Increased Sphingomyelin and Free Sialic Acid in Cerebrospinal Fluid of Kearns-Sayre Syndrome: New Findings Using Untargeted Metabolomics.

Autor: Salvador CL; Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway. Electronic address: catsal@ous-hf.no., Oppebøen M; Department of Pediatrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Vassli AØ; Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Pfeiffer HCV; Department of Pediatrics, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Pediatrics, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark., Varhaug KN; The Mitochondrial Medicine and Neurogenetics (MMN) Group, Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Neurology, Haukeland University Hospital, Bergen, Norway., Elgstøen KBP; Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway., Yazdani M; Department of Medical Biochemistry, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Jazyk: angličtina
Zdroj: Pediatric neurology [Pediatr Neurol] 2023 Jun; Vol. 143, pp. 68-76. Date of Electronic Publication: 2023 Mar 04.
DOI: 10.1016/j.pediatrneurol.2023.02.016
Abstrakt: Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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