Glucose transporter type I deficiency syndrome: epilepsy phenotypes and outcomes.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Neurological Institute, Columbia University, New York, New York, USA. amandapong@yahoo.com
Amanda W
AW
Pong
Brianna R
BR
Geary
Kris M
KM
Engelstad
Ashwini
A
Natarajan
Hong
H
Yang
Darryl C
DC
De Vivo
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D055423:Diet, Ketogenic / Q000379:methods; D004827:Epilepsy / Q000178:diet therapy / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D013577:Syndrome; D016896:Treatment Outcome; D055815:Young Adult
D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human