Prevalence of Genetic Disorders and GLUT1 Deficiency in a Ketogenic Diet Clinic

Hewson, Stacy; Brunga, Ledia; Ojeda, Matilde Fernandez; Imhof, E; Patel, Jaina; Zak, Maria; Donner, Elizabeth; Kobayashi, Jeff; Salomons, Gajja S.; Mercimek‐Andrews, Saadet

doi:10.1017/cjn.2017.246

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…Ramm-Pettersen ( 29 ) demonstrated following the long-term observation of patients with GLUT1-DS, that those who were diagnosed and started the KD within a few months after birth had better psychomotor development, while those who commenced the KD later significantly lagged behind their peers. This conclusion has also been verified by other studies ( 11 , 22 ).…”

Section: Discussionsupporting

confidence: 90%

“…Generalized epileptiform spike-wave patterns are the most common. Hewson et al ( 22 ) reviewed the seizure patterns of 99 patients with GLUT-DS, of whom 89% had extensive spikes or spike-wave electrical activity on EEG. Of all seizure types, generalized tonic-clonic seizures are the most common, and other heterogeneous seizure types, including absence, myoclonic and tonic-clonic seizures have also been reported ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

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Clinical and genetic analysis of children with glucose transporter type 1 deficiency syndrome

Qian,

Ying,

et al. 2024

Med Int

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Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare metabolic encephalopathy with a wide variety of clinical phenotypes. In the present study, 15 patients diagnosed with GLUT1-DS were selected, all of whom had obvious clinical manifestations and complete genetic testing. Their clinical data and genetic reports were collated. All patients were provided with a ketogenic diet (KD) and an improvement in their symptoms was observed during a follow-up period of up to 1 year. The results revealed that the 15 cases had clinical symptoms, such as convulsions or dyskinesia. Although none had a cerebrospinal fluid/glucose ratio <0.4, the genetic report revealed that all had the solute carrier family 2 member 1 gene variant, and their clinical symptoms basically improved following the use of the KD. GLUT1-DS is a genetic metabolic disease that causes a series of neurological symptoms due to glucose metabolism disorders in the brain. Low glucose levels in cerebrospinal fluid and genetic testing are key diagnostic criteria, and the KD is a highly effective treatment option. By summarizing and analyzing patients with GLUT1-DS, summarizing clinical characteristics and expanding their gene profile, the findings of the present study may be of clinical significance for the early recognition and diagnosis of the disease, so as to conduct early treatment and shorten the duration of brain energy deficiency. This is of utmost importance for improving the prognosis and quality of life of affected children.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Clinical and genetic analysis of children with glucose transporter type 1 deficiency syndrome

Qian,

Ying,

et al. 2024

Med Int

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“…This (Vanoye et al, 2014) *Non genetic origin mutations reported: Mutations described through clinical diagnosis, but the mutation type (Mendelian or de novo) were not reported, mainly due to the lack of parents to perform genotyping and difficulty in contacting the family. DII (S1) Missense NR (Butler et al, 2017b;Hewson et al, 2018;Lindy et al, 2018;Costain et al, 2019;Johannesen et al, 2019) T767I DII (S1) Missense Decreased current density Increased current amplitude provokes by voltage ramp protocol (Estacion et al, 2014;Gardella et al, 2018;Lindy et al, (Fung et al, 2015;Zhang et al, 2015;Lindy et al, 2018;Kim et al, 2019;Tsang et al, 2019;Pan and Cummins, 2020;Schreiber et al, DIII (S6)-DIV (S1) Missense NR (Pons et al, 2018;Denis et al, 2019) G1475R DIII (S6)-DIV (S1) Missense Enhanced persistent current (Hussain et al, 2016;Ortiz Madinaveitia et al, 2017;Parrini et al, 2017;Wang et al, 2017a;Gardella et al, 2018;Lindy et al, 2018;Xiao et al, 2018;Kim et al, 2019;Trivisano et al, 2019;Zaman et al, 2019;Ranza et al, 2020;Schreiber et al, 2020) G1476S DIII (S6)-DIV (S1) Missense NR (Lindy et al, 2018) I1479V DIII (S6)-DIV (S1) Missense NR (Larsen et al, 2015;Lindy et al, 2018;Schreiber et al, 2020) E1483K DIII (S6)-DIV (S1) Missense NR (Johannesen et al, 20...…”

