{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:26:17Z","timestamp":1787286377257,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/jcm15166419","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T14:07:34Z","timestamp":1787148454000},"page":"6419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucose Transporter Type 1 Deficiency Syndrome: Clinical Variability and Challenges in Ketogenic Diet Management in a Paediatric Case Series"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-9763","authenticated-orcid":false,"given":"Mariana","family":"Viegas","sequence":"first","affiliation":[{"name":"Inherited Metabolic Diseases Reference Centre, Coimbra Local Health Unit, MetabERN, 3004-561 Coimbra, Portugal"},{"name":"Oeste Local Health Unit, Pediatric Department, 2500-176 Caldas da Rainha, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanci","family":"Baptista","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Diseases Reference Centre, Coimbra Local Health Unit, MetabERN, 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F\u00e1tima","family":"Martins","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Diseases Reference Centre, Coimbra Local Health Unit, MetabERN, 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Almeida","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Diseases Reference Centre, Coimbra Local Health Unit, MetabERN, 3004-561 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Pereira","sequence":"additional","affiliation":[{"name":"Coimbra Local Health Unit, Department of Paediatric Neurology, Paediatric Hospital of Coimbra, 3000-602 Coimbra, Portugal"},{"name":"Refractory Epilepsy Reference Centre, Coimbra Local Health Unit, 3004-561 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9165-2159","authenticated-orcid":false,"given":"Filipa","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Neurodevelopment Unit, Aveiro Local Health Unit, Department of Paediatrics, 3814-501 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Salgado","sequence":"additional","affiliation":[{"name":"Coimbra Local Health Unit, Department of Medical Genetics, Paediatric Hospital of Coimbra, 3000-602 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Coimbra Local Health Unit, Department of Paediatric Neurology, Paediatric Hospital of Coimbra, 3000-602 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Diseases Reference Centre, Coimbra Local Health Unit, MetabERN, 3004-561 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6236-7926","authenticated-orcid":false,"given":"Rui","family":"Diogo","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Diseases Reference Centre, Coimbra Local Health Unit, MetabERN, 3004-561 Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.neuron.2015.03.035","article-title":"A cellular perspective on brain energy metabolism and functional imaging","volume":"86","author":"Magistretti","year":"2015","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1007\/s00424-020-02441-x","article-title":"Glucose transporters in brain in health and disease","volume":"472","author":"Koepsell","year":"2020","journal-title":"Pflug. 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