Childhood-related neural genotype-phenotype in ATP1A3 mutations: comprehensive analysis.

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.

GAMT Deficiency Among Pediatric Population: Clinical and Molecular Characteristics and Management.

Objective: Analyze the treatment modalities used in real practice by synthesizing available literature. Methods: We reviewed and evaluated 52 cases of GAMT deficiency including 4 novel cases from Saudi Arabia diagnosed using whole-exome sequencing. All data utilized graphical presentation in the form of line charts and illustrated graphs. Results: The mean current age of was 117 months (±29.03) (range 12-372 months). The mean age of disease onset was 28.32 months (±13.68) (range 8 days - 252 months). The most prevalent symptom was developmental delays, mainly speech and motor, seizures, and intellectual disability. The male-to-female ratio was 3:1. Multiple treatments were used, with 54 pharmacological interventions, valproic acid being the most common. Creatinine monohydrate was the prevalent dietary intervention, with 25 patients reporting an improvement. Conclusion: The study suggests that efficient treatment with appropriate dietary intervention can improve patients' health, stressing that personalized treatment programs are essential in managing this disorder.

Accuracy of Ultrasound and Computed Tomography in Diagnosing Acute Cholecystitis Patients in a Tertiary Care Center in Saudi Arabia.

Background Acute cholecystitis (AC) is a gallbladder inflammatory disease often associated with gallbladder stones. It accounts for up to 5% of emergency department visits. The majority of patients present with pain in the right upper quadrant, Murphy's sign, and fever. Furthermore, Saudi Arabia has been noted to have a significant prevalence of AC. According to the 2018 Tokyo Guidelines, imaging is an essential element, combined with local and systemic evidence of inflammation, for a confirmed diagnosis of AC. The definitive therapy is conducted surgically by cholecystectomy either urgently or electively. However, there are insufficient studies that focus on the accuracy of imaging in diagnosing AC patients in Saudi Arabia. Objective The aim of this study is to assess the accuracy of ultrasound (US) versus computed tomography (CT) in diagnosing AC patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. Methods and material A retrospective record review was conducted at KAUH during the period of June to July 2022. The study included 192 patients diagnosed with AC in the emergency department or outpatient department by US or CT or both and confirmed by laparoscopic cholecystectomy and histopathology between 2016 and 2022. Results The most common modality used was US (79.7%), followed by both US and contrast CT (10.9%). For CT, sensitivity was 81.3%, specificity was 62.5%, positive predictive value (PPV) was 59.1%, and negative predictive value (NPV) was 83.3%. For US, sensitivity was 37.9%, specificity was 81.7%, PPV was 50%, and NPV was 73.1%. A significant relationship was observed between both genders and high use of US (P = 0.0001). Conclusion We found that CT is more sensitive than US, while US is more specific in diagnosing AC.