Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics
Kearns-Sayre syndrome (KSS) is caused by duplications and/or deletions of mitochondrial DNA (mtDNA) and is typically diagnosed based on a classic triad of symptoms with chronic progressive external ophthalmoplegia (CPEO), retinitis pigmentosa, and onset before age 20 years. The present study aimed t...
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Veröffentlicht in: | Pediatric neurology 2023-06, Vol.143, p.68-76 |
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container_title | Pediatric neurology |
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creator | Salvador, Cathrin Lytomt Oppebøen, Mari Vassli, Anja Østeby Pfeiffer, Helle Cecilie Viekilde Varhaug, Kristin Nielsen Elgstøen, Katja Benedikte Prestø Yazdani, Mazyar |
description | Kearns-Sayre syndrome (KSS) is caused by duplications and/or deletions of mitochondrial DNA (mtDNA) and is typically diagnosed based on a classic triad of symptoms with chronic progressive external ophthalmoplegia (CPEO), retinitis pigmentosa, and onset before age 20 years. The present study aimed to diagnose two patients, on suspicion of KSS.
One of the patients went through a diagnostic odyssey, with normal results from several mtDNA analyses, both in blood and muscle, before the diagnosis was confirmed genetically.
Two patients presented increased tau protein and low 5-methyltetrahydrofolate (5-MTHF) levels in the cerebrospinal fluid (CSF). Untargeted metabolomics on CSF samples also showed an increase in the levels of free sialic acid and sphingomyelin C16:0 (d18:1/C16:0), compared with four control groups (patients with mitochondrial disorders, nonmitochondrial disorders, low 5-MTHF, or increased tau proteins).
It is the first time that elevated sphingomyelin C16:0 (d18:1/C16:0) and tau protein in KSS are reported. Using an untargeted metabolomics approach and standard laboratory methods, the study could shed new light on metabolism in KSS to better understand its complexity. In addition, the findings may suggest the combination of elevated free sialic acid, sphingomyelin C16:0 (d18:1/C16:0), and tau protein as well as low 5-MTHF as new biomarkers in the diagnostics of KSS. |
doi_str_mv | 10.1016/j.pediatrneurol.2023.02.016 |
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One of the patients went through a diagnostic odyssey, with normal results from several mtDNA analyses, both in blood and muscle, before the diagnosis was confirmed genetically.
Two patients presented increased tau protein and low 5-methyltetrahydrofolate (5-MTHF) levels in the cerebrospinal fluid (CSF). Untargeted metabolomics on CSF samples also showed an increase in the levels of free sialic acid and sphingomyelin C16:0 (d18:1/C16:0), compared with four control groups (patients with mitochondrial disorders, nonmitochondrial disorders, low 5-MTHF, or increased tau proteins).
It is the first time that elevated sphingomyelin C16:0 (d18:1/C16:0) and tau protein in KSS are reported. Using an untargeted metabolomics approach and standard laboratory methods, the study could shed new light on metabolism in KSS to better understand its complexity. In addition, the findings may suggest the combination of elevated free sialic acid, sphingomyelin C16:0 (d18:1/C16:0), and tau protein as well as low 5-MTHF as new biomarkers in the diagnostics of KSS.</description><identifier>ISSN: 0887-8994</identifier><identifier>EISSN: 1873-5150</identifier><identifier>DOI: 10.1016/j.pediatrneurol.2023.02.016</identifier><identifier>PMID: 37018879</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>5-Methyltetrahydrofolate ; Adult ; CAFSA ; DNA, Mitochondrial - genetics ; Humans ; Kearns-Sayre syndrome ; Kearns-Sayre Syndrome - diagnosis ; Kearns-Sayre Syndrome - genetics ; Metabolomics ; Mitochondrial DNA ; N-Acetylneuraminic Acid ; Sialic acid ; Sphingomyelin ; Sphingomyelins ; Tau protein ; tau Proteins ; Young Adult</subject><ispartof>Pediatric neurology, 2023-06, Vol.143, p.68-76</ispartof><rights>2023 The Author(s)</rights><rights>Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-f2b3868d46234770060d09149daeafd14395fd2f66318c54af6a7437b7f4d90e3</citedby><cites>FETCH-LOGICAL-c436t-f2b3868d46234770060d09149daeafd14395fd2f66318c54af6a7437b7f4d90e3</cites><orcidid>0000-0002-9187-3231 ; 0000-0003-4569-0968</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.pediatrneurol.2023.02.016$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37018879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Salvador, Cathrin Lytomt</creatorcontrib><creatorcontrib>Oppebøen, Mari</creatorcontrib><creatorcontrib>Vassli, Anja Østeby</creatorcontrib><creatorcontrib>Pfeiffer, Helle Cecilie Viekilde</creatorcontrib><creatorcontrib>Varhaug, Kristin Nielsen</creatorcontrib><creatorcontrib>Elgstøen, Katja Benedikte Prestø</creatorcontrib><creatorcontrib>Yazdani, Mazyar</creatorcontrib><title>Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics</title><title>Pediatric neurology</title><addtitle>Pediatr Neurol</addtitle><description>Kearns-Sayre syndrome (KSS) is caused by duplications and/or deletions of mitochondrial DNA (mtDNA) and is typically diagnosed based on a classic triad of symptoms with chronic progressive external ophthalmoplegia (CPEO), retinitis pigmentosa, and onset before age 20 years. The present study aimed to diagnose two patients, on suspicion of KSS.
