The uptake and efflux of solutes across a plasma membrane is controlled by transporters. There are two main superfamilies of transporters,
adenosine 5'-triphosphate (
ATP) binding cassettes (ABCs) and solute carriers (SLCs). In the brain, SLC transporters are involved in transporting various solutes across the blood-brain barrier, blood-cerebrospinal fluid barrier, astrocytes, neurons, and other brain cell types including oligodendrocytes and microglial cells. SLCs play an important role in maintaining normal brain function. Hence, mutations in the genes that encode SLC transporters can cause a variety of
neurological disorders. We identified the following SLC gene variants in 25 patients in our cohort: SLC1A2, SLC2A1, SLC5A1, SLC6A3, SLC6A5, SLC6A8, SLC9A6, SLC9A9, SLC12A6, SLC13A5, SLC16A1, SLC17A5, SLC19A3, SLC25A12, SLC25A15, SLC27A4, SLC45A1, SLC46A1, and SLC52A3. Eight patients harbored pathogenic or likely pathogenic mutations (SLC5A1, SLC9A6, SLC12A6, SLC16A1, SLC19A3, and SLC52A3), and 12 patients were found to have variants of unknown clinical significance (VOUS); these variants occurred in 11 genes (SLC1A2, SLC2A1, SLC6A3, SLC6A5, SLC6A8, SLC9A6, SLC9A9, SLC13A5, SLC25A12, SLC27A4, and SLC45A1). Five patients were excluded as they were carriers. In the remaining 20 patients with SLC gene variants, we identified 16 possible distinct
neurological disorders. Based on the clinical presentation, we categorized them into genes causing intellectual delay (ID) or
autism spectrum disorder (ASD), those causing
epilepsy, those causing
vitamin-related disorders, and those causing other neurological diseases. Several variants were detected that indicated possible personalized
therapies: SLC2A1 led to
dystonia or
epilepsy, which can be treated with a
ketogenic diet; SLC6A3 led to
infantile parkinsonism-dystonia 1, which can be treated with
levodopa; SLC6A5 led to
hyperekplexia 3, for which unnecessary treatment with
antiepileptic drugs should be avoided; SLC6A8 led to
creatine deficiency syndrome type 1, which can be treated with
creatine monohydrate; SLC16A1 led to monocarboxylate transporter 1 deficiency, which causes
seizures that should not be treated with a
ketogenic diet; SLC19A3 led to
biotin-
thiamine-responsive
basal ganglia disease, which can be treated with
biotin and
thiamine; and SLC52A3 led to
Brown-Vialetto-Van-Laere syndrome 1, which can be treated with
riboflavin. The present study examines the prevalence of SLC gene mutations in our cohort of children with
epilepsy and other
neurological disorders. It highlights the diverse phenotypes associated with mutations in this large family of SLC transporter
proteins, and an opportunity for personalized genomics and personalized
therapeutics.