seizure glut1

Glucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up...

Glucose transporter type 1 (GLUT1) is the most important energy carrier of the brain across the blood-brain barrier, and a genetic defect of GLUT1 is known as GLUT1 deficiency syndrome (GLUT1DS). It is characterized by early infantile seizures, developmental delay, microcephaly, ataxia, and various paroxysmal neurological phenomena. In most cases, GLUT1DS is caused by heterozygous single-nucleotide variants (SNVs) in the SLC2A1 gene that provoke complete or severe impairment of the functionality and/or expression of GLUT1 in the brain...

We describe a cohort of 10 unrelated Greek patients (4 females, 6 males; median age 6.5 years, range 2-18 years) with heterogeneous epilepsy syndromes with a genetic basis. In these patients, causative genetic variants, including two novel ones, were identified in 9 known epilepsy-related genes through whole exome sequencing. A patient with glycine encephalopathy was a compound heterozygote for the p.Arg222Cys and the p.Ser77Leu AMT variant. A patient affected with Lafora disease carried the homozygous p...

Neonatal seizures (NS) occur in the first 28 days of life; they represent an important emergency that requires a rapid diagnostic work-up to start a prompt therapy. The most common causes of NS include: intraventricular haemorrhage, hypoxic-ischemic encephalopathy, hypoglycemia, electrolyte imbalance, neonatal stroke or central nervous system infection. Nevertheless, an Inborn Error of Metabolism (IEM) should be suspected in case of NS especially if these are resistant to common antiseizure drugs (ASDs) and with metabolic decompensation...

BACKGROUND: GLUT1 Deficiency Syndrome 1 (GLUT1DS1) is a neurological disorder caused by either heterozygous or homozygous mutations in the Solute Carrier Family 2, Member 1 (SLC2A1) gene. SLC2A1 encodes Glucose transporter type 1 (GLUT1) protein, which is the primary glucose transporter at the blood-brain barrier. A ketogenic diet (KD) provides an alternative fuel for brain metabolism to treat impaired glucose transport. By reanalyzing exome data, we identified a de novo heterozygous SLC2A1 variant in a girl with epilepsy...

Background: Glucose-transporter-1 deficiency syndrome (GLUT1-DS), due to SLC2A1 gene mutation, is characterized by early-onset seizures, which are often drug-resistant, developmental delay, and hypotonia. Hemiplegic migraine (HM) is a rare form of migraine, defined by headache associated with transient hemiplegia, and can be caused by mutations in either CACNA1A, ATP1A2 , or SCN1A . Paroxysmal movements, other transient neurological disorders, or hemiplegic events can occur in GLUT1-DS patients with a mild phenotype...

BACKGROUND: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. METHODS: An observational descriptive study was conducted to describe 18 children (January 2009-August 2020)...

The ketogenic diet (KD) is an established, nonpharmacological treatment for drug-resistant epilepsy (DRE). Actually, KD and its variants have been shown to be elective and resolute for patients with glucose transporter type 1 (GLUT1) deficiency. The aim of this review was to study the use of KD and its variants in infancy, including the neonatal age, and demonstrate the safety and efficacy of this treatment in patients with the age of 0-23 months affected by DRE already subjected to pharmacological approach attempts...

Objective: To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT). Methods: Clinical data of 19 children with GLUT1 DS admitted to Children's Hospital of Fudan University, Tianjin Children's Hospital, Shenzhen Children's Hospital, Children's Hospital of Nanjing Medical University and Jiangxi Provincial Children's Hospital between 2015 and 2019 were collected retrospectively. The first onset symptom, main clinical manifestations, cerebrospinal fluid features and genetic testing results of patients were summarized, the efficacy and safety of ketogenic diet treatment were analyzed...

Cerebral metabolism is primarily dependent on glucose for which a facilitated diffusion by glucose transporter protein 1 (GLUT1) across the blood-brain barrier is crucial. This GLUT1 is encoded by the SLC2A1 gene. Mutations in SLC2A1 will lead to a variety of symptoms known as GLUT1 deficiency syndrome. In this article, we report a novel heterozygous intronic variant c.1278+12delC in the SLC2A1 gene in a Saudi patient with myoclonic epilepsy. We also report a new clinical phenotype where the patient has pure myoclonic epilepsy with no focal, absence, or atonic seizures and normal developmental and cognitive functions that started in childhood rather than infancy...