One of the patients went through a diagnostic odyssey, with normal results from several mtDNA analyses, both in blood and muscle, before the diagnosis was confirmed genetically.
Two patients presented increased tau protein and low 5-methyltetrahydrofolate (5-MTHF) levels in the cerebrospinal fluid (CSF). Untargeted metabolomics on CSF samples also showed an increase in the levels of free sialic acid and sphingomyelin C16:0 (d18:1/C16:0), compared with four control groups (patients with mitochondrial disorders, nonmitochondrial disorders, low 5-MTHF, or increased tau proteins).
It is the first time that elevated sphingomyelin C16:0 (d18:1/C16:0) and tau protein in KSS are reported. Using an untargeted metabolomics approach and standard laboratory methods, the study could shed new light on metabolism in KSS to better understand its complexity. In addition, the findings may suggest the combination of elevated free sialic acid, sphingomyelin C16:0 (d18:1/C16:0), and tau protein as well as low 5-MTHF as new biomarkers in the diagnostics of KSS.</description><subject>5-Methyltetrahydrofolate</subject><subject>Adult</subject><subject>CAFSA</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Humans</subject><subject>Kearns-Sayre syndrome</subject><subject>Kearns-Sayre Syndrome - diagnosis</subject><subject>Kearns-Sayre Syndrome - genetics</subject><subject>Metabolomics</subject><subject>Mitochondrial DNA</subject><subject>N-Acetylneuraminic Acid</subject><subject>Sialic acid</subject><subject>Sphingomyelin</subject><subject>Sphingomyelins</subject><subject>Tau protein</subject><subject>tau Proteins</subject><subject>Young Adult</subject><issn>0887-8994</issn><issn>1873-5150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUc1u1DAQthCILoVXQJa4cEmwY8eO4VStulBR4LDs2XLsSfEqsYOdgPYNeGxcbUHixmmk-f408yH0ipKaEireHOsZnDdLCrCmONYNaVhNmrpgj9CGdpJVLW3JY7QhXSerTil-gZ7lfCSEtKrhT9EFk4QWTG3Qr5tgE5gMDu_nbz7cxekEow_YBId3CQDvvRm9xVfWO1z2W0jQp5hnH8yId-Na1nHAH8GkkKu9OaUiOQWX4gRv8Wf4iXc-uGKc8SGXgQ9hMekOlpL4CRbTxzFO3ubn6MlgxgwvHuYlOuyuv24_VLdf3t9sr24ry5lYqqHpWSc6x0XDuJSECOKIolw5A2ZwlDPVDq4ZhGC0sy03gzCSM9nLgTtFgF2i12ffOcXvK-RFTz5bGEcTIK5ZN1JJykUnWKG-O1NtuTcnGPSc_GTSSVOi76vQR_1PFfq-Ck0aXbCifvkQtPYTuL_aP78vhOszAcq5Pzwkna2HYItjArtoF_1_Bf0Gxo2j9A</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Salvador, Cathrin Lytomt</creator><creator>Oppebøen, Mari</creator><creator>Vassli, Anja Østeby</creator><creator>Pfeiffer, Helle Cecilie Viekilde</creator><creator>Varhaug, Kristin Nielsen</creator><creator>Elgstøen, Katja Benedikte Prestø</creator><creator>Yazdani, Mazyar</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9187-3231</orcidid><orcidid>https://orcid.org/0000-0003-4569-0968</orcidid></search><sort><creationdate>202306</creationdate><title>Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics</title><author>Salvador, Cathrin Lytomt ; Oppebøen, Mari ; Vassli, Anja Østeby ; Pfeiffer, Helle Cecilie Viekilde ; Varhaug, Kristin Nielsen ; Elgstøen, Katja Benedikte Prestø ; Yazdani, Mazyar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-f2b3868d46234770060d09149daeafd14395fd2f66318c54af6a7437b7f4d90e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>5-Methyltetrahydrofolate</topic><topic>Adult</topic><topic>CAFSA</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Humans</topic><topic>Kearns-Sayre syndrome</topic><topic>Kearns-Sayre Syndrome - diagnosis</topic><topic>Kearns-Sayre Syndrome - genetics</topic><topic>Metabolomics</topic><topic>Mitochondrial DNA</topic><topic>N-Acetylneuraminic Acid</topic><topic>Sialic acid</topic><topic>Sphingomyelin</topic><topic>Sphingomyelins</topic><topic>Tau protein</topic><topic>tau Proteins</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Salvador, Cathrin Lytomt</creatorcontrib><creatorcontrib>Oppebøen, Mari</creatorcontrib><creatorcontrib>Vassli, Anja Østeby</creatorcontrib><creatorcontrib>Pfeiffer, Helle Cecilie Viekilde</creatorcontrib><creatorcontrib>Varhaug, Kristin Nielsen</creatorcontrib><creatorcontrib>Elgstøen, Katja Benedikte Prestø</creatorcontrib><creatorcontrib>Yazdani, Mazyar</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Salvador, Cathrin Lytomt</au><au>Oppebøen, Mari</au><au>Vassli, Anja Østeby</au><au>Pfeiffer, Helle Cecilie Viekilde</au><au>Varhaug, Kristin Nielsen</au><au>Elgstøen, Katja Benedikte Prestø</au><au>Yazdani, Mazyar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics</atitle><jtitle>Pediatric neurology</jtitle><addtitle>Pediatr Neurol</addtitle><date>2023-06</date><risdate>2023</risdate><volume>143</volume><spage>68</spage><epage>76</epage><pages>68-76</pages><issn>0887-8994</issn><eissn>1873-5150</eissn><abstract>Kearns-Sayre syndrome (KSS) is caused by duplications and/or deletions of mitochondrial DNA (mtDNA) and is typically diagnosed based on a classic triad of symptoms with chronic progressive external ophthalmoplegia (CPEO), retinitis pigmentosa, and onset before age 20 years. The present study aimed to diagnose two patients, on suspicion of KSS.
One of the patients went through a diagnostic odyssey, with normal results from several mtDNA analyses, both in blood and muscle, before the diagnosis was confirmed genetically.
Two patients presented increased tau protein and low 5-methyltetrahydrofolate (5-MTHF) levels in the cerebrospinal fluid (CSF). Untargeted metabolomics on CSF samples also showed an increase in the levels of free sialic acid and sphingomyelin C16:0 (d18:1/C16:0), compared with four control groups (patients with mitochondrial disorders, nonmitochondrial disorders, low 5-MTHF, or increased tau proteins).
It is the first time that elevated sphingomyelin C16:0 (d18:1/C16:0) and tau protein in KSS are reported. Using an untargeted metabolomics approach and standard laboratory methods, the study could shed new light on metabolism in KSS to better understand its complexity. In addition, the findings may suggest the combination of elevated free sialic acid, sphingomyelin C16:0 (d18:1/C16:0), and tau protein as well as low 5-MTHF as new biomarkers in the diagnostics of KSS.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37018879</pmid><doi>10.1016/j.pediatrneurol.2023.02.016</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9187-3231</orcidid><orcidid>https://orcid.org/0000-0003-4569-0968</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 5-Methyltetrahydrofolate Adult CAFSA DNA, Mitochondrial - genetics Humans Kearns-Sayre syndrome Kearns-Sayre Syndrome - diagnosis Kearns-Sayre Syndrome - genetics Metabolomics Mitochondrial DNA N-Acetylneuraminic Acid Sialic acid Sphingomyelin Sphingomyelins Tau protein tau Proteins Young Adult |
title | Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics |
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