Abstract
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.