Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare genetic disorder due to mutations or deletions in SLC2A1, resulting in impaired glucose uptake through the blood brain barrier.
Mutations in SLC2A1, encoding the glucose transporter type 1 (Glut1), cause a wide range of neurological disorders: (1) classical Glut1 deficiency syndrome (Glut1-DS) with an early onset epileptic encephalopathy including a severe epilepsy, psychomotor delay, ataxia and microcephaly, (2) paroxysmal exercise-induced dyskinesia (PED) and (3) various forms of idiopathic/genetic generalized epilepsies such as different forms of absence epilepsies.
Glucose transporter type 1 deficiency syndrome (Glut-1DS) is caused by autosomal dominant haplodeficiency or autosomal recessive with homozygous mutation of the glucose transporter 1 (SLC2A1) gene and is characterized by severe seizures, developmental delay, ataxia and acquired microcephaly.
The corresponding mutations in GLUT1 (R153C and R333W) are known to cause GLUT1 deficiency syndrome because arginine residues in this motif are reportedly important as the determinants of the membrane topology of human GLUT1.
Impaired glucose transport across the blood-brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized in its most severe form by infantile seizures, developmental delay, acquired microcephaly, spasticity, ataxia, and hypoglycorrhachia.
A missense mutation in the SLC2A1 gene encoding the facilitative glucose transporter-1 (GLUT1) was recently described in a child fulfilling the existing criteria for the diagnosis of AHC, with the exception of age at onset, thus suggesting a clinical overlap between AHC and GLUT1 deficiency syndrome due to SLC2A1 mutations.
Emphasis is placed on transgenic GLUT1 overexpression and null mutant model systems, the latter serving as surrogates for the human GLUT1 deficiency syndrome.
GLUT1 deficiency syndrome (GLUT1DS) is understood as a monogenetic disease caused by heterozygous SLC2A1 gene mutations with autosomaldominant and sporadic transmission.
The deletion of the GLUT1 gene was in line with the abnormal ratio of cerebrospinal fluid (CSF) glucose to blood glucose, indicative of GLUT1 deficiency syndrome (MIM #606777).
In this study, the protein products of the Glut1DS-associated GLUT1 missense mutations, S66F, R126C, and T295M, were characterized using the Glut1-green fluorescent protein (GFP) fusion expressed in CHO cells.
The deletion of the GLUT1 gene was in line with the abnormal ratio of cerebrospinal fluid (CSF) glucose to blood glucose, indicative of GLUT1 deficiency syndrome (MIM #606777).