Bench Meets Bedside: A 10-Year-Old Girl and Amino Acid Residue Glycine 75 of the Facilitative Glucose Transporter GLUT1

Abstract

In 2000, amino acid residue G75 of the facilitative glucose transporter GLUT1 was identified by mutagenesis as being essential for transport function [Olsowski, A., et al. (2000) Biochemistry 39, 2469-74]. In 2002, we identified a heterozygous missense mutation substituting glycine at residue 75 for tryptophan in a 10-year-old girl with intractable seizures and low glucose concentrations in the cerebrospinal fluid indicative of GLUT1 deficiency. Glucose uptake into erythrocytes of the patient was 36% of controls, and GLUT1-specific immunoreactivity was normal, indicating a functional GLUT1 defect. In silico three-dimensional modeling of the G75W mutant provided a smaller gyration radius for transmembrane segment 2 as the potential pathogenic mechanism in this patient. This case illustrates a GLUT1 mutation characterized in vitro and later confirmed by disease itself and highlights the potential of basic science and clinical medicine to collaborate for the benefit of patients.