Genetic Microcephaly in a Saudi Population: Unique Spectrum of Affected Genes Including a Novel One.

Genetic microcephaly is linked to an increased risk of developmental disabilities, epilepsy, and motor impairment. The aim of this study is to describe the spectrum of identifiable genetic etiologies, clinical characteristics, and radiologic features of genetic microcephaly in patients referred to a tertiary center in Saudi Arabia. This is a retrospective chart review study of all patients with identifiable genetic microcephaly presenting to a tertiary center in Saudi Arabia.

Effectiveness of intra-thecal methotrexate in refractory Anti-N-methyl-d-aspartate receptor encephalitis.

Background: Anti-N-methyl-d-aspartate "anti-NMDA" receptor encephalitis is one of the most common autoimmune encephalitis for which first- and second-line therapies have been recommended following international consensus. However, some refractory cases do not respond to the first- and second-line therapy and require further immune-modulatory therapies such as intra-thecal methotrexate. In this study, we reviewed six confirmed cases of refractory anti-NMDA receptor encephalitis from two tertiary centers in Saudi Arabia that required escalation of treatment and received a six-month course of intra-thecal methotrexate.

Clinical Characteristics and Risk Factors of Neonatal Hypoxic-Ischaemic Encephalopathy and Its Associated Neurodevelopmental Outcomes During the First Two Years of Life: A Retrospective Study in Saudi Arabia.

Objective: This study aimed to determine the clinical characteristics and factors associated with neonatal hypoxic-ischaemic encephalopathy (HIE) and its neurodevelopmental outcomes.

Methods: We conducted retrospective case-control research to investigate the clinical and labour-related risk factors for HIE. In addition, a single-centre cohort study was conducted on infants with HIE to describe their neurodevelopment from birth to 24 months.

Pediatrics COVID-19 and neurological manifestations: Single tertiary centre experience.

Importance: Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome that is caused by a novel coronavirus 2 (SARS-CoV-2). It originated in China late December 2019 and was declared a global pandemic on March 12, 2020. Most reports of COVID-19 cases either presented with neurological manifestations or complications involve adults.

The Leukodystrophy Spectrum in Saudi Arabia: Epidemiological, Clinical, Radiological, and Genetic Data.

Leukodystrophies (LDs) are inherited heterogeneous conditions that affect the central nervous system with or without peripheral nerve involvement. They are individually rare, but collectively, they are common. Thirty disorders were included by the Global Leukodystrophy Initiative Consortium (GLIA) as LDs.

Acute Necrotizing Encephalopathy of Childhood: A Multicenter Experience in Saudi Arabia.

Acute necrotizing encephalopathy of childhood (ANEC) is a rapidly progressing encephalopathy characterized by fever, depressed level of consciousness, and seizures. Diagnosis depends on clinical presentation and characteristic neuroimaging findings of abnormal signal intensity involving the thalami as well as the supra and infra-tentorial areas. Treatment modalities are not well-established; empirical treatment with antibiotics and antiviral agents is the initial step, followed by steroids and immunoglobulin, as well as supportive care.

Biallelic loss-of-function variants in NEMF cause central nervous system impairment and axonal polyneuropathy.

We aimed to detect the causative gene in five unrelated families with recessive inheritance pattern neurological disorders involving the central nervous system, and the potential function of the NEMF gene in the central nervous system. Exome sequencing (ES) was applied to all families and linkage analysis was performed on family 1. A minigene assay was used to validate the splicing effect of the relevant discovered variants.

EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay.

In recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID. Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders.

Genomic testing and counseling: The contribution of next-generation sequencing to epilepsy genetics.

Introduction: Currently, next-generation sequencing (NGS) technology is more accessible and available to detect the genetic causation of diseases. Though NGS technology benefited some clinical phenotypes, for some clinical diagnoses such as seizures and epileptic disorders, adaptation occurred slowly. The genetic diagnosis was mainly based on epilepsy gene panels and not on whole exome and/or genome sequencing.

Epilepsy in Propionic Acidemia: Case Series of 14 Saudi Patients.

