ID: mdl-31319156
ABSTRACT
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase-A, which results in accumulation of the glycosphingolipid (GSL) globotriaosylceramide (Gb3). Gb3 and globotriaosylsphingosine (lyso-Gb3) levels in plasma and urine are used routinely for diagnosis and treatment monitoring. FD female patients are problematic to diagnose and to predict when to begin treatment. Further biomarkers are needed to detect pre-symptomatic females that will develop the chronic symptoms associated with FD. A LC-MS/MS glycosphingolipidomic assay was developed to measure lyso-Gb3 and GSLs from the lysosomal GSL degradation pathway, including globoside (Gb4), Gb3, ceramide dihexosides (CDH) and ceramide monohexosides (CMH). We analysed plasma and urine from a cohort of Fabry patients, grouped according to clinical symptoms and independent of treatment status (asymptomatic females nâ¯=â¯18, symptomatic females nâ¯=â¯18, males nâ¯=â¯27 and control urines nâ¯=â¯16 and control plasmas nâ¯=â¯58). Multivariate and subsequent univariate analysis showed urine GSLs which had highest significance in identifying asymptomatic females were total levels of CDH, in particular the long chain isoforms C221,C220,C221-OH,C220-OH,C242,C240,C242-OH,C241-OH,C240-OH,C260 which likely represent Galabiosylceramide (Ga2) and not lactosylceramide. These long chain Ga2 isoforms were found to be 5-fold elevated and more statistically significant (pâ¯<â¯0.0001) than plasma lyso-Gb3 (pâ¯<â¯0.01) in identifying asymptomatic Fabry female patients. Receiver operating characteristic curve analysis gave an area under the curve of 0.82 (pâ¯=â¯0.001) for lyso-Gb3 and 0.88 (pâ¯=â¯0.0006) for long-chain CDH isoforms indicating the long chain CDH isoforms were as, if not more, a better biomarker for the identification of female FD patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoesfingolipídeos
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Biomarcadores
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Doença de Fabry
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article