Glucose transporter type I deficiency syndrome: Epilepsy phenotypes and outcomes

Abstract

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.

Focal epilepsy in Glucose transporter type 1 (Glut1) defects: case reports and a review of literature

“…For the other cases, a detailed description is not included. In a cohort of 78 patients, 37 % suffered from focal dyscognitive seizures and 3 % with simple focal seizures [14]. The semiology of seizures is not provided.…”

A 23 years follow-up study identifies GLUT1 deficiency syndrome initially diagnosed as complicated hereditary spastic paraplegia

“…Intellectual disability was mild to moderate in severity and was not associated with microcephaly, which is a typical sign of GLUT1DS. Unlike the spectrum of focal and multifocal seizure types reported in the literature for GLUT1DS, the patients described here presented, especially in childhood, with a quite monomorphic clinical pattern compatible with a diagnosis of generalized epilepsy (Pong et al, 2012). Differences in epileptiform features appear even among patients with GLUT1DS harboring the SLC2A1 p.Arg126Cys mutation, in which typical absence seizures or myoclonic absences are the most prevalent seizure type reported (Gokben et al, 2011;Suls et al, 2009;Zorzi et al, 2008).…”

Glucose Transporter Type I Deficiency and Other Glucose Flux Disorders

“…Several seizure types have been described in these patients, including generalized tonic or clonic seizures, myoclonic seizures, atypical absence, atonic, infantile spasms and unclassified seizures. 19,20 The frequency of clinical seizures varies considerably from one patient to another. Some have daily seizures, whereas others have only occasional seizures separated by days, weeks, or months.…”

“…A ketogenic diet has led to about two-thirds of patients becoming seizure-free, most of which achieved seizure remission in less than a week. A minority of patients 20 As a rule, the clinical seizures respond poorly to antiepileptic drugs and disappear rapidly after beginning a ketogenic diet. Unfortunately, neurological deficits in motor control and cognition tend to persist under the diet, with a significant fraction (about one-third) of patients experiencing recurrent or incompletely treated abnormalities and reduced diet tolerability.…”