Glucose Transporter 1 deficiency and associated conditions in children

The article reviews literature devoted to the glucose transporter type I deficiency syndrome (synonyms: GLUT1 deficiency syndrome, de Vivo disease), that is a genetically determined disease caused by pathogenic variants of the SLC2A1 gene. The insufficiency of this protein leads to the disruption of glucose delivery to the brain through the blood-brain barrier. Clinically, the syndrome is manifested by epileptic seizures (mainly as absences or myoclonic seizures), various motor disorders and psychomotor retardation starting from the early age.Early diagnosis (including molecular genetic analysis of the SLC2A1 gene) enables us to start treatment and prevent progression of the symptoms, and to provide the family with genetic consultation on the prognosis and risks for the next generations. Ketogenic diet is an effective treatment option for this pathological condition, it can lead to a regression of the clinical manifestations, especially on the early stage.

Download Full-text

SLC2A1 gene analysis of Japanese patients with glucose transporter 1 deficiency syndrome

Journal of Human Genetics ◽

10.1038/jhg.2011.115 ◽

2011 ◽

Vol 56 (12) ◽

pp. 846-851 ◽

Cited By ~ 12

Author(s):

Natsuko Hashimoto ◽

Kuriko Kagitani-Shimono ◽

Norio Sakai ◽

Takanobu Otomo ◽

Koji Tominaga ◽

...

Keyword(s):

Glucose Transporter ◽

Japanese Patients ◽

Deficiency Syndrome ◽

Gene Analysis ◽

Glucose Transporter 1 ◽

Slc2a1 Gene

Download Full-text

Another Case of Glucose Transporter 1 Deficiency Syndrome with Periventricular Calcification, Cataracts, Hemolysis, and Pseudohyperkalemia

Neuropediatrics ◽

10.1055/s-0037-1603520 ◽

2017 ◽

Vol 48 (05) ◽

pp. 390-393 ◽

Cited By ~ 2

Author(s):

Katsuhiro Kobayashi ◽

Harumi Yoshinaga ◽

Hiroaki Ono ◽

Michiko Shinpo ◽

Kuriko Kagitani-Shimono ◽

...

Keyword(s):

Glucose Transporter ◽

Clinical Symptoms ◽

Laboratory Data ◽

Diet Therapy ◽

Deficiency Syndrome ◽

Clinical Findings ◽

Red Cell Membrane ◽

Glucose Transporter 1 ◽

Eeg Abnormalities ◽

Slc2a1 Gene

AbstractGlucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) is a disorder resulting from shortage of energy in the brain caused by reduced GLUT1 activity. Its common clinical symptoms include seizures, microcephaly, intellectual disability, abnormal ocular movements, ataxia, and dystonia. We report a case of GLUT1DS with unusual symptoms, including periventricular calcification. The patient is a Japanese girl, whose seizures had always evolved into status epilepticus since she was 4 months old. She also had cataracts and horizontal nystagmus. Neuroimaging studies showed periventricular calcification and brain atrophy. Laboratory data revealed pseudohyperkalemia, reticulocyte increase, and hypoglycorrhachia. A mutation of c1306_1308delATC (p.Ile436del) was identified in the SLC2A1 gene, and she was thus diagnosed with GLUT1DS. A case with the identical SLC2A1 gene mutation and similar clinical findings was previously reported by Bawazir et al (2012). The leak of monovalent cations through the red cell membrane causes hemolysis in such patients, and a similar phenomenon may occur at the blood–brain barrier and the lens epithelium. After commencing ketogenic diet therapy, the electroencephalogram (EEG) abnormalities improved markedly and the patient's development advanced. Clinicians should be aware of atypical GLUT1DS.

Download Full-text

Alternating Hemiplegia of Childhood in an Infant with Symptoms Resembling Glucose Transporter 1 Deficiency

Journal of Pediatric Neurology ◽

10.1055/s-0037-1598026 ◽

2017 ◽

Vol 15 (04) ◽

pp. 180-182

Author(s):

Mini Sreedharan ◽

Shiji Chalipat ◽

Kunju Mohammed ◽

Kalpana Devadathan

Keyword(s):

Developmental Delay ◽

Glucose Transporter ◽

Gene Mutations ◽

Deficiency Syndrome ◽

Global Developmental Delay ◽

Glucose Transporter 1 ◽

Alternating Hemiplegia Of Childhood ◽

Slc2a1 Gene ◽

Glut1 Deficiency ◽

Atp1a3 Gene

AbstractGlucose transporter type 1 (glut1) deficiency syndrome presents with developmental delay, microcephaly, and recurrent seizures during infancy, as well as cerebrospinal fluid (CSF) hypoglycorrhachia and mutations in the SLC2A1 gene. We describe a baby with microcephaly, global developmental delay, seizures from 3 months of age, and CSF glucose in the lower limit of normal range, with heterozygous p.Glu815Lys mutation of the ATP1A3 gene and no mutation in the SLC2A1 gene. Mutations in ATP1A3 gene are associated with alternating hemiplegia of childhood (AHC). Interestingly the baby developed episodes of recurrent bouts of alternating hemiplegia from 13 months of age. The case is reported to highlight ATP1A3 mutation as a probable etiology for glut1 deficiency like syndrome and AHC. A brief review of literature emphasizing the overlapping paroxysmal and nonparoxysmal symptoms of the two conditions is also included.

