{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T19:41:32Z","timestamp":1781206892313,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T00:00:00Z","timestamp":1607817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GM1516C"],"award-info":[{"award-number":["01GM1516C"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Mass Spectrom"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative diseases predominantly in childhood that are characterized by psychomotor deterioration, epilepsy, and early death of patients. The NCLs analyzed in the present study are caused by defects of the specific enzymes, CLN1 (palmitoyl protein thioesterase 1; PPT1), CLN2 (tripeptidyl peptidase 1; TPP1), and CLN10 (cathepsin D). Specific and sensitive diagnostic assays of NCLs were the main goal of this study. They are of increasing importance, particularly since enzyme replacement therapy (ERT) for NCL2 has recently become available for clinical treatment, and ERTs for further NCLs are under development. Here, we report specific and sensitive determinations for CLN1, CLN2, and CLN10 on dried blood spots by tandem mass spectrometry using multiple reaction monitoring mass spectrometry (MRM\u2010MS). Identical substrates suitable for (i) fluorimetric determination of single enzymes and (ii) for MRM\u2010MS determination of multiple enzymes were synthesized by chemical coupling of alkyl\u2010umbelliferone building blocks with the corresponding peptidyl\u2010substrate groups recognized by the target enzyme. Enzymatic determinations were performed both by fluorimetry and MRM\u2010MS in patients with NCL1, NCL2, and NCL10 and showed good agreement in single assays. Moreover, duplex and triplex determinations were successfully performed for NCL1, NCL2, and NCL10. Specific peptidyl\u2010(4\u2010alkyl\u2010umbelliferone) substrates were also synthesized for mass spectrometric determinations of different cathepsins (cathepsins\u2010D, \u2010F, and \u2010B), to provide a differentiation of proteolytic specificities.<\/jats:p>","DOI":"10.1002\/jms.4675","type":"journal-article","created":{"date-parts":[[2020,12,13]],"date-time":"2020-12-13T18:23:30Z","timestamp":1607883810000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Enzymatic diagnosis of neuronal lipofuscinoses in dried blood spots using substrates for concomitant tandem mass spectrometry and fluorimetry"],"prefix":"10.1002","volume":"56","author":[{"given":"Stefan","family":"Maeser","sequence":"first","affiliation":[{"name":"Steinbeis Centre for Biopolymer Analysis and Biomedical Mass Spectrometry Mass Spectrometry Laboratory  Marktstrasse 29 Ruesselsheim am Main D\u201065428 Germany"},{"name":"Department of Chemistry Universit\u00e4t Konstanz  Konstanz 78457 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brindusa\u2010Alina","family":"Petre","sequence":"additional","affiliation":[{"name":"Steinbeis Centre for Biopolymer Analysis and Biomedical Mass Spectrometry Mass Spectrometry Laboratory  Marktstrasse 29 Ruesselsheim am Main D\u201065428 Germany"},{"name":"Department of Chemistry Universit\u00e4t Konstanz  Konstanz 78457 Germany"},{"name":"Department of Chemistry A.I. Cuza University of Iasi  Iasi Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Ion","sequence":"additional","affiliation":[{"name":"Steinbeis Centre for Biopolymer Analysis and Biomedical Mass Spectrometry Mass Spectrometry Laboratory  Marktstrasse 29 Ruesselsheim am Main D\u201065428 Germany"},{"name":"Department of Chemistry Universit\u00e4t Konstanz  Konstanz 78457 Germany"},{"name":"Department of Chemistry A.I. Cuza University of Iasi  Iasi Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Rawer","sequence":"additional","affiliation":[{"name":"Steinbeis Centre for Biopolymer Analysis and Biomedical Mass Spectrometry Mass Spectrometry Laboratory  Marktstrasse 29 Ruesselsheim am Main D\u201065428 Germany"},{"name":"Department of Chemistry Universit\u00e4t Konstanz  Konstanz 78457 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfried","family":"Kohlsch\u00fctter","sequence":"additional","affiliation":[{"name":"Children's Hospital University Medical Center Hamburg\u2010Eppendorf  Martinistrasse 52 Hamburg D\u201020246 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo M.","family":"Santorelli","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine IRCCS Foundation Stella Maris  I\u201056128 Calambrone Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Simonati","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine, Movement\u2010Neurology and Neuropathology Policlinico GB Rossi  P.le LA Scuro Verona I\u201037134 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Schulz","sequence":"additional","affiliation":[{"name":"Children's Hospital University Medical Center Hamburg\u2010Eppendorf  Martinistrasse 52 Hamburg D\u201020246 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2611-5389","authenticated-orcid":false,"given":"Michael","family":"Przybylski","sequence":"additional","affiliation":[{"name":"Steinbeis Centre for Biopolymer Analysis and Biomedical Mass Spectrometry Mass Spectrometry Laboratory  Marktstrasse 29 Ruesselsheim am Main D\u201065428 Germany"},{"name":"Department of Chemistry Universit\u00e4t Konstanz  Konstanz 78457 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.163"},{"key":"e_1_2_6_3_1","first-page":"2292","article-title":"Experimental therapies in the neuronal ceroid lipofuscinoses","volume":"1852","author":"Nevermann NJ","year":"2015","journal-title":"Biochem Biophys Acta"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.04.008"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.01.019"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-019-00620-8"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.06.018"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712649"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8111-6"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2004.035907"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac501994b"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.05.015"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2015.12.019"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2015.242560"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2016.256255"},{"key":"e_1_2_6_16_1","unstructured":"PrzybylskiM CozmaC MaeserS.Method for the diagnosis of lysosomal storage diseases. 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