Glucose transporter type 1 deficiency syndrome 2025 Guidelines

1. Glucose Transporter Type 1
Deficiency Syndrome (Glut1DS):
Diagnosis & Management
Based on 2025 Guidelines
Presented by: [Your Name], Expert in
Neurometabolic Disorders

2. Introduction
• - Rare, treatable neurometabolic disorder
• - Caused by mutations in SLC2A1 (Glut1)
• - Impaired brain glucose transport → cerebral
energy deficiency
• - Autosomal dominant; mostly de novo
• - Described by De Vivo (1991)

3. Clinical Features Overview
• - Early-onset seizures (1–6 months)
• - Movement disorders (e.g., PED, ataxia,
dystonia)
• - Developmental and cognitive delay
• - Microcephaly, craniofacial anomalies
• - Atypical: migraines, hemiparesis, anemia

4. Epilepsy
• - ~90% have seizures, often first symptom
• - Types: tonic-clonic, absence, myoclonic-
atonic
• - Typically drug-resistant
• - Responsive to ketogenic diet therapy (KDT)

5. Movement Disorders
• - Eye-head movements in infancy
• - Ataxia, dystonia, chorea, tremor
• - Paroxysmal dyskinesias (exercise/fasting
triggered)
• - Worsened by stress, illness

6. Developmental & Cognitive
Impairment
• - Speech and motor delays
• - Visual-spatial, executive dysfunction
• - Intellectual disability (mild–severe)

7. Pathophysiology
• - Glut1 enables glucose transport at BBB
• - SLC2A1 mutation → haploinsufficiency
• - Leads to cerebral energy failure
• - Impairs angiogenesis, glycolysis, glycosylation

8. Diagnostic Approach
• - Suspect in early epilepsy + movement
disorders
• - CSF glucose <2.2 mmol/L; ratio <0.4
• - Normal/low CSF lactate
• - EEG, MRI, PET, MRS support

9. Genetic & Functional Testing
• - 80–90%: SLC2A1 mutations
• - 3-OMG uptake ↓ in RBCs
• - METAglut1 test: high specificity
• - Some SLC2A1-negative but classic Glut1DS

10. Differential Diagnosis
• - Hypoglycorrhachia causes (infection, HK1
variants)
• - Mitochondrial disorders (high lactate)
• - Epileptic encephalopathies
• - Paroxysmal movement disorders

11. Management - Ketogenic Diet
Therapy
• - Main treatment
• - High-fat, low-carb diet → ketones
• - Early start = better outcomes
• - Improves seizures, motor, cognition

12. Other Therapies
• - ASMs: limited use
• - Triheptanoin: limited benefit
• - Experimental: sodium lactate, lipoic acid
• - Acetazolamide: may reduce seizures

13. Long-Term Management &
Prognosis
• - Monitor growth, renal, cardiovascular health
• - Plan transition to adult care
• - KDT safety/duration under study
• - Early intervention = better QoL

14. Future Directions
• - Expand newborn screening
• - Research SLC2A1-negative cases
• - Alternative fuels, protein/gene therapy
• - Exosomes, new small molecules

15. Conclusion
• - Treatable if diagnosed early
• - KDT is cornerstone
• - Multidisciplinary care vital
• - Promising future research

16. References & Acknowledgements
• - Based on: World J Pediatr (2025) 21:149–158
• - Thanks: Chinese Epilepsy Association,
contributors