Klepper Joerg
Department of Pediatrics and Neuropediatrics, Childrens' Hospital Aschaffenburg, Aschaffenburg, Germany.
J Inherit Metab Dis. 2025 May;48(3):e70044. doi: 10.1002/jimd.70044.
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.
葡萄糖转运蛋白1缺乏综合征（Glut1DS）已成为一种可治疗但情况复杂的病症。如本综述所总结的，关于致病机制、表型、基因型和生酮饮食疗法（KDT）的资料越来越多。然而仍存在许多挑战：新症状不断出现且因年龄而异。在Glut1DS中，孕期的KDT以及新生儿和成人的临床特征尚不清楚。KDT对某些患者无效，原因不明。研究已超越了因GLUT1介导的葡萄糖跨血脑屏障转运受损而导致脑能量耗竭的概念。新的概念正在研究不同脑细胞类型的替代底物、转运机制和代谢相互作用。目前尚无法实现但未来可期的前景包括对Glut1DS进行新生儿筛查、找到可靠的生物标志物、预测预后以及除KDT之外的替代疗法。
