Clinical and genetic analysis of children with glucose transporter type 1 deficiency syndrome

Abstract

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare metabolic encephalopathy with a wide variety of clinical phenotypes. In the present study, 15 patients diagnosed with GLUT1-DS were selected, all of whom had obvious clinical manifestations and complete genetic testing. Their clinical data and genetic reports were collated. All patients were provided with a ketogenic diet (KD) and an improvement in their symptoms was observed during a follow-up period of up to 1 year. The results revealed that the 15 cases had clinical symptoms, such as convulsions or dyskinesia. Although none had a cerebrospinal fluid/glucose ratio <0.4, the genetic report revealed that all had the solute carrier family 2 member 1 gene variant, and their clinical symptoms basically improved following the use of the KD. GLUT1-DS is a genetic metabolic disease that causes a series of neurological symptoms due to glucose metabolism disorders in the brain. Low glucose levels in cerebrospinal fluid and genetic testing are key diagnostic criteria, and the KD is a highly effective treatment option. By summarizing and analyzing patients with GLUT1-DS, summarizing clinical characteristics and expanding their gene profile, the findings of the present study may be of clinical significance for the early recognition and diagnosis of the disease, so as to conduct early treatment and shorten the duration of brain energy deficiency. This is of utmost importance for improving the prognosis and quality of life of affected children.

Keywords: children; epilepsy; glucose transporter type 1 deficiency syndrome; ketogenic diet; solute carrier family 2 member 1.

Figure 1

Structural analysis of WT and the variant SLC2A1 with mutations. The residues of missense mutant sites together with the nearby functional site are illustrated in WT and variant SLC2A1 using PyMol Viewer. The computed hydrogen bonds are shown as yellow dashed lines. Residues of the mutant sites are highlighted in orange solid lines. WT, wild-type.

Figure 2

Structural analysis of wild-type and the variant SLC2A1 with missense mutations and frameshift mutation. Protein prediction software (SWISS-MODEL) was used to predict the three-dimensional structure of proteins. (A) Wild-type, (B) case no. 1, (C) case no. 3, (D) case no. 4. (B-D) Case nos. 1, 3 and 4 were mutant.