Glucose transporter type 1 deficiency syndrome: Phenotypes, molecular findings, and ketogenic therapy implementation...

Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare metabolic encephalopathy caused by pathogenic SLC2A1 variants. Ketogenic dietary therapy (KDT) is the mainstay of treatment. In Latin America, Glut1DS remains underdiagnosed due to limited awareness and restricted access to genetic testing. This study describes the clinical and genetic features, management, and response to KDT in an Argentine cohort.

A retrospective multicenter study was conducted including patients with a clinical and/or genetic diagnosis of Glut1DS. Clinical data, seizure types, neurodevelopmental features, treatment response, and KDT characteristics were collected from medical records using a standardized form. Genetic confirmation was obtained by SLC2A1 sequencing. Descriptive and comparative analyses were performed.

Thirty-nine patients with Glut1DS (64% males) were included. Mean age at evaluation was 13.7 years. Median ages at symptom onset and diagnosis were 6 and 55 months, respectively, with a median diagnostic delay of 49 months. Cognitive impairment was present in two-thirds of patients, and movement disorders in 79%. Epilepsy occurred in 74%. Of 39 patients, all but one received KDT, with MCT oil in 64%. Thirty patients remained on KDT, achieving seizure freedom in 86% and >50% reduction in four others. Improvements were reported in motor coordination (38%), cognition and attention (10%), energy (10%), and behavior (8%). No major adverse effects were reported.

This first national report underscores the clinical diversity of Glut1DS in Argentina and a positive trend toward earlier KDT initiation. Strengthening early diagnosis, systematic follow-up, and equitable access to therapy remains essential.