{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T03:08:07Z","timestamp":1784776087681,"version":"3.55.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Sphingolipids play a crucial role in cellular functions and are essential components of cell membranes, signaling molecules, and lipid metabolism. In particular, ceramide is a key intermediate in sphingolipid metabolism and defects in ceramide metabolism can lead to various inborn errors of metabolism, making ceramides important targets for clinical screening and diagnosis. Detecting altered concentration patterns of sphingolipids is desirable for distinguishing related inborn errors of metabolism for diagnosis and treatment monitoring.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We developed a liquid chromatography-tandem mass spectrometry method with a pathway-oriented approach to focus on sphingolipids involved in ceramide metabolism. A total of 47 sphingolipids bearing different head groups and side chains were targeted. Precision\/reproducibility, linearity, and spike recovery extraction efficiency tests were performed on plasma and serum samples from confirmed cases of sphingolipidosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Linearity of the method showed the coefficient of determination (r2) for all standards to be &amp;gt;0.99 with a slope of 1.00 \u00b1 0.01. Intra- and interday reproducibility of standards spiked into plasma and serum revealed a coefficient of variation &amp;lt;20%. Spike and recovery assessment showed recovery values of 80%\u2013120% for all standards. Altered levels of sphingolipids from patients with hereditary sensory and autonomic neuropathy caused by pathogenic variants in SPTLC2 and hypomyelinating leukodystrophy related to variants in DEGS1 were detected, in agreement with trends reported in earlier studies confirming the utility of this pathway-centric method.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This method can serve as a useful tool to simultaneously monitor sphingolipids, enabling screening and diagnosis of inborn errors of ceramide metabolism.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvae115","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T12:20:25Z","timestamp":1724934025000},"page":"1366-1374","source":"Crossref","is-referenced-by-count":5,"title":["Development of a Multiplexed Sphingolipids Method for Diagnosis of Inborn Errors of Ceramide Metabolism"],"prefix":"10.1093","volume":"70","author":[{"given":"Seul Kee","family":"Byeon","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter Jared","family":"Wegwerth","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Zenka","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P","family":"George","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]},{"name":"Manipal Academy of Higher Education , Manipal, Karnataka ,","place":["India"]},{"name":"Institute of Bioinformatics, International Technology Park , Bangalore ,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6030-1903","authenticated-orcid":false,"given":"Filippo","family":"Pinto e Vairo","sequence":"additional","affiliation":[{"name":"Center for Individualized Medicine, Mayo Clinic , Rochester, MN","place":["United States"]},{"name":"Department of Clinical Genomics, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Oglesbee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"Matern","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9943-6127","authenticated-orcid":false,"given":"Akhilesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN ,","place":["United States"]},{"name":"Manipal Academy of Higher Education , Manipal, Karnataka ,","place":["India"]},{"name":"Center for Individualized Medicine, Mayo Clinic , Rochester, MN","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"2024110323573453300_hvae115-B1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/85817","article-title":"SPTLC1 is mutated in hereditary sensory neuropathy, type 1","volume":"27","author":"Bejaoui","year":"2001","journal-title":"Nat Genet"},{"key":"2024110323573453300_hvae115-B2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1194\/jlr.S091827","article-title":"A perilous path: the inborn errors of sphingolipid metabolism","volume":"60","author":"Dunn","year":"2019","journal-title":"J Lipid Res"},{"key":"2024110323573453300_hvae115-B3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-018-0025-4","article-title":"Lysosomal storage diseases","volume":"4","author":"Platt","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"2024110323573453300_hvae115-B4","doi-asserted-by":"crossref","first-page":"e1003536","DOI":"10.1371\/journal.pgen.1003536","article-title":"Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans","volume":"9","author":"Radner","year":"2013","journal-title":"PLoS Genet"},{"key":"2024110323573453300_hvae115-B5","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1002\/ana.24170","article-title":"Impairment of ceramide synthesis causes a novel progressive myoclonus epilepsy","volume":"76","author":"Vanni","year":"2014","journal-title":"Ann Neurol"},{"key":"2024110323573453300_hvae115-B6","doi-asserted-by":"crossref","first-page":"11144","DOI":"10.1016\/S0021-9258(19)49887-6","article-title":"Subcellular localization and membrane topology of serine palmitoyltransferase, 3-dehydrosphinganine reductase, and sphinganine N-acyltransferase in mouse liver","volume":"267","author":"Mandon","year":"1992","journal-title":"J Biol Chem"},{"key":"2024110323573453300_hvae115-B7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.jbior.2016.10.002","article-title":"Ceramidases, roles in sphingolipid metabolism and in health and disease","volume":"63","author":"Coant","year":"2017","journal-title":"Adv Biol Regul"},{"key":"2024110323573453300_hvae115-B8","doi-asserted-by":"crossref","first-page":"25001","DOI":"10.1074\/jbc.R600010200","article-title":"When do lasses (longevity assurance genes) become CerS (ceramide synthases)?: insights into the regulation of ceramide synthesis","volume":"281","author":"Pewzner-Jung","year":"2006","journal-title":"J Biol Chem"},{"key":"2024110323573453300_hvae115-B9","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nchembio.392","article-title":"An update on sphingosine-1-phosphate and other sphingolipid mediators","volume":"6","author":"Fyrst","year":"2010","journal-title":"Nat