BACKGROUND: ATP1A3 is a gene that encodes the ATPase Na + /K + transporting subunit alpha-3 isoenzyme that is widely expressed in GABAergic neurons. It maintains metabolic balance and neurotransmitter movement. These pathways are essential for the proper functioning of the nervous system. A mutation in the ATP1A3 gene demonstrates remarkable genotype-phenotype heterogeneity. OBJECTIVES: To provide insight into patients with ATP1A3 mutation. MATERIAL AND METHODS: These cases were identified using next generation sequencing. The patients' clinical and genetic data were retrieved. Detailed revision of the literature was conducted to illustrate and compare findings. The clinical, genetical, neuroimaging, and electrophysiological data of all pediatric patients were extracted. RESULTS: The study included 14 females and 12 males in addition to two novel females cases. Their mean current age is 6.3 ± 4.24 years. There were 11.54% preterm pregnancies with 5 cases reporting pregnancy complications. Mean age of seizure onset was 1.07 ± 1.06 years. Seizure semiology included generalized tonic-clonic, staring spells, tonic-clonic, and others. Levetiracetam was the most frequently used Anti-seizure medication. The three most frequently reported classical symptoms included alternating hemiplegia of childhood (50%), cerebellar ataxia (50%), and optic atrophy (23.08%). Non-classical symptoms included dystonia (73.08%), paroxysmal dyskinesias (34.62%), and encephalopathy (26.92%). Developmental delay was reported among 84.62% in cognitive, 92.31% in sensorimotor, 80.77% in speech, and 76.92% in socioemotional. EEG and MRI were non-specific. CONCLUSION: Our study demonstrated high heterogeneity among patients with pathogenic variants in the ATP1A3 gene. Such variation is multifactorial and can be a predisposition of wide genetic and clinical variables. Many patients shared few similarities in their genetic map including repeatedly reported de novo, heterozygous, mutations in the gene. Clinically, higher females prevalence of atypical presentation was noted. These findings are validated with prior evidence and the comprehensive analysis in this study.
Seizures , Sodium-Potassium-Exchanging ATPase , Male , Female , Infant, Newborn , Humans , Child , Infant , Child, Preschool , Phenotype , Mutation , Genotype , Sodium-Potassium-Exchanging ATPase/genetics
Background Sickle cell disease (SCD) is a common autosomal recessive inherited hemoglobin disorder in many countries. Neurological complications are among the most disabling complications in SCD. Stroke and cerebral vasculopathy can lead to further neurological insult. Ischemic insults, stroke, and silent infarcts are preventable causes of morbidity and mortality in SCD patients. Understanding the epidemiology and characteristics of such patients will help to prevent complications. Methodology This is a retrospective study conducted in a tertiary care center in Saudi Arabia. Cases of SCD admitted to the pediatric ward between the years 2019 to 2023 were included in the study. Demographic data, clinical diagnosis, and frequency of prior admissions were collected. Brain imaging results were reviewed and included. Furthermore, the study assessed common risk factors leading to developing a stroke in SCD pediatric patients. Risk factors and clinical outcomes after stroke were also included. Results Eighty-one patients were enrolled. The mean age of stroke patients was 8.21±3.50 years while the mean age of non-stroke patients was 6.24±3.76 years. More than half of the patients were females in both the stroke (61.50%) and non-stroke groups (52.90%). Thirteen SCD patients (16%) were diagnosed with stroke. Previous history of stroke, high mean corpuscular volume (MCV), and low red blood cells count (RBC) were statistically significant risk factors for stroke (p<0.0001), (p<0.0001), (p<0.03), respectively. Conclusion Stroke is one of the most devastating complications of SCD. The prevalence of stroke among SCD patients in our study was 16%. Transcranial Doppler ultrasound screening is the most important predictor of stroke.
