Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: A successful use of zonisamide for controlling the seizures

Takahashi, Satoru; Ohinata, Junko; Suzuki, Nao; Amamiya, Satoshi; Kajihama, Aya; Sugai, Rika; Araki, Akiko; Fukui, Kenji; Tanaka, Hajime

doi:10.1016/j.eplepsyres.2008.03.010

Cited by 14 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…If direct sequencing yielded normal results, large rearrangements of SCL2A1 were examined using the Multiple Ligation Probe Amplification (MLPA) method. The details of these methods were described elsewhere [20,21].…”

Section: Methodsmentioning

confidence: 99%

“…Approximately 200 cases of GLUT-1DS have been reported to date, mainly in the US and Europe [17]. There have also been sporadic reports in Japan since 1991 [18][19][20][21]. Although epileptic seizures in GLUT-1DS patients are often refractory to antiepileptic drug treatments, ketogenic diet therapy (KD) is an effective and causal therapeutic method that can supply ketone bodies instead of glucose as a source of brain energy [22][23][24].…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Nationwide survey of glucose transporter-1 deficiency syndrome (GLUT-1DS) in Japan

Ito

Takahashi

Kagitani‐Shimono

et al. 2015

Brain and Development

Self Cite

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Nationwide survey of glucose transporter-1 deficiency syndrome (GLUT-1DS) in Japan

Ito

Takahashi

Kagitani‐Shimono

et al. 2015

Brain and Development

Self Cite

View full text Add to dashboard Cite

“…The Arg333Trp mutation, identified in patients 1 and 3, has already been described in several patients, confirming a hot spot. 8,15,16 Although details of the epilepsy in these cases are incomplete, the phenotypes appear to vary from classic encephalopathy with infantile seizures and microcephaly to epilepsy consistent with MAE. Mutagenesis studies on both the arginine residues (Arg 333 and Arg400) involved in the mutations in patients 1, 2, and 3 have been published and show reduced glucose transport due to interference with glucose-induced conformational changes in the GLUT1 protein.…”

Section: Commentmentioning

confidence: 99%

Glucose Transporter 1 Deficiency as a Treatable Cause of Myoclonic Astatic Epilepsy

et al. 2011

View full text Add to dashboard Cite

ObjectiveTo determine if a significant proportion of patients with myoclonic-astatic epilepsy (MAE) have glucose transporter 1 (GLUT1) deficiency.DesignGenetic analysis.SettingAmbulatory and hospitalized care.PatientsEighty-four unrelated probands with MAE were phenotyped and SLC2A1 was sequenced and analyzed by multiplex ligation-dependent probe amplification. Any identified mutations were then screened in controls.Main Outcome MeasureAny SLC2A1 mutations.ResultsFour of 84 probands with MAE had a mutation of SLC2A1 on sequencing. Multiplex ligation-dependent probe amplification analysis did not reveal any genomic rearrangements in 75 of the remaining cases; 5 could not be tested. Two patients with MAE with SLC2A1 mutations also developed paroxysmal exertional dyskinesia in childhood.ConclusionsFive percent of our patients with MAE had SLC2A1 mutations, suggesting that patients with MAE should be tested for GLUT1 deficiency. Diagnosis of GLUT1 deficiency is a strong indication for early use of the ketogenic diet, which may substantially improve outcome of this severe disorder.

show abstract

“…Significant controversy exists regarding the appropriate treatment of Glut 1 DS, especially when KD is not feasible or sufficient. Standard AEDs have been used in the majority of patients before their diagnosis, and some patients continue to take AEDs after diagnosis (Klepper et al, 2005;Takahashi et al, 2008). However, in vitro evidence of Glut 1 inhibition suggests that particular AEDs, namely phenobarbital (Klepper et al, 1999), valproic acid (Wong et al, 2005), and benzodiazepines, may be associated with exacerbation when used in clinical treatment (Klepper et al, 2003).…”

mentioning

confidence: 99%

Glucose transporter type I deficiency syndrome: Epilepsy phenotypes and outcomes

et al. 2012

View full text Add to dashboard Cite

SUMMARYPurpose: Glut 1 deficiency syndrome (DS) is defined by hypoglycorrhachia with normoglycemia, acquired microcephaly, episodic movements, and epilepsy refractory to standard antiepileptic drugs (AEDs). Gold standard treatment is the ketogenic diet (KD), which provides ketones to treat neuroglycopenia. Our purpose is (1) to describe epilepsy phenotypes in a large Glut 1 DS cohort, to facilitate diagnosis; and (2) to describe cases in which non-KD agents achieved seizure freedom (SF), highlighting potential adjunctive treatments. Methods: Retrospective review of 87 patients with Glut 1 DS (45% female, age range 3 months-35 years, average diagnosis 6.5 years) at Columbia University, from 1989 to 2010. Key Findings: Seventy-eight (90%) of 87 patients had epilepsy, with average onset at 8 months. Seizures were mixed in 68% (53/78): generalized tonic-clonic (53%), absence (49%), complex partial (37%), myoclonic (27%), drop (26%), tonic (12%), simple partial (3%), and spasms (3%). We describe the first two cases of spasms in Glut 1 DS. Electrophysiologic abnormalities were highly variable over time; only 13 (17%) of 75 had exclusively normal findings. KD was used in 82% (64/78); 67% (41/61) were seizure-free and 68% of seizure-free patients (28/41) resolved in <1 week and 76% (31/41) in <1 month. Seven patients achieved SF with broad agents only. Significance: Glut 1 DS is a genetic metabolic encephalopathy with variable focal and multifocal seizure types and electroencephalographic findings. Infants with seizures, spasms, or paroxysmal events should be tested for Glut 1 DS. Evidence is insufficient to recommend specific AEDs as alternatives to KD. Early diagnosis and initiation of KD and prevention of unnecessary AED trials in Glut 1 DS are important goals for the treatment of children with epilepsy.

show abstract

Molecular analysis and anticonvulsant therapy in two patients with glucose transporter 1 deficiency syndrome: A successful use of zonisamide for controlling the seizures

Abstract: Glucose transporter 1 (GLUT1) deficiency syndrome is caused by a deficit in glucose transport to the brain during the pre-and postnatal periods. Here we report two cases of GLUT1 deficiency syndrome diagnosed on the basis of clinical features, reduced

Cited by 14 publications

References 23 publications

Nationwide survey of glucose transporter-1 deficiency syndrome (GLUT-1DS) in Japan

Nationwide survey of glucose transporter-1 deficiency syndrome (GLUT-1DS) in Japan

Glucose Transporter 1 Deficiency as a Treatable Cause of Myoclonic Astatic Epilepsy

Glucose transporter type I deficiency syndrome: Epilepsy phenotypes and outcomes

Contact Info

Product

Resources

About