Universiteit Leiden

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Analytical chemistry and biochemistry of glycosphingolipids: new developments and insights

Advanced mass spectrometry of glycosphingolipids takes the central stage in this thesis. Investigations focus on characterization of glycosphingolipid metabolism in health and disease with emphasis to the detection and accurate quantitation of known and so far unknown glycosphingolipids and closely regulated metabolites.

M. Mirzaian
14 juni 2017
Thesis in Leiden Repository

Inherited defects in lysosomal degradation of glycosphingolipids, in particular the glycosphingolipidoses Gaucher disease (GD) and Fabry disease (FD), relatively common lysosomal storage disorders, are key topics of examination. The thesis provides an introductory background on the field of research and contains three different sections describing conducted experimental work. Section one consists of studies reporting on the discovery of excessive occurrence of glycosphingoid bases in lysosomal storage diseases, the development of methods for their accurate quantitation in biological samples with UPLC-ESI-MS/MS and the use of these methods in diagnosis and disease monitoring. The great value of identical 13C-encoded (glyco)sphingolipids and their bases as internal standards in mass spectrometric quantitation of these lipids in biological materials is described. Section two introduces clinical aspects and challenges of GD and FD and provides examples of the practical value of lipid analyses in the GD and FD clinic. Section three concerns the pathophysiology of lysosomal disorders in glycosphingolipid metabolism and related fundamental investigations.