Glucose transporter type I deficiency syndrome: Epilepsy phenotypes and outcomes

• Published in: Epilepsia (Copenhagen) 2012-09, Vol.53 (9), p.1503-1510
• Main Authors: Pong, Amanda W., Geary, Brianna R., Engelstad, Kris M., Natarajan, Ashwini, Yang, Hong, De Vivo, Darryl C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Antiepileptic agents; Antiepileptic drugs; Biological and medical sciences; Child; Child, Preschool; Children; Children & youth; Clinical trials; Cohort Studies; Complex syndromes; Diet, Ketogenic - methods; EEG; Epilepsy; Epilepsy - diet therapy; Epilepsy - genetics; Epilepsy - metabolism; Female; Glucose transporter; Glucose Transporter Type 1 - deficiency; Glucose Transporter Type 1 - genetics; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant; Infants; Ketogenesis; Ketogenic diet; ketones; Male; Medical genetics; Medical sciences; Metabolic disorders; Microencephaly; Middle Aged; Nervous system (semeiology, syndromes); Neurology; Pediatric epilepsy; Phenotype; Retrospective Studies; Seizures; Syndrome; Treatment Outcome; Young Adult
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2012.03592.x

Summary Purpose:  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