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Publications

Journal Article Epublish

PubMed: 42638834 DOI: 10.1002/jmd2.70113

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

JIMD Rep 67(5):e70113

Authors: Lívia Maria Ferreira Sobrinho, Juliana Cristine Fontana, Claudia F Lorea, Helio van der Linden Júnior, Andréa C S Leite, Rayana Elias Maia, Lilia Farret, Carolina F Moura de Souza, Soraia Poloni, Fabiano O Poswar, Ida Vanessa D Schwartz, Fernanda Sperb-Ludwig

Affiliations

  • Postgraduate Program in Genetics and Molecular Biology Federal University of Rio Grande do Sul (UFRGS) Porto Alegre Rio Grande do Sul Brazil.
  • Department of Pediatrics, School of Medicine Federal University of Minas Gerais Belo Horizonte Minas Gerais Brazil.
  • Clinical Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil.
  • Dr. Henrique Santillo Rehabilitation Center Goiânia Goiás Brazil.
  • Neuro Kids Clinic Montes Claros Minas Gerais Brazil.
  • Department of Pediatrics and Genetics Federal University of Paraíba João Pessoa Paraíba Brazil.
  • Medical Genetics Service Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil.
  • Clinical Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil. Casa dos Raros Porto Alegre Rio Grande do Sul Brazil.
  • BRAIN Laboratory, Experimental Research Center Hospital de Clínicas de Porto Alegre Porto Alegre Rio Grande do Sul Brazil.
  • InRaras-Instituto Nacional de Ciência e Tecnologia Em Doenças Raras Porto Alegre Rio Grande do Sul Brazil.

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.

MeSH

Glucose Transport Proteins, Facilitative, Developmental Disabilities, Phenotype, Diet, Movement Disorders, Diet, Ketogenic, Movement