Propionic acidemia is an inborn error of metabolism that is inherited in an autosomal recessive manner. It is characterized by a deficient propionyl-CoA carboxylase due to mutations in either of its beta or alpha subunits. In the literature, there is a clear association between propionic acidemia and epilepsy.

Further Delineation of the Clinical Phenotype of Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome Type 4.

Background: Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a heterogeneous group of genetic disorders that have been grouped by shared clinical features; all of these features are transmitted via an autosomal recessive mechanism. Four variants of this syndrome have been identified so far, and each one differs in terms of both clinical and genotypical features. CAMRQ4 is a rare genetic disorder characterized by mental retardation, ataxia or an inability to walk, dysarthria and, in some patients, quadrupedal gait.

Retrospective review of pediatric status epilepticus in 116 Saudi patients: predictors of outcome.

Background: Status epilepticus (SE) is a common, life-threatening condition. Multiple factors are used to predict its outcome and evaluate its risks, and there have been only a few studies in Saudi Arabia.

Objectives: Investigate predictors of SE outcome.

Further delineation of the phenotypic spectrum of ISCA2 defect: A report of ten new cases.

Iron-Sulfur Cluster (ISC) biogenesis is a vital cellular process required to produce various ISC-containing proteins. These ISC proteins are responsible for essential functions such as glycine cleavage and the formation of lipoic acid, an essential cofactor of respiratory chain complexes. Defects in ISC biogenesis lead to multiple mitochondrial dysfunction syndromes including: ISCA2 with infantile onset leukodystrophy.

Mutation in SLC6A9 encoding a glycine transporter causes a novel form of non-ketotic hyperglycinemia in humans.

Glycine cleavage system (GCS) catalyzes the degradation of glycine and disruption of its components encoded by GLDC, AMT and GCSH are the only known causes of glycine encephalopathy, also known as non-ketotic hyperglycinemia (NKH). In this report, we describe a consanguineous family with one child who presented with NKH, but harbored no pathogenic variants in any of the three genes linked to this condition. Whole-exome sequencing revealed a novel homozygous missense variant in exon 9 of SLC6A9 NM_201649.

Worsening of Seizures After Asparagine Supplementation in a Child with Asparagine Synthetase Deficiency.

Objective: Asparagine synthetase deficiency is an autosomal recessive neurometabolic disorder characterized clinically by severe congenital microcephaly, global developmental delay, intractable epilepsy, and motor impairment in the form of spastic quadriparesis. Diagnosis is confirmed by findings of low cerebral spinal fluid or plasma asparagine in addition to a mutation of the subsequently in ASNS gene. There is no documented trial of asparagine as a treatment for this disorder.

Asparagine Synthetase Deficiency: New Inborn Errors of Metabolism.

Background: Asparagine synthetase deficiency (ASD) is a newly identified neurometabolic disorder characterized by severe congenital microcephaly, severe global developmental delay, intractable seizure disorder, and spastic quadriplegia. Brain MRI showed brain atrophy, delayed myelination, and simplified gyriform pattern.

Methods: We report ASD deficiency in a 2- and 4-year-old sibling.

Hereditary neurometabolic causes of infantile spasms in 80 children presenting to a tertiary care center.

Background: Infantile spasms are a devastating infantile epileptic syndrome with multiple etiologies. Hereditary neurometabolic disorders are rarely recognized causes of infantile spasms. The aim of this study was to identify hereditary neurometabolic disorders when they were the cause of infantile spasms in patients presenting to a tertiary care center in Saudi Arabia.

Pseudotumor cerebri in a child receiving peritoneal dialysis: Recovery of vision after lumbo-pleural shunt.

A 9-year-old boy with end-stage renal disease who was receiving continuous ambulatory peritoneal dialysis (CAPD) presented with acute visual loss and was found to have papilledema. Neuroimaging and cerebrospinal fluid (CSF) analysis were normal. The lumbar puncture opening pressure was 290 mm of water so the diagnosis of pseudotumor cerebri (PTC) was entertained.