{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:19:27Z","timestamp":1791001167727,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T00:00:00Z","timestamp":1539561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,10,15]],"date-time":"2018-10-15T00:00:00Z","timestamp":1539561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Late infantile neuronal ceroid lipofuscinosis (<jats:italic>CLN2<\/jats:italic> disease) is a rare lysosomal storage disorder caused by a monogenetic deficiency of tripeptidyl peptidase-1 (TPP1). Despite knowledge that lipofuscin is the hallmark disease product, the relevant TPP1 substrate and its role in neuronal physiology\/pathology is unknown. We hypothesized that untargeted metabolite profiling of cerebrospinal fluid (CSF) could be used as an effective tool to identify disease-associated metabolic disruptions in <jats:italic>CLN2<\/jats:italic> disease, offering the potential to identify biomarkers that inform on disease severity and progression. Accordingly, a mass spectrometry-based untargeted metabolite profiling approach was employed to differentiate CSF from normal vs. <jats:italic>CLN2<\/jats:italic> deficient individuals. Of 1,433 metabolite features surveyed, 29 linearly correlated with currently employed disease severity scores. With tandem mass spectrometry 8 distinct metabolite identities were structurally confirmed based on retention time and fragmentation pattern matches, vs. standards. These putative <jats:italic>CLN2<\/jats:italic> biomarkers include 7 acetylated species \u2013 all attenuated in <jats:italic>CLN2<\/jats:italic> compared to controls. Because acetate is the major bioenergetic fuel for support of mitochondrial respiration, deficient acetylated species in CSF suggests a brain energy defect that may drive neurodegeneration. Targeted analysis of these metabolites in CSF of <jats:italic>CLN2<\/jats:italic> patients offers a powerful new approach for monitoring <jats:italic>CLN2<\/jats:italic> disease progression and response to therapy.<\/jats:p>","DOI":"10.1038\/s41598-018-33449-0","type":"journal-article","created":{"date-parts":[[2018,10,9]],"date-time":"2018-10-09T09:28:28Z","timestamp":1539077308000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease)"],"prefix":"10.1038","volume":"8","author":[{"given":"Miriam","family":"Sindelar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-488X","authenticated-orcid":false,"given":"Jonathan P.","family":"Dyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruba S.","family":"Deeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolan","family":"Sondhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Kaminsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry E.","family":"Kosofsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J.","family":"Ballon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S.","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,10,15]]},"reference":[{"key":"33449_CR1","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.bbamcr.2008.11.004","volume":"1793","author":"A Jalanko","year":"2009","unstructured":"Jalanko, A. & Braulke, T. 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