Development of a Multiplexed Sphingolipids Method for Diagnosis of Inborn Errors of Ceramide Metabolism.
Background 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...
| Publicado en: | Clinical Chemistry Vol. 70; no. 11; pp. 1366 - 1375 |
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| Autores principales: | , , , , , , , , , |
| Formato: | Journal Article |
| Publicado: |
Oxford University Press / USA
Nov2024
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=180860222&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 180860222 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00099147 10CS jtl: Clinical Chemistry issn: 00099147 maglogo: N pubinfo: dt: Nov2024 vid: 70 iid: 11 pid: 622 pub: Oxford University Press / USA artinfo: ui: 180860222 10.1093/clinchem/hvae115 180860222 ppf: 1366 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Development of a Multiplexed Sphingolipids Method for Diagnosis of Inborn Errors of Ceramide Metabolism. aug: au: Byeon, Seul Kee Kim, Jinyong Wegwerth, Peter Jared Zenka, Roman George, John P Vairo, Filippo Pinto e Oglesbee, Devin Schultz, Matthew J Matern, Dietrich Pandey, Akhilesh affil: Department of Laboratory Medicine and Pathology, Mayo Clinic , Rochester, MN , United States sug: ab: Background 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. Methods 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. Results Linearity of the method showed the coefficient of determination (r 2) for all standards to be >0.99 with a slope of 1.00 ± 0.01. Intra- and interday reproducibility of standards spiked into plasma and serum revealed a coefficient of variation <20%. Spike and recovery assessment showed recovery values of 80%–120% 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. Conclusions This method can serve as a useful tool to simultaneously monitor sphingolipids, enabling screening and diagnosis of inborn errors of ceramide metabolism. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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