To examine correlations between the genetic, biochemical, and clinical characteristics in glucose transporter 1 deficiency syndrome (GLUT1DS).

Few clinical studies have been conducted on genotype-phenotype correlations among GLUT1DS.

We retrospectively reviewed clinical data from our hospital’s medical records. Between August 2009 and September 2018, we performed a genetic analysis on the SLC2A1 gene in patients who were admitted to our hospital. We diagnosed 39 patients by genetic analysis or the 3OMG uptake test. We collected data on the developmental quotient (DQ) in 18 patients based on the Kyoto scale of psychological development; the Scale for the Assessment and Rating of Ataxia (SARA) was used to assess 23 patients. A cerebrospinal fluid (CSF) analysis assessing CSF glucose (CSFG) and the CSF:blood glucose ratio (CBGR) had previously been performed in all patients. We compared the results of the DQ, SARA, CSFG, CBGR, and genotype among the patients. Genotype was divided into two subtypes: group I included nonsense, frameshift, and splice site mutations and large deletions involving several exons; and group II included missense mutations. The correlations between the DQ, SARA, and biochemical characteristics were tested using Pearson’s correlation coefficient test, and the difference between clinical characteristics and genotype subtypes were tested using the Mann-Whitney U test. The genetic analysis and this study were conducted with the permission of our hospital’s ethical committee.

The statistical analysis reported significant phenotype-biochemical correlations: r = 0.70 (p=0.001) for DQ vs CSFG; r = 0.68 (p=0.002) for DQ vs CBGR; r = -0.76 (p<0.001) for SARA vs CSFG; and r = -0.78 (p<0.001) for SARA vs CBGR. Patients with group I mutation had more severe phenotype. The statistical analysis showed significant difference: p=0.001 for the DQ and p<0.001 for the SARA.

Phenotype in GLUT1DS is determined by biochemical and genetic characters.