Abstracts

Rationale: Glucose transporter 1 (GLUT-1) deficiency is known to be responsible for infantile-onset and refractory epilepsy, developmental delay, acquired microcephaly and complex motor abnormalities. Accurate diagnosis of this treatable neurometabolic disorder is essential to initiate a ketogenic diet which can greatly improve this condition. We present two novel cases of genetically proven GLUT-1 haploinsufficiency which broaden the clinical spectrum of the disease. Methods: Those patients were followed both by the pediatric and neurology units of Strasbourg University Hospital. This longitudinal following included : clinical visits, video recordings, repeated wake and sleep video EEG, cognitive, radiological, biological and genetic explorationsResults: Patient 1 is a 18 years old female adult presenting with focal temporal epilepsy diagnosed at 1 year, moderate developmental delay and progressive microcephaly. In her early teens, she experienced recurrent episodes of faintness associated with palor and sweating, mainly triggered by fasting or exercise. She also presented paroxysmal ataxia and dystonic movements markedly worsened by exercise, fasting or coffee intake. Her glucose level in CSF was 0.36 g/L (as compared to 1.1 g/L in blood) and the mutation analysis of the GLUT-1 gene revealed a new mutation, absent in her parents. Her motor and cognitive abilities have been strikingly improved by the ketogenic diet. Patient 2 is a 10 years old male child presenting with prolonged episodes of paroxysmal ataxia and weakness related to exercise at the age of 2 years, associated with mild developmental delay with hyperactivity and deficit attention. His EEG showed frequent generalized SW, activated by sleep. His head circumference is still normal at 10 years of age. Glucose level in CSF was only very mildly decreased (0.43 g/l as compared to 0.87 g/l in blood) but the sequencing of the GLUT-1 gene confirmed a new mutation, absent in his parents. His attention and cognitive deficiency, paroxysmal ataxia, and EEG abnormalities have been largely responsive to the ketogenic diet. Conclusions: These two cases underline that suggestive clinical symptoms of GLUT-1 deficiency may appear years after the first signs of the disease and that acquired microcephaly notably may not be a constant feature. Even the characteristic hypoglycorrhachia may sometimes be difficult to demonstrate with certainty. The most prominent symptom of the disease seems to be the intolerance to exercise and fasting, with paroxysmal neurological symptoms, in those two patients.