Chem Biol"},{"key":"2024110323573453300_hvae115-B10","doi-asserted-by":"crossref","first-page":"37118","DOI":"10.1074\/jbc.M502207200","article-title":"Sphk1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism","volume":"280","author":"Maceyka","year":"2005","journal-title":"J Biol Chem"},{"key":"2024110323573453300_hvae115-B11","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024110323573453300_hvae115-B12","doi-asserted-by":"crossref","first-page":"11178","DOI":"10.1074\/jbc.M109.092973","article-title":"Hereditary sensory neuropathy type 1 is caused by the accumulation of two neurotoxic sphingolipids","volume":"285","author":"Penno","year":"2010","journal-title":"J Biol Chem"},{"key":"2024110323573453300_hvae115-B13","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.bbalip.2018.12.013","article-title":"1-Deoxysphingolipids","volume":"1864","author":"Lone","year":"2019","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"2024110323573453300_hvae115-B14","doi-asserted-by":"crossref","first-page":"570628","DOI":"10.3389\/fendo.2020.570628","article-title":"Ceramides and ceramide scores: clinical applications for cardiometabolic risk stratification","volume":"11","author":"Hilvo","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2024110323573453300_hvae115-B15","doi-asserted-by":"crossref","first-page":"6149","DOI":"10.1038\/s41598-017-06604-2","article-title":"C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease","volume":"7","author":"Cozma","year":"2017","journal-title":"Sci Rep"},{"key":"2024110323573453300_hvae115-B16","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1038\/s41431-019-0444-z","article-title":"DEGS1 variant causes neurological disorder","volume":"27","author":"Dolgin","year":"2019","journal-title":"Eur J Hum Genet"},{"key":"2024110323573453300_hvae115-B17","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1056\/NEJMoa1815111","article-title":"Serine and lipid metabolism in macular disease and peripheral neuropathy","volume":"381","author":"Gantner","year":"2019","journal-title":"N Engl J Med"},{"key":"2024110323573453300_hvae115-B18","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1172\/JCI123959","article-title":"Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy","volume":"129","author":"Pant","year":"2019","journal-title":"J Clin Invest"},{"key":"2024110323573453300_hvae115-B19","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1021\/acs.jproteome.9b00640","article-title":"Skyline for small molecules: a unifying software package for quantitative metabolomics","volume":"19","author":"Adams","year":"2020","journal-title":"J Proteome Res"},{"key":"2024110323573453300_hvae115-B20","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/BF02215726","article-title":"Synthetic serum substitute (SSS): a globulin-enriched protein supplement for human embryo culture","volume":"12","author":"Weathersbee","year":"1995","journal-title":"J Assist Reprod Genet"},{"key":"2024110323573453300_hvae115-B21","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/hmg\/ddv611","article-title":"HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship","volume":"25","author":"Bode","year":"2016","journal-title":"Hum Mol Genet"},{"key":"2024110323573453300_hvae115-B22","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/85879","article-title":"Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I","volume":"27","author":"Dawkins","year":"2001","journal-title":"Nat Genet"},{"key":"2024110323573453300_hvae115-B23","doi-asserted-by":"crossref","first-page":"e365","DOI":"10.1212\/NXG.0000000000000365","article-title":"Deoxysphingolipids as candidate biomarkers for a novel SPTLC1 mutation associated with HSAN-I","volume":"5","author":"Boso","year":"2019","journal-title":"Neurol Genet"},{"key":"2024110323573453300_hvae115-B24","doi-asserted-by":"crossref","first-page":"100122","DOI":"10.1016\/j.jlr.2021.100122","article-title":"Metabolism of HSAN1- and T2DM-associated 1-deoxy-sphingolipids inhibits the migration of fibroblasts","volume":"62","author":"Karsai","year":"2021","journal-title":"J Lipid Res"},{"key":"2024110323573453300_hvae115-B25","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00125-011-2384-1","article-title":"Plasma deoxysphingolipids: a novel class of biomarkers for the metabolic syndrome?","volume":"55","author":"Othman","year":"2012","journal-title":"Diabetologia"},{"key":"2024110323573453300_hvae115-B26","doi-asserted-by":"crossref","first-page":"18559","DOI":"10.1074\/jbc.R900009200","article-title":"Desaturases: emerging models for understanding functional diversification of diiron-containing enzymes","volume":"284","author":"Shanklin","year":"2009","journal-title":"J Biol Chem"},{"key":"2024110323573453300_hvae115-B27","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1194\/jlr.P094433","article-title":"Rare DEGS1 variant significantly alters de novo ceramide synthesis pathway","volume":"60","author":"Blackburn","year":"2019","journal-title":"J Lipid Res"},{"key":"2024110323573453300_hvae115-B28","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1194\/jlr.M067033","article-title":"Elucidating the chemical structure of native 1-deoxysphingosine","volume":"57","author":"Steiner","year":"2016","journal-title":"J Lipid Res"},{"key":"2024110323573453300_hvae115-B29","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1074\/jbc.AC119.011883","article-title":"FADS3 is a Delta14Z sphingoid base desaturase that contributes to gender differences in the human plasma sphingolipidome","volume":"295","author":"Karsai","year":"2020","journal-title":"J Biol Chem"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/70\/11\/1366\/60330896\/hvae115.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/clinchem\/article-pdf\/70\/11\/1366\/60330896\/hvae115.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,3]],"date-time":"2024-11-03T23:57:47Z","timestamp":1730678267000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/70\/11\/1366\/7744957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":29,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,8,29]]},"published-print":{"date-parts":[[2024,11,4]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvae115","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,11]]},"published":{"date-parts":[[2024,8,29]]}}}