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Thesis May Be Reproduced, Stored Or Transmitted in Any Form Or by Any Means, Without Permission of the Author UvA-DARE (Digital Academic Repository) Detection of biomarkers for lysosomal storage disorders using novel technologies van Breemen, M.J. Publication date 2008 Document Version Final published version Link to publication Citation for published version (APA): van Breemen, M. J. (2008). Detection of biomarkers for lysosomal storage disorders using novel technologies. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:07 Oct 2021 versie 17-04.qxp 17-4-2008 10:47 Pagina 1 Detection of biomarkers for lysosomal storage disorders using novel technologies versie 17-04.qxp 17-4-2008 10:47 Pagina 2 Layout: Nick Dekker Coverdesign: Mikel Bitter Printed by Gildeprint Drukkerijen B.V., Enschede, the Netherlands Copyright © 2008 Mariëlle Jolanda van Breemen No part of this thesis may be reproduced, stored or transmitted in any form or by any means, without permission of the author. Financial support from Actelion, , and the J.E. Jurriaanse Stichting is gratefully acknowledged. The research described in this thesis was conducted at the Department of Medical Biochemistry in the Academic Medical Center of the University of Amsterdam under supervision of prof. dr. J.M.F.G. Aerts. versie 17-04.qxp 17-4-2008 10:47 Pagina 3 Detection of biomarkers for lysosomal storage disorders using novel technologies ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. D.C. van den Boom ten overstaan van een door het college voor promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op donderdag 12 juni 2008, te 10.00 uur door Mariëlle Jolanda van Breemen geboren te Hilversum versie 17-04.qxp 17-4-2008 10:47 Pagina 4 Promotiecommissie: PROMOTOR: Prof. dr. J.M.F.G. Aerts OVERIGE LEDEN: Prof. dr. T.M. Cox Prof. dr. R.A. Wevers Prof. dr. F.A. Wijburg Prof. dr. R.J.A. Wanders Dr. B. Bleijlevens Dr. D. Speijer Faculteit der Geneeskunde versie 17-04.qxp 17-4-2008 10:47 Pagina 5 versie 17-04.qxp 17-4-2008 10:47 Pagina 6 versie 17-04.qxp 17-4-2008 10:47 Pagina 7 Table of contents Prologue Chapter 1 Introduction 11 Section I: Biomarkers for Gaucher disease Chapter 2 Identification and use of biomarkers in Gaucher disease and other 35 lysosomal storage diseases Acta Paediatrica 94 (Suppl. 447) (2005) 43-46 Chapter 3 Marked elevation of the chemokine CCL18/PARC in Gaucher 43 disease: a novel surrogate marker for assessing therapeutic intervention Blood 103 (2004) 33-39 Chapter 4 Limitations in quantitation of the biomarker CCL18 in Gaucher 59 disease blood samples by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry Biochimica et Biophysica Acta 1764 (2006) 1626-1632 Chapter 5 Increased plasma macrophage inflammatory protein (MIP)-1α 71 and MIP-1β levels in type I Gaucher disease Biochimica et Biophysica Acta 1772 (2007) 788-796 Chapter 6 Correction in plasma macrophage inflammatory protein (MIP)-1β 89 is dose dependent during the initial phase of enzyme replacement therapy of type I Gaucher disease To be submitted as manuscript in shortened form Chapter 7 Siblings with Gaucher disease type III: differential outcome due 99 to timing of enzyme replacement and substrate reduction therapy Submitted Chapter 8 Potential artefacts in proteome analysis of plasma of Gaucher 111 patients due to protease abnormalities To be submitted with minor modifications Chapter 9 Assessing the statistical validity of proteomics based biomarkers 127 Analytica Chimica Acta 592 (2007) 210-217 versie 17-04.qxp 17-4-2008 10:47 Pagina 8 Chapter 10 Detection of mutant protein in complex biological samples: 143 glucocerebrosidase mutations in Gaucher disease Analytical Biochemistry 372 (2008) 52-61 Section II: Biomarkers for Fabry disease Chapter 11 The Dutch Fabry cohort: diversity of clinical manifestations and 161 Gb3 levels Journal of Inherited Metabolic Disease 30 (2007) 68-78 Chapter 12 Limited value of serum protein profiling for discrimination of 179 patients suffering from Fabry disease Submitted Epilogue Chapter 13 Biomarkers for lysosomal storage diseases: identification and 191 application as exemplified by chitotriosidase in Gaucher disease Acta Paediatrica 97 (Suppl. 