Novel cerebrospinal fluid biomarkers of glucose transporter type 1 deficiency syndrome: Implications beyond the brain's energy deficit

Tessa M. A. Peters, Jona Merx, Pieter C. Kooijman, Marek Noga, Siebolt de Boer, Loes A. van Gemert, Guido Salden, Udo F. H. Engelke, Dirk J. Lefeber, Rianne E. van Outersterp, Giel Berden, Thomas Jan Boltje, Rafael Artuch, Leticia Pías, Ángeles García‐Cazorla, Ivo Barić, Beat Thöny, Jos Oomens, Jonathan Martens, Ron A. WeversMarcel M. Verbeek, Karlien L. M. Coene, Michèl A. A. P. Willemsen

Research output: Contribution to journalArticleAcademicpeer-review


We used next-generation metabolic screening to identify new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS), comparing metabolic cerebrospinal fluid (CSF) profiles from 12 patients to those of 116 controls. This confirmed decreased CSF glucose and lactate levels in patients with GLUT1DS and increased glutamine at group level. We identified three novel biomarkers significantly decreased in patients, namely gluconic + galactonic acid, xylose-α1-3-glucose, and xylose-α1-3-xylose-α1-3-glucose, of which the latter two have not previously been identified in body fluids. CSF concentrations of gluconic + galactonic acid may be reduced as these metabolites could serve as alternative substrates for the pentose phosphate pathway. Xylose-α1-3-glucose and xylose-α1-3-xylose-α1-3-glucose may originate from glycosylated proteins; their decreased levels are hypothetically the consequence of insufficient glucose, one of two substrates for O-glucosylation. Since many proteins are O-glucosylated, this deficiency may affect cellular processes and thus contribute to GLUT1DS pathophysiology. The novel CSF biomarkers have the potential to improve the biochemical diagnosis of GLUT1DS. Our findings imply that brain glucose deficiency in GLUT1DS may cause disruptions at the cellular level that go beyond energy metabolism, underlining the importance of developing treatment strategies that directly target cerebral glucose uptake.

Original languageEnglish
Pages (from-to)66-75
Number of pages10
JournalJournal of Inherited Metabolic Disease
Issue number1
Early online date10 Sept 2022
Publication statusPublished - Jan 2023
Externally publishedYes


  • O-glucosylation
  • SLC2A1
  • next-generation metabolic screening
  • oligosaccharides
  • untargeted metabolomics


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