Abstracts

Rationale: There is a known association of SLC6A8[TCELMUW1]  mutations with epilepsy and Autism. We describe a case of a patient with medically refractory Epilepsy and Autism with a de novo likely pathogenic variant in  SLC6A8, c.1024T>C (p.W402R), that is  the cause of his epilepsy, cognitive impairment, and behavioral dysfunction. [TCELMUW1]Current gene nomenclature is to capitalize and italicize human genes, and just capitalize their associated protein Methods: Case report at Walter Reed National Military Medical Center and review of literature.. Results: The patient is a 42 year old man with a history of Autism and medically refractory Epilepsy who started to have seizures at 9 months old. Beginning in childhood the patient developed multiple seizure types including Absence seizures, tonic/atonic, complex partial seizures and generalized tonic-clonic seizures. He was also diagnosed with Autism and global developmental delay. His MRI brain was unremarkable. EEG demonstrated multifocal epileptiform discharges and right occipital onset subclinical seizures. He failed multiple AEDs before including Topamax, Dilantin, Depakote and Vimpat. He currently stays on Lamictal, Keppra, Gabatril and Klonopin. He still has 8-20 seizures per month. The patient had exome sequencing completed to his clinical history. A hemizygous SLC6A8variant, c.1024T>C (p.W402R)was identified. Both of his parents tested negative for this variant, confirming that it was de novo. This variant was interpreted as likely pathogenic and the cause of the patient’s symptoms. The patient had MR spectroscopy to detect Cr spikes in the brain and he was then started on creatine monohydrate, combined with L-arginine and L-glycine supplementation. Conclusions: SLC6A8 is an X-linked gene responsible for encoding the creatine transporter protein, and was discovered in 2001 to be a cause of intellectual disability and epilepsy.^1,2 Our case demonstrates a novel likely pathogenic variant in SLC6A8. Deficits in this transporter protein block creatine from being taken up by muscle and brain tissue. This is an important transporter because phosphocreatine, a creatine byproduct is needed for cellular activity within the brain and muscle, and neither muscle nor brain produce enough creatine independently.³ There are no clear approved therapies for this condition. Though there is some anecdotal and in vitro studies demonstrating a possible role for supplementation with arginine and glycine (creatine precursors which are not affected by this SLC6A8 mutation).² Additionally, in females there have been cases where supplementation with creatine reverses their symptoms.⁴ Although  this may happen because they are heterozygous and likely have some functional creatine transporters. Our case suggests that exome sequencing may shed new light in directing seizure management in certain patients with medically refractory epilepsy. Funding: No funding was received in support of this abstract.