Download Full-text

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000159 ◽

2013 ◽

Vol 83 (3) ◽

pp. 188-197 ◽

Cited By ~ 21

Author(s):

Rebecca L. Sweet ◽

Jason A. Zastre

Keyword(s):

Gene Expression ◽

Thiamine Deficiency ◽

Glucose Transporter ◽

Neuroblastoma Cell ◽

Hypoxia Inducible Factor ◽

Clinical Manifestations ◽

Vitamin B1 ◽

Low Oxygen ◽

Glucose Transporter 1 ◽

Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

Download Full-text

A Case Report of Glucose Transporter 1 Deficiency Syndrome with a Novel Splice Site Mutation (SLC2A1: c.680-2delA)

Journal of the korean child neurology society ◽

10.26815/jkcns.2014.22.3.182 ◽

2014 ◽

Vol 22 (3) ◽

pp. 182-185

Author(s):

신종수 ◽

김성환 ◽

이문정

Keyword(s):

Case Report ◽

Splice Site ◽

Glucose Transporter ◽

Splice Site Mutation ◽

Deficiency Syndrome ◽

Site Mutation ◽

Glucose Transporter 1

Download Full-text

Epilepsy and glucose transporter 1 deficiency syndrome

Journal of Pediatric Epilepsy ◽

10.3233/pep-14091 ◽

2015 ◽

Vol 03 (04) ◽

pp. 191-198

Author(s):

Daryl Vivo ◽

Cigdem Akman

Keyword(s):

Glucose Transporter ◽

Deficiency Syndrome ◽

Glucose Transporter 1

Download Full-text

Glucose Transporter-1 (GLUT1) Deficiency Syndrome: Diagnosis and Treatment in Late Childhood

Neuropediatrics ◽

10.1055/s-0032-1315433 ◽

2012 ◽

Vol 43 (03) ◽

pp. 168-171 ◽

Cited By ~ 9

Author(s):

Gwendolyn Gramer ◽

Nicole Wolf ◽

Daniel Vater ◽

Thomas Bast ◽

René Santer ◽

...

Keyword(s):

Glucose Transporter ◽

Deficiency Syndrome ◽

Diagnosis And Treatment ◽

Late Childhood ◽

Glucose Transporter 1 ◽

Syndrome Diagnosis ◽

Glut1 Deficiency ◽

Glut1 Deficiency Syndrome

Download Full-text

Stomatin-deficient cryohydrocytosis results from mutations in SLC2A1: a novel form of GLUT1 deficiency syndrome

Blood ◽

10.1182/blood-2010-12-326645 ◽

2011 ◽

Vol 118 (19) ◽

pp. 5267-5277 ◽

Cited By ~ 42

Author(s):

Joanna F. Flatt ◽

Hélène Guizouarn ◽

Nicholas M. Burton ◽

Franck Borgese ◽

Richard J. Tomlinson ◽

...

Keyword(s):

Glucose Transporter ◽

Deficiency Syndrome ◽

Glucose Transporter 1 ◽

3 Dimensional ◽

Transporter Protein ◽

Expression Studies ◽

Glut1 Deficiency ◽

Glut1 Deficiency Syndrome ◽

Reticulocyte Maturation ◽

Exercise Induced

Abstract The hereditary stomatocytoses are a series of dominantly inherited hemolytic anemias in which the permeability of the erythrocyte membrane to monovalent cations is pathologically increased. The causative mutations for some forms of hereditary stomatocytosis have been found in the transporter protein genes, RHAG and SLC4A1. Glucose transporter 1 (glut1) deficiency syndromes (glut1DSs) result from mutations in SLC2A1, encoding glut1. Glut1 is the main glucose transporter in the mammalian blood-brain barrier, and glut1DSs are manifested by an array of neurologic symptoms. We have previously reported 2 cases of stomatin-deficient cryohydrocytosis (sdCHC), a rare form of stomatocytosis associated with a cold-induced cation leak, hemolytic anemia, and hepatosplenomegaly but also with cataracts, seizures, mental retardation, and movement disorder. We now show that sdCHC is associated with mutations in SLC2A1 that cause both loss of glucose transport and a cation leak, as shown by expression studies in Xenopus oocytes. On the basis of a 3-dimensional model of glut1, we propose potential mechanisms underlying the phenotypes of the 2 mutations found. We investigated the loss of stomatin during erythropoiesis and find this occurs during reticulocyte maturation and involves endocytosis. The molecular basis of the glut1DS, paroxysmal exercise-induced dyskinesia, and sdCHC phenotypes are compared and discussed.

Download Full-text