SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.

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.

Vaccine hesitancy among Saudi parents and its determinants. Result from the WHO SAGE working group on vaccine hesitancy survey tool.

OBJECTIVES: To assess the prevalence of vaccine hesitancy and its determinants among Saudi parents. In addition, we explored the relationship between vaccine hesitancy and child's immunization status. Methods: A cross-sectional study was conducted using interviews with parents visiting outpatient clinics at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, between July 2017 and October 2018. The strategic advisory group of experts on immunization vaccine hesitancy survey was used. Results: A total of 500 parents were interviewed. Twenty percent of parents were hesitant to get their child vaccinated. Parents with higher educational levels were more vaccine hesitant (p less than 0.001). Among parents who reported hesitancy toward vaccination, 36% of children were not vaccinated fully for their age. Concerns related to vaccine safety were the most frequent reason (53%) reported by vaccine-hesitant parents. Negative beliefs toward vaccination seemed to be associated with increase hesitancy and incomplete vaccination status of children. In multivariate analyses, the main factors associated with both parents' hesitancy and incomplete vaccination status were believing that vaccines are ineffective (adjusted odds ratio [AOR]=28, 95% confidence interval [CI]: 7.9-102.3) and believing that vaccines are not important (AOR=27, 95% CI: 5.8-126). Conclusion: Vaccine hesitancy among parents in Kingdom of Saudi Arabia is a concern and is likely to influence the vaccination status of their children. Countering vaccine related concerns must be tailored, particularly in higher-educated groups.