Gaucher disease and Fabry disease: New markers and insights in pathophysiology for two distinct glycosphingolipidoses

Maria J. Ferraz, Wouter W. Kallemeijn, Mina Mirzaian, Daniela Herrera Moro, Andre Marques, Patrick Wisse, Rolf G. Boot, Lianne I. Willems, Herman S. Overkleeft, Johannes M F G Aerts

Research output: Contribution to journalArticlepeer-review


Gaucher disease (GD) and Fabry disease (FD) are two relatively common inherited glycosphingolipidoses caused by deficiencies in the lysosomal glycosidases glucocerebrosidase and alpha-galactosidase A, respectively. For both diseases enzyme supplementation is presently used as therapy. Cells and tissues of GD and FD patients are uniformly deficient in enzyme activity, but the two diseases markedly differ in cell types showing lysosomal accumulation of the glycosphingolipid substrates glucosylceramide and globotriaosylceramide, respectively. The clinical manifestation of Gaucher disease and Fabry disease is consequently entirely different and the response to enzyme therapy is only impressive in the case of GD patients. This review compares both glycosphingolipid storage disorders with respect to similarities and differences. Presented is an update on insights regarding pathophysiological mechanisms as well as recently available biochemical markers and diagnostic tools for both disorders. Special attention is paid to sphingoid bases of the primary storage lipids in both diseases. The value of elevated glucosylsphingosine in Gaucher disease and globotriaosylsphingosine in Fabry disease for diagnosis and monitoring of disease is discussed as well as the possible contribution of the sphingoid bases to (patho)physiology. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.

Original languageEnglish
Pages (from-to)811-825
Number of pages15
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number5
Publication statusPublished - May 2014


  • Activity-based probe
  • Fabry disease
  • Galactotriaosylsphingosine
  • Gaucher disease
  • Glycosphingolipid
  • Lysosome

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