Abstracts

Rationale: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is the result of impaired glucose transport into the brain. The classical syndrome with infantile seizures, developmental delay, acquired microcephaly, hypotonia, spasticity, and complex movement disorders like ataxia / dystonia posses no challenges in regards to therapeutic approach, early initiation of ketogenic diet being accepted as standard of care. Atypical presentations with early onset absence seizures afebrile or not, abnormal eye movements, exercise induced dyskinesia/atonia, developmental involvement ranging from mild (temporary behavioral changes, postictal irritability and aggressivity) to severe (developmental arrest/ regression), posses the most difficult clinical dilemma. The normal rate of cerebral oxygen consumption is low during the fetal and perinatal periods; it then increases in a linear fashion to peak at the age 3 years, thereafter remaining high until adolescence when it shows a gradual decline. It is this critical period in which developing brain is more vulnerable to glucose deprivation and this is the period in which it is expected that mild presentations, unrecognized or untreated may have permanent consequences. Methods: We are presenting 3 clinical cases of GLUT1 DS, two of them with identified new mutations and a third one with phenotypic presentation of GLUT1 DS but with negative genetic screening. The therapeutic approach was different in each case and the rationale for each approach will be discussed Correlation with the 3D crystallographic structure was performed in one of the three cases. Results: The clinical characteristics of the 3 patients are presented in the table attached. CSF glucose and lactate are presented in 2 cases. One patient is on ketogenic diet and he is seizure free and medication free, and he shows much improvement in his developmental 1 year into treatment, but has persistent hyperactivity and persistent speech delay. The second patient had 6 febrile seizures with low-grade fever only. She continues to have normal development, but she is in the process of further genetic investigation. Treatment with triheptanoin was recommended. The third patient is on high dose of Keppra and modified Atkins diet with slow improvement in his autistic spectrum disorder symptoms and no clinical seizures. He is in the process of further genetic evaluation and whole exome sequencing is pending. Conclusions: GLUT 1DS phenotype is far from being fully characterized and genotype /phenotype correlation cannot be made in the initial stages of the disease. Structure analysis done in one case confirm that even a point mutation located outside of the channel can have pathogenic significance. A very high level of suspicion has to be maintained in clinical evaluation of patients presenting with paroxysmal events with or without seizures, both in early childhood and later in life. Early treatment should focus not only in controlling the seizures but to support development as well. An alternative energy substrate should be attempted knowing that there is a narrow safety margin for glucose transport across the blood?"brain barrier to meet the needs of brain metabolism and cerebral function. Similar to stroke approach this condition remind us that "time is brain" and we should treat it like a neurological emergency in order to avoid permanent damages. Funding: None