Rare presentations of GLUT1 deficiency syndrome: Rare variants with cortical dysplasia in twounrelated families

Abstract

Glucose transporter type 1 deficiency syndrome (GLUT1DS) affects all age groups, from infants to adolescents, and involves age-specific symptoms. Nonclassic GLUT1 DS is observed in 10% of cases, in which seizures are not observed, and the condition involves a milder accompanying phenotype and paroxysmal dyskinesias. Cranial imaging findings in cases of GLUT1 DS are variable. The purpose of this report is to describe rare genetic variants in two cases of GLUT1 DS with cortical dysplasia detected at magnetic resonance imaging (MRI) and exhibiting differing clinical presentations and to discuss the relationship between them. Two cases presenting to the Bal & imath;kesir University Medical Faculty paediatric neurology clinic, T & uuml;rkiye, between 01.08.2019 and 01.12.2024 due to seizures and inability to speak/numbness in the hands and arms, diagnosed as GLUT1 DS, and with cortical dysplasia, were included. The patients' files, MRI and physical examination findings and family pedigrees were evaluated. We detected two different pathogenic and likely pathogenic variants in SLC2A1 (NM_006516.3) in patients from unrelated families. Patient 1 exhibited a heterozygous c. 1208C > T variant and patient 2 a heterozygous likely c. 278G > A variant. In conclusion, the careful evaluation of patients with structural brain damage and determination of the molecular aetiology of underlying inherited metabolic diseases are highly important in terms of the provision of treatment, prognosis, and genetic counselling. Although cortical malformations have been reported in patients with GLUT1 DS, the mechanism involved remains unclear, and this report highlights the potential relationship between cortical dysplasia and specific genotypes in GLUT1 DS. Further prospective observational and functional studies involving larger numbers of cases and centres are now needed.