Joana Ribeiro

Background/Objectives: Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare neurometabolic disorder caused by pathogenic variants in the SLC2A1 and a treatable cause of epilepsy and movement disorders. We aimed to describe clinical variability, diagnostic pathways and treatment outcomes in a paediatric case series, with a focus on ketogenic diet management. Methods: We retrospectively reviewed five paediatric patients with genetically confirmed glucose transporter type 1 deficiency syndrome followed at a tertiary center. Clinical presentation, biochemical findings, genetic results, treatment, dietary adherence and outcomes were analyzed. Results: Patients presented with development delay (4/5), movement disorders (4/5) and seizures (2/5), with symptom onset between 4 and 14 months. Diagnosis occurred between 22 and 54 months. Pathogenic SLC2A1 variants were identified in all patients, de novo in three cases. Hypoglycorrhachia was documented in two patients. All patients were treated with a classical ketogenic diet (ratio 1:1 to 3:1). Clinical improvement was observed in four patients, including better seizure control and motor function, although ketone levels were frequently suboptimal. Treatment duration ranged from two to 17 years. Long-term adherence and dietary implementation represented major challenges. Conclusions: Glucose transporter type 1 deficiency syndrome shows marked clinical heterogeneity, which may delay diagnosis. The ketogenic diet is effective in improving seizure control and neurological outcomes, although long-term adherence remains a major challenge. This case series highlights practical difficulties in diagnosis and dietary management in real-world clinical settings.