Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response: Relation to phenotype, storage cell markers, and therapeutic response

Nick Dekker, Laura van Dussen, Carla E. M. Hollak, Herman Overkleeft, Saskia Scheij, Karen Ghauharali, Mariëlle J. van Breemen, Maria J. Ferraz, Johanna E. M. Groener, Mario Maas, Frits A. Wijburg, Dave Speijer, Anna Tylki-Szymanska, Pramod K. Mistry, Rolf G. Boot, Johannes M. Aerts

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194 Citations (Scopus)


Gaucher disease, caused by a deficiency of the lysosomal enzyme glucocerebrosidase, leads to prominent glucosylceramide accumulation in lysosomes of tissue macrophages (Gaucher cells). Here we show glucosylsphingosine, the deacylated form of glucosylceramide, to be markedly increased in plasma of symptomatic nonneuronopathic (type 1) Gaucher patients (n = 64, median = 230.7 nM, range 15.6-1035.2 nM; normal (n = 28): median 1.3 nM, range 0.8-2.7 nM). The method developed for mass spectrometric quantification of plasma glucosylsphingosine is sensitive and robust. Plasma glucosylsphingosine levels correlate with established plasma markers of Gaucher cells, chitotriosidase (ρ = 0.66) and CCL18 (ρ = 0.40). Treatment of Gaucher disease patients by supplementing macrophages with mannose-receptor targeted recombinant glucocerebrosidase results in glucosylsphingosine reduction, similar to protein markers of Gaucher cells. Since macrophages prominently accumulate the lysoglycosphingolipid on glucocerebrosidase inactivation, Gaucher cells seem a major source of the elevated plasma glucosylsphingosine. Our findings show that plasma glucosylsphingosine can qualify as a biomarker for type 1 Gaucher disease, but that further investigations are warranted regarding its relationship with clinical manifestations of Gaucher disease
Original languageEnglish
Pages (from-to)e118-e127
Issue number16
Publication statusPublished - 20 Oct 2011

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