457) (2008) 7-14 Addendum 1 Proteomic profiling of plasma and serum of elderly patients with 207 postoperative delirium Submitted Chapter 14 Summary and Discussion 221 Chapter 15 Samenvatting en Dankwoord 237 versie 17-04.qxp 17-4-2008 10:47 Pagina 9 versie 17-04.qxp 17-4-2008 10:47 Pagina 10 versie 17-04.qxp 17-4-2008 10:47 Pagina 11 ChapterChapter OneOne Introduction versie 17-04.qxp 17-4-2008 10:47 Pagina 12 12 versie 17-04.qxp 17-4-2008 10:47 Pagina 13 Introduction Introduction Lysosomal storage disorders Lysosomal storage disorders (LSDs) are inherited metabolic diseases characterized by impaired lysosomal function. Lysosomes are small single membrane-bounded organelles in eukaryotic cells, which are involved in the breakdown of intra- and extracellular biomolecules [1]. Lysosomes contain about 40 different hydrolytic enzymes. Each is responsible for breaking down particular substrates. Most LSDs are the result of a direct defect of one of these hydrolases, however, defects in enzyme co-activators, membrane transporters, targeting mechanisms for protein localization to the lysosome, or intracellular vesicular trafficking can also cause storage disorders [2]. When a lysosomal enzyme (or another type of protein important for its function) is absent or malfunctioning, macromolecules that are normally degraded will accumulate in the lysosome. This ultimately will lead to high concentrations of such macromolecules in the lysosomes of cells responsible for breakdown of these specific molecules. The accumulation of these macromolecules hampers lysosomal function and may result in impaired functioning of the cell as a whole. This eventually leads to progressive pathological dysfunction of tissues, their nature being depending on the type of disorder. Thus, all LSDs share a common pathogenesis: a genetic defect that leads to accumulation of substrates in lysosomes. The clinical manifestations, however, vary widely across the LSDs and sometimes even within a particular disease, depending on the genetic defect and the particular substrate stored. Over 70 distinct LSDs with an OMIM classification, and several other inherited disorders in the extended lysosomal apparatus are discerned today (see Table 1). The LSDs can be subdivided into several categories based on the type of defect and/or stored substrate product. Table 1. Lysosomal storage disorders and inherited defects in lysosome-like organelles. Sphingolipidoses Cer: ceramide, GlcCer: glucosylceramide, Gb3: globotriaosylceramide, gangliosides GM1 and GM2, SM: sphingomyelin Disease Eponyme OMIM Locus Gene Gene product Storage Farber Lipogranulomatosis 228000 8p22 Acid ceramidase Cer ASAH Fabry Anderson-Fabry 301500 Xq22 α-Galactosidase A Gb3 GLA Gaucher Glucosylceramidosis 606463 1q21 Glucocerebrosidase GlcCer 230900 GBA 231000 230800 GM1 gangliosidosis 230500 3p21 β-Galactosidase GM1 230600 GLB1 Tay-Sachs GM2-gangliosidosis B272800 15q23 β-Hexosaminidase α-subunit GM2 HEXA Sandhoff GM2-gangliosidosis O 268800 5q13 β-Hexosaminidase β-subunit GM2 HEXB 13 versie 17-04.qxp 17-4-2008 10:47 Pagina 14 Chapter 1 Table 1 continued Sphingolipidoses Cer: ceramide, GlcCer: glucosylceramide, Gb3: globotriaosylceramide, gangliosides GM1 and GM2, SM: sphingomyelin Disease Eponyme OMIM Locus Gene Gene product Storage Tay-Sachs GM2 ganglliosidosis 272750 5q32 GM2 activator protein GM2 AB variant AB GM2A Krabbe Globoid cell 245200 14q31 β-Galactosylceramidase GalCer leukodystrophy GALC Metachromatic Arylsulfatase A 250100 22q13 Arylsulfatase A Sulfatide leukodystrophy deficiency ARSA Prosaposin deficiency 176801 10q22 Prosaposin Multiple PSAP lipids Saposin B deficiency Metachromatic 249900 10q22 Saposin B Sulfatide leukodystrophy variant PSAP Saposin C deficiency Gaucher variant 610539 10q22 Saposin C GlcCer PSAP Niemann-Pick types 257200 11p15 Acid sphingomyelinase SM A and B SPMPD1 607616 Other lipidoses Disease Eponyme OMIM Locus Gene Gene product Storage Niemann-Pick type C1 257220 18q11 NPC1 Cholesterol, GSL NPC1 Niemann-Pick type C2 607625 14q24 NPC2 Cholesterol, GSL NPC2 Wolman Cholesteryl ester 278000 10q23.2 Acid lipase Cholesterol-ester storage disease LIPA Mucopolysaccharidoses (MPS) DS: dermatansulfate, HS: heparansulfate, KS: keratansulfate, CS: chrondoitinsulfate, HA: hyaluronan Disease Eponyme OMIM Locus Gene Gene product Storage MPS I Hurler 607015 4p16 α-Iduronidase DS , HS Hurler/Scheie (MPS 1H) IDUA Scheie 607015 (MPS 1HS) 607016 (MPS 1S) MPS II Hunter 309900 Xq28
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