Section: Nav16mentioning

confidence: 99%

Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review

et al. 2020

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Epilepsy is a disease characterized by abnormal brain activity and a predisposition to generate epileptic seizures, leading to neurobiological, cognitive, psychological, social, and economic impacts for the patient. There are several known causes for epilepsy; one of them is the malfunction of ion channels, resulting from mutations. Voltage-gated sodium channels (NaV) play an essential role in the generation and propagation of action potential, and malfunction caused by mutations can induce irregular neuronal activity. That said, several genetic variations in NaV channels have been described and associated with epilepsy. These mutations can affect channel kinetics, modifying channel activation, inactivation, recovery from inactivation, and/or the current window. Among the NaV subtypes related to epilepsy, NaV1.1 is doubtless the most relevant, with more than 1500 mutations described. Truncation and missense mutations are the most observed alterations. In addition, several studies have already related mutated NaV channels with the electrophysiological functioning of the channel, aiming to correlate with the epilepsy phenotype. The present review provides an overview of studies on epilepsy-associated mutated human NaV1.1, NaV1.2, NaV1.3, NaV1.6, and NaV1.7.

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“…The prevalence of GLUT1DS ranged from 0.9 to 2.4% in our previous studies. 8,9,12 Prior to 2015, there were two patients diagnosed with GLUT1DS, known to us at our institution. Since the availability of targeted next-generation sequencing panels and whole-exome sequencing in clinical settings, we have confirmed the diagnosis of GLUT1DS in more than 10 patients at our institution.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Genotypic Spectrum of Glucose Transporter-1 Deficiency Syndrome

Bourque

Cordeiro

Nimmo

et al. 2021

Can. J. Neurol. Sci.

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Background: Glucose Transporter-1 (GLUT1) Deficiency Syndrome (GLUT1DS) is caused by defective transport of glucose across the blood–brain barrier into brain cells resulting in hypoglycorrhachia due to the heterozygous pathogenic variants in SLC2A1. We report on the phenotypic spectrum of patients with pediatric GLUT1DS as well as their diagnostic methods from a single center in Canada. Methods: We reviewed patient charts for clinical features, biochemical and molecular genetic investigations, neuroimaging, treatment modalities, and outcomes of patients with GLUT1DS at our institution. Results: There were 13 patients. The most common initial symptom was seizures, with the most common seizure type being absence seizures (85%). Seventy-seven percent of the patients had movement disorders, and dystonia and ataxia were the most common movement disorders. Fifty-four percent of the patients did not have a history of developmental delay during their initial presentation, whereas all patients had developmental delay, intellectual disability, or cognitive dysfunction during their follow-up. All patients had a pathogenic or likely pathogenic variant in SLC2A1 and missense variants were the most common variant type. Conclusion: We present 13 patients with GLUT1DS in the pediatric patient population. Atypical clinical features such as hemiplegia and hemiplegic migraine were present in an infant; there was a high prevalence of absence seizures and movement disorders in our patient population. We report an increased number of patients with GLUT1DS since the introduction of next-generation sequencing in the clinical settings. We believe that GLUT1DS should be included in the differential diagnosis of seizures, movement disorders, and hemiplegic migraine.

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Prevalence of Genetic Disorders and GLUT1 Deficiency in a Ketogenic Diet Clinic

Cited by 5 publications

References 9 publications

Clinical and genetic analysis of children with glucose transporter type 1 deficiency syndrome

Clinical and genetic analysis of children with glucose transporter type 1 deficiency syndrome

Epilepsy-Related Voltage-Gated Sodium Channelopathies: A Review

Phenotypic and Genotypic Spectrum of Glucose Transporter-1 Deficiency Syndrome

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