Incidence of Inborn Errors of Metabolism and Endocrine Disorders Among 40965 Newborn Infants at Riyadh Second Health Cluster of the Ministry of Health Saudi Arabia.

Inborn errors of metabolism (IEM) and endocrine disorders are common genetic conditions in the Saudi population with the incidence rate often underestimated. Newborn screening (NBS) using various disease panels provides the first line in the early detection and intervention among infants with a high risk of IEM. Here we aim to assess the incidence of screening disorders and provide an overview of the NBS program at the Ministry of Health Tertiary Care King Fahad Medical City.

Exploring the self-efficacy of patients with diabetes: its role as a predictor of diabetes management and well-being.

Background: Self-efficacy is a popular psychological concept that refers to an individual's perception or belief in his ability to perform specific actions. This study aimed to assess the predictive value of self-efficacy, measured using the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SEM6S) questionnaire, for diabetes management and overall well-being in patients with diabetes.

Subject And Methods: An anonymous online cross-sectional study was conducted to evaluate the self-efficacy of diabetic patients in the Asser region of Saudi Arabia.

Clinical and Molecular Characteristics of Neuronal Ceroid Lipofuscinosis in Saudi Arabia.

Background: Neuronal ceroid lipofuscinoses (NCLs) represent a heterogeneous group of inherited metabolic lysosomal disorders characterized by neurodegeneration. This study sought to describe the clinical and molecular characteristics of NCLs in Saudi Arabia and determine the most common types in that population.

Methods: A retrospective review of electronic medical records was conducted for 63 patients with NCL (55 families) from six tertiary and referral centers in Saudi Arabia between 2008 and 2022.

Development of simple and effective PCR based assay to detect mutation (c.425G > A) among Saudi carriers and functional study of the homozygous mutations.

The aim of this study is to develop a rapid and effective method to screen for Saudi carriers of one of the most common propionic acidemia mutations (c.425G > A) and to study the functional impact of this mutation. Using allele-specific primers, we have developed a qPCR assay that clearly distinguishes heterozygotes from mutated and wild type homozygotes that overcome the dependence on labor-intensive gene sequencing.

A reverse genetics and genomics approach to gene paralog function and disease: Myokymia and the juxtaparanode.

The leucine-rich glioma-inactivated (LGI) family consists of four highly conserved paralogous genes, LGI1-4, that are highly expressed in mammalian central and/or peripheral nervous systems. LGI1 antibodies are detected in subjects with autoimmune limbic encephalitis and peripheral nerve hyperexcitability syndromes (PNHSs) such as Isaacs and Morvan syndromes. Pathogenic variations of LGI1 and LGI4 are associated with neurological disorders as disease traits including familial temporal lobe epilepsy and neurogenic arthrogryposis multiplex congenita 1 with myelin defects, respectively.

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.

Succinyl-CoA:3-oxoacid coenzyme A transferase (SCOT) deficiency: A rare and potentially fatal metabolic disease.

Succinyl-CoA:3-oxoacid coenzyme A transferase deficiency (SCOTD) is a rare autosomal recessive disorder of ketone body utilization caused by mutations in OXCT1. We performed a systematic literature search and evaluated clinical, biochemical and genetic data on 34 previously published and 10 novel patients with SCOTD. Structural mapping and in silico analysis of protein variants is also presented.

Categorized Genetic Analysis in Childhood-Onset Cardiomyopathy.

Background: Childhood-onset cardiomyopathy is a heterogeneous group of conditions the cause of which is largely unknown. The influence of consanguinity on the genetics of cardiomyopathy has not been addressed at a large scale.

Methods: To unravel the genetic cause of childhood-onset cardiomyopathy in a consanguineous population, a categorized approach was adopted.

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids.

Bi-allelic Variants in IQSEC1 Cause Intellectual Disability, Developmental Delay, and Short Stature.

We report two consanguineous families with probands that exhibit intellectual disability, developmental delay, short stature, aphasia, and hypotonia in which homozygous non-synonymous variants were identified in IQSEC1 (GenBank: NM_001134382.3). In a Pakistani family, the IQSEC1 segregating variant is c.

Spectrum of mutations underlying Propionic acidemia and further insight into a genotype-phenotype correlation for the common mutation in Saudi Arabia.

Propionic acidemia (PA) is an autosomal recessive metabolic disorder. PA is characterized by deficiency of the mitochondrial enzyme propionyl CoA carboxylase (PCC) that results in the accumulation of propionic acid. Alpha and beta subunits of the PCC enzyme are encoded by the and genes, respectively.

Widening the phenotypic spectrum - Non epileptic presentation of folate transporter deficiency.

Introduction: Folate is essential for production of DNA, neurotransmitters and myelin and regulation of genetic activity. A specific transporter protein