Abstracts

Rationale: SLC2A1 is a gene coding for the main glucose transporter (GLUT1) across the blood-brain barrier. There is a spectrum of epileptic syndromes associated with mutations in the SLC2A1 gene. Here we describe a patient with a new variant of SLC2A1 gene resulting in an atypical phenotype of GLUT1 Deficiency Syndrome (GLUT1DS) with myoclonic-astatic seizures and the associated EEG. Methods: Patient is the product of non-consanguineous parents with uncomplicated full-term pregnancy and delivery. Seizures started at the age of two weeks with episodes of rhythmic left sided jerking and rapid irregular eye movements and blinking. At the age of three she started having frequent episodes of atonic seizures and staring spells, occasionally generalized, and refractory to escalating mediations. Intellectual impairment became more evident by the age of four. EEG progressively worsened with frequent epileptiform discharges and encephalopathy. A gene panel revealed a missense mutation in the SLC2A1 gene of uncertain significance. GLUT1DS was suspected. Further work-up revealed a low CSF fasting glucose of 52 with a CSF:serum glucose ratio of 0.6. Patient was referred for ketogenic diet. Results: GLUT1DS represents a spectrum of disease with varying degrees of severity. Fasting hypoglycorrhachia is the most important lab observation with all patients reported to have a value of less than 60 mg/dl. The classic phenotype is described with seizures prior to age of two, delayed neurological development, microcephaly, hypotonia, and complex movement disorders. Seizure semiology vary with atonic being relatively rare. Approximately 70-80% of patients with GLUT1DS have mutation of the SLC2A1 gene, all being heterozygous. In 2007, 54 mutations were identified, and more are currently being recognized and reported in the literature.Our patient had a borderline CSF to serum glucose ratio at 0.6 as well as absence of classic movement disorders and microcephaly. Her progressively worsening EEG and refractory epilepsy along with worsening neurodevelopment and hypotonia prompted further work-up for genetic epilepsy syndromes. An unrecognized mutation of the SLC2A1 gene with replacement of glycine with tryptophan at codon 470 was found; the significance of which was uncertain as it has not been reported in the literature. That in the context of reduced fasting CSF glucose and the described clinical syndrome prompted the diagnosis of GLUT1DS and initiating the appropriate treatment. Genetic testing of the parents can further support the diagnosis and illicit inheritance. Conclusions: Diagnosis of GLUT1 DS can be challenging due to increasing complexity of the clinical phenotypes as well as the genetic heterogeneity. The early recognition of the clinical spectrum as well as genetic testing is imperative since it is a potentially treatable condition with ketogenic diet significantly improving quality of life. The EEG findings may be focal and evolve over time. Reporting previously unrecognized mutations helps reduce the chances of missing the diagnosis. Funding: No funding