glucose transporter deficiency mri

Glucose transporter type 1 (GLUT-1) deficiency is a rare cause of preventable intellectual disability. Intellectual disability is due to refractory seizures in infancy and reduced supply of glucose to the brain. The authors report a third born male child of consanguineous parentage who presented with infantile spasms. Initially, he had refractory convulsions of focal, generalised, and myoclonic jerks, not responding to multiple anticonvulsants. He also had choreoathetoid movements. On examination he had microcephaly...

Glucose transporter type 1 deficiency syndrome is characterized by infantile onset seizures, development delay, movement disorders, and acquired microcephaly. The phenotype includes allelic variants such as intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia of childhood with or without epilepsy. Dystonias involve allelic variants of glucose transporter type 1 deficiency syndrome. Three Chinese patients presented with paroxysmal behavioral disturbance, weakness, ataxia (especially after fasting), and exercise intolerance...

SLC2A8, also known as GLUT8, is a facilitative glucose transporter expressed in the testis, brain, liver, heart, uterus, ovary, and fat. In this study we examined the effect of Slc2a8 deficiency on mouse gamete, preimplantation embryo, and implantation phenotype, as well as postnatal growth and physiology. For this model, the transcriptional start site and exons 1-4 were targeted and a lack of protein expression was confirmed by Western immunoblot. Oocytes obtained from Slc2a8(-/-) mice demonstrated abnormal metabolism and ATP production...

CONTEXT: GLUT1 (glucose transporter 1) deficiency syndrome is a well-known presentation in pediatric practice. Very rare mutations not only disable carbohydrate transport but also cause the red cell membrane to be constitutively permeant to monovalent cations, namely sodium and potassium. OBJECTIVE: The aim of this study was to describe the pediatric presentation of a patient with GLUT1 deficiency with such a cation-leaky state. SUBJECT AND METHODS: The infant presented with erratic hyperkalemia, neonatal hyperbilirubinemia, anemia, hepatic dysfunction, and microcephaly...

Methylmalonic acidemia (MMA) is an inherited organic acidemia usually present with recurrent episodes of acute illness. A typical episode is ushered in with ketonuria and vomiting, followed by acidosis, dehydration, and lethargy, leading, in the absence of aggressive treatment, to coma and death. We report an infant with MMA presented with diabetes symptoms. A 13-month-old girl complained of polydipsia, diuresis, and loss of weight. She had clinical signs of diabetic ketoacidosis such as dehydration, deep sighing respiration, smell of ketones, lethargy, and vomiting...

Glut-1 facilitates the diffusion of glucose across the blood-brain barrier and is responsible for glucose entry into the brain. 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. Approximately 93% of patients with Glut-1 DS have identifiable mutations by sequence analysis in SLC2A1 which localizes to chromosome 1p34...

OBJECTIVE: To expand the spectrum of glucose transporter type 1 deficiency syndromes with a novel clinical and radiological phenotype not associated with microcephaly. DESIGN: Case report. SETTING: Two academic medical centers. Patient A 7-year-old patient followed up for 4 years. RESULTS: The patient exhibited a predominant syndrome of chorea and mental retardation associated with a combination of paroxysmal ataxia, dysarthria, dystonia and aggravated intellectual disability induced by fasting or exertion...

Paroxysmal exercise-induced dyskinesias (PED) are involuntary intermittent movements triggered by prolonged physical exertion. Autosomal dominant inheritance may occur. Recently, mutations in the glucose transporter 1 (GLUT1) gene (chr. 1p35-p31.3) have been identified as a cause in some patients with autosomal dominant PED. Mutations in this gene have previously been associated with the GLUT1 deficiency syndrome. We performed mutational analysis in 10 patients with apparently sporadic PED. We identified two novel GLUT1 mutations, at least one likely to be de-novo, in two of our patients...

Glucose transporter type 1 (Glut-1) facilitates glucose flux across the blood-brain-barrier. In humans, Glut-1 deficiency causes acquired microcephaly, seizures and ataxia, which are recapitulated in our Glut-1 haploinsufficient mouse model. Postnatal brain weight deceleration and development of reactive astrogliosis were significant by P21 in Glut-1(+/-) mice. The brain weight differences remained constant after P21 whereas the reactive astrocytosis continued to increase and peaked at P90. Brain immunoblots showed increased phospho-mTOR and decreased phospho-GSK3-beta by P14...

