Glucose Transporter Deficiency Syndrome Type 1 (Glut1‐ DS ): New Insights From a Brazilian Cohort of Patients

Le résumé fourni par la source

ABSTRACT Glucose transporter deficiency syndrome type 1 (Glut1‐DS) is a rare neurometabolic disorder caused by pathogenic variants in SLC2A1 , characterized by epilepsy, neurodevelopmental delay, movement disorders, dysarthria, intellectual disability, and postnatal microcephaly. We aimed to characterize the natural history of a Brazilian cohort of patients with Glut1‐DS. Brazilian patients of all ages were included if they presented with clinical features consistent with Glut1‐DS and carried a pathogenic or likely pathogenic SLC2A1 variant. Forty patients were included (21 males; median age 9.1 years [IQR: 6.0–12.9]; median age at diagnosis 5.0 years [IQR: 3.0–9.9]), of whom 32 had the classical phenotype. The most frequent manifestations at inclusion were seizures (37/40), speech delay (34/40), and movement disorders (29/35). Thirty‐four patients (85%) were receiving ketogenic dietary therapy (27 classical ketogenic diet and 7 modified Atkins diet). Cerebrospinal fluid analysis was performed in 10 patients (27.5%), all of whom had hypoglycorrhachia. Genetic testing identified 31 distinct SLC2A1 variants, including 15 novel variants. Intrafamilial phenotypic variability was observed in one of four families with recurrent disease, and reduced penetrance was identified in one affected parent. Missense variants were generally associated with milder phenotypes than truncating variants. These findings expand the phenotypic and genotypic spectrum of Glut1‐DS, highlight the high proportion of previously unreported SLC2A1 variants in the Brazilian population, and reinforce the importance of comprehensive genetic evaluation and counseling for affected families.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.