Falsaperla Raffaele, Sortino Vincenzo, Kluger Gerhard Josef, Herberhold Thomas, Rüegger Andrea, Striano Pasquale, Ruggieri Martino, Klepper Joerg, Ramantani Georgia
Neonatal Intensive Care Unit and Neonatal Accompaniment Unit, Azienda Ospedaliero-Universitaria Policlinico "Rodolico-San Marco," San Marco Hospital, University of Catania, Catania, Italy.
Unit of Pediatrics and Pediatric Emergency, Azienda Ospedaliero-Universitaria Policlinico "Rodolico-San Marco," San Marco Hospital, University of Catania, Catania, Italy.
Epilepsia Open. 2025 Feb;10(1):31-39. doi: 10.1002/epi4.13110. Epub 2024 Dec 6.
Glucose transporter type 1 deficiency syndrome (GLUT1DS) commonly presents with early-onset epilepsy that often resists conventional pharmacological treatment. Ketogenic diet therapy (KDT) is the preferred approach to address the underlying metabolic anomaly. However, a subset of GLUT1DS patients presents resistance to KDT, with the causes remaining elusive. This comprehensive literature review aims to explore the characteristics of KDT failure in GLUT1DS and identify risk factors within this population. Our goal is to improve counseling and prognostication for these patients. So, we conducted a comprehensive literature review on PubMed, focusing on studies documenting pediatric GLUT1DS patients with drug-resistant epilepsy unresponsive to KDT. We identified five cases of KDT failure in female GLUT1DS patients, aged 10 days to 13 years at diagnosis. Predominant seizure types were absence seizures, with a few cases of clonic, tonic, or myoclonic seizures. EEG consistently revealed 2-3.5 Hz generalized spike-and-wave discharges. Genetic investigations revealed point mutations and deletions in two cases each. Despite an in-depth search, no specific features were found to reliably distinguish KDT non-responders from responders, underscoring the need for further research. In cases of KDT ineffectiveness for seizure control in GLUT1DS patients, exploring alternative therapeutic strategies becomes imperative to managing symptoms while maintaining quality of life. Large-scale multicenter studies, facilitated through international collaborations like the European Network for Therapy in Rare Epilepsies (NETRE), hold promise in elucidating the complexities of this patient population and developing personalized therapeutic approaches. PLAIN LANGUAGE SUMMARY: Glucose transporter type 1 deficiency syndrome often causes difficult-to-treat epilepsy. The ketogenic diet works for many patients, but some do not respond. This review investigated cases of diet failure but could not identify common features among poor responders. Further research is needed to understand these cases and explore alternative treatments.
1型葡萄糖转运体缺乏综合征（GLUT1DS）通常表现为早发性癫痫，且常常对传统药物治疗耐药。生酮饮食疗法（KDT）是解决潜在代谢异常的首选方法。然而，一部分GLUT1DS患者对KDT耐药，其原因仍不清楚。这篇全面的文献综述旨在探讨GLUT1DS中KDT失败的特征，并确定该人群中的风险因素。我们的目标是改善对这些患者的咨询和预后评估。因此，我们在PubMed上进行了全面的文献综述，重点关注记录对KDT无反应的耐药性癫痫小儿GLUT1DS患者的研究。我们确定了5例KDT失败的女性GLUT1DS患者，诊断时年龄为10天至13岁。主要发作类型为失神发作，少数为阵挛性、强直性或肌阵挛性发作。脑电图始终显示2 - 3.5赫兹的广泛性棘慢波放电。基因研究发现两例各有一个点突变和缺失。尽管进行了深入搜索，但未发现能可靠区分KDT无反应者和有反应者的具体特征，这突出了进一步研究的必要性。对于GLUT1DS患者中KDT在控制癫痫发作方面无效的情况，探索替代治疗策略对于在维持生活质量的同时管理症状变得至关重要。通过欧洲罕见癫痫治疗网络（NETRE）等国际合作推动的大规模多中心研究，有望阐明这一患者群体的复杂性并制定个性化治疗方法。
1型葡萄糖转运体缺乏综合征常导致难以治疗的癫痫。生酮饮食对许多患者有效，但有些患者没有反应。本综述调查了饮食治疗失败的病例，但未能确定无反应者的共同特征。需要进一步研究以了解这些病例并探索替代治疗方法。