Paroxysmal exercise-induced dyskinesia (PED) can occur in isolation or in association with epilepsy, but the genetic causes and pathophysiological mechanisms are still poorly understood. We performed a clinical evaluation and genetic analysis in a five-generation family with co-occurrence of PED and epilepsy (n = 39), suggesting that this combination represents a clinical entity. Based on a whole genome linkage analysis we screened SLC2A1, encoding the glucose transporter of the blood-brain-barrier, GLUT1 and identified heterozygous missense and frameshift mutations segregating in this and three other nuclear families with a similar phenotype...

The behavioral effects of psychomotor stimulants such as amphetamine (AMPH) arise from their ability to elicit increases in extracellular dopamine (DA). These AMPH-induced increases are achieved by DA transporter (DAT)-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ). In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K) and protein kinase B (PKB, or Akt), which we have previously shown are able to fine-tune DAT cell-surface expression...

Monitoring effects of a ketogenic diet in GLUT1 deficiency syndrome without seizures is difficult. Neuroimaging is considered uninformative. We report the case of a boy with neurodevelopmental delay, severe ataxia, an E54X-mutation in the SLC2A1 gene (previously GLUT1), and neuroimaging abnormalities indicative of delayed myelination. Six months on a ketogenic diet resulted in an improved high subcortical white matter signal on T2-weighted images and a reduced N-acetylaspartate/creatine ratio. We conclude that delayed subcortical myelination may occur in GLUT1 deficiency syndrome as a nonspecific finding reflecting developmental delay...

The glucose transporter type 1 deficiency syndrome (GLUT-1 SD) (OMIM 606777) is an inborn error of metabolism of brain glucose transport. The characteristic clinical manifestations are seizures, hypotonia, developmental delay, microcephaly and hypoglycorrhachia. We report a girl with normal weight and height at birth. At 6 weeks of age she started with convulsions reaching up to 20 myoclonic seizures a day. She was treated with valproate, phenobarbital and carbamazepine without response. Blood analysis including aminoacids and acylcarnitines were all normal...

A de novo 4.1-megabase microdeletion of chromosome 1p34.2p34.3 has been identified by array-based comparative genomic hybridization in a young male with severely delayed development, microcephaly, pronounced hypotonia, and facial dysmorphism. The deleted region encompasses 48 genes, among them the glucose transporter 1 (SLC2A1 or GLUT1) gene. 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)...

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Myoglobin is an important intracellular O2 binding hemoprotein in heart and skeletal muscle. Surprisingly, disruption of myoglobin in mice (myo-/-) resulted in no obvious phenotype and normal cardiac function was suggested to be mediated by structural alterations that tend to steepen the oxygen pressure gradient from capillary to mitochondria. Here we report that lack of myoglobin causes a biochemical shift in cardiac substrate utilization from fatty acid to glucose oxidation. Proteome and gene expression analysis uncovered key enzymes of mitochondrial beta-oxidation as well as the nuclear receptor PPAR to be downregulated in myoglobin-deficient hearts...

PURPOSE OF REVIEW: Glucose transporter type 1 deficiency syndrome (OMIM 606777) is a treatable epileptic encephalopathy resulting from impaired glucose transport into the brain. In recent years, the increasing number of patients has generated substantial insights into the manifestations and mechanisms of this disease. Current understanding of this novel disorder is reviewed, and recent advances in diagnosis and treatment are highlighted. RECENT FINDINGS: The syndrome is now understood to be a complex neurological disorder...

Cerebral 18F-fluorodeoxyglucose positron emission tomography in 14 patients with microcephaly, developmental delay, seizures, and mutations of the glucose transporter Glut1 (Glut1 deficiency syndrome) showed distinct abnormalities. Within a global context of diminished cortical uptake, more severe hypometabolism was found in the mesial temporal regions and thalami, accentuating a relative signal increase in the basal ganglia. In contrast, the structure of the brain appeared preserved in patients additionally investigated by magnetic resonance imaging...