Glut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism. The increasing complexity of Glut1DS, since its original description in 1991, now demands an international consensus statement regarding diagnosis and treatment...

Lactate is used as an energy source by producer cells or shuttled to neighboring cells and tissues. Both glucose and lactate fulfill the bioenergetic demand of neurons, the latter imported from astrocytes. The contribution of astrocytic lactate to neuronal bioenergetics and the mechanisms of astrocytic lactate production are incompletely understood. Through in vivo1 H magnetic resonance spectroscopy, 13 C glucose mass spectroscopy, and electroencephalographic and molecular studies, here we show that the energy sensor AMP activated protein kinase (AMPK) regulates neuronal survival in a non-cell-autonomous manner...

BACKGROUND: Growth failure and growth hormone deficiency (GHD) have been reported as one accessory feature of GLUT1 deficiency syndrome (GLUT1DS), considered so far as a long-term adverse effects of ketogenic diet which is used to treat this condition. CASE PRESENTATION: We report the case of a 10-year-old Caucasian boy referred for short stature (height - 2.56 SDS) and delayed growth (growth velocity - 4.33 SDS) who was diagnosed with GHD and started treatment with recombinant human growth hormone (rhGH)...

INTRODUCTION: Glucose Transporter Type 1 Deficiency Syndrome (GLUT1-DS) is caused by the SLC2A1 gene muta tion, which encodes the glucose transporter proteins to the brain Neurological manifestations occur in three main domains: seizures, abnormal movements, and cognitive disorders. The diagnosis is presumed upon the finding of low CSF glucose and confirmed by the gene molecular analysis. Ac curate diagnosis is important because it has a specific treatment, which is ketogenic diet. OBJECTIVE: To analyze two SD-GLUT1 pediatric patients with unusual phenotype...

Metabolic epilepsies arise in the context of rare inborn errors of metabolism (IEM), notably glucose transporter type 1 deficiency syndrome, succinic semialdehyde dehydrogenase deficiency, pyruvate dehydrogenase complex deficiency, nonketotic hyperglycinemia, and mitochondrial cytopathies. A common feature of these disorders is impaired bioenergetics, which through incompletely defined mechanisms result in a wide spectrum of neurological symptoms, such as epileptic seizures, developmental delay, and movement disorders...

Epilepsy is a serious neurological disorder affecting around 70 million people globally and is characterized by spontaneous recurrent seizures. Recent evidence indicates that dysfunction in metabolic processes can lead to the alteration of neuronal and network excitability, thereby contributing to epileptogenesis. Developing a suitable animal model that can recapitulate all the clinical phenotypes of human metabolic epilepsy (ME) is crucial yet challenging. The specific environment of many symptoms as well as the primary state of the applicable neurobiology, genetics, and lack of valid biomarkers/diagnostic tests are the key factors that hinder the process of developing a suitable animal model...

Rationale: Endothelial cells (ECs) are highly glycolytic and generate the majority of their energy via the breakdown of glucose to lactate. At the same time, a main role of ECs is to allow the transport of glucose to the surrounding tissues. The facilitative glucose transporter isoform 1 (GLUT1/Slc2a1) is highly expressed in ECs of the central nervous system (CNS), and is often implicated in blood-brain barrier (BBB) dysfunction, but whether and how GLUT1 controls EC metabolism and function is poorly understood...

Insulin-mediated signaling in the brain is critical for neuronal functioning. Insulin resistance is implicated in the development of some neurological diseases, although changes associated with absence epilepsy have not been established yet. Therefore, we examined the major components of PI3K/Akt-mediated insulin signaling in cortical, thalamic, and hippocampal tissues collected from Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non-Epileptic Control (NEC) rats. Insulin levels were also measured in plasma and cerebrospinal fluid (CSF)...

OBJECTIVE: Glucose transporter type 1 deficiency (G1D) syndrome is generally a genetic disorder because of a mutation of the SLC2A1 gene. The clinical picture of G1D is heterogeneous. The aim of this paper was to present the case of G1D, recognized in a three-generation family, caused by missense mutation p.Arg92Trp in SLC2A1 gene, and showing high clinical heterogeneity and evolution of symptoms over time. METHODS: Three-generation family members, showing symptoms suggesting G1D, have been characterized in terms of the clinical picture, electroencephalogram (EEG) recordings, brain neuroimaging, and the psychological assessment data...

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate...