Clinical and genetic characteristics of glucose transporter 1 deficiency syndrome in a large cohort of Chinese patients

Background Mutations in the SLC2A1 gene cause glucose transporter type 1 deficiency syndrome (Glut1DS). This study aimed to investigate the clinical and molecular genetics characteristics of Chinese patients with Glut1DS. Methods The clinical data of patients with Glut1DS were analyzed retrospectively. SLC2A1 mutation analysis was performed using Sanger sequencing or next-generation sequencing (NGS). Multiplex ligation-dependent probe amplification (MLPA) was conducted in patients with negative results. Results A total of 90 patients were diagnosed with Glut1DS, including 63 (70%) classic type and 27 (30%) non-classic type. Seizures occurred in 69 patients (77%), movement disorders were observed in 58 (68%), and episodic eye-head movements were noted in 17 (19%). Cerebrospinal fluid (CSF) glucose levels were available for 73 patients (81%), ranging from 1.0 to 2.6 mmol/L (median 1.9 mmol/L), with 90% (66/73) of patients showing levels below 2.2 mmol/L. Additionally, CSF-to-blood glucose ratios measured in 71 patients (79%) ranged from 0.20 to 0.63 (median 0.37), with 87% (62/71) of patients having ratios below 0.45. Genetic analysis identified 69 variants of the SLC2A1 gene including 39 previously reported and 30 unreported variants. The two most common variants were c.997C > T (p.Arg333Trp) and c.988C > T (p.Arg330*). Following ketogenic diet therapy, seizures were controlled in 47 of 57 patients (82%), movement disorders resolved in 18 of 47 patients (38%), and improved in 26 of 47 patients (55%). Conclusions The clinical manifestations of Glut1DS primarily include seizures, movement disorders, and developmental delay. Most affected children had CSF glucose levels below 2.2 mmol/L, with CSF-to-blood glucose ratios under 0.45. Two of the most common SLC2A1 variants were identified in our cohort. Ketogenic diet therapy was effective in controlling seizures, improving movement disorders, and was well tolerated.