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

2025/05/01 by Joerg Klepper · 1 voice · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Diet and metabolism studies #Metabolism and Genetic Disorders #Digestive system and related health

paper · doi:10.1002/jimd.70044

openalex publication_date 2025/05/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25

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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