journal article Open Access May 01, 2025

Glut1 Deficiency Syndrome: Novel Pathomechanisms, Current Concepts, and Challenges

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Abstract
ABSTRACT
Glut1 Deficiency Syndrome (Glut1DS) has emerged as a treatable, but complex entity. Increasing data on pathogenic mechanisms, phenotype, genotype, and ketogenic dietary therapies (KDT) are available, as summarized in this review. Many challenges remain: novel symptoms emerge and vary with age. In Glut1DS, KDT in pregnancy and the clinical features in neonates and adults are poorly understood. KDT are ineffective in some patients for reasons yet unknown. Research reaches beyond the concept of brain energy depletion by impaired GLUT1‐mediated glucose transfer across the blood–brain barrier. Novel concepts investigate alternative substrates, transport mechanisms, and metabolic interactions of different brain cell types. Future, yet currently unavailable prospects are neonatal screening for Glut1DS, reliable biomarkers, predictors for outcome, and alternative therapies, along with and beyond KDT.
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Details
Published
May 01, 2025
Vol/Issue
48(3)
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Cite This Article
Joerg Klepper (2025). Glut1 Deficiency Syndrome: Novel Pathomechanisms, Current Concepts, and Challenges. Journal of Inherited Metabolic Disease, 48(3). https://doi.org/10.1002/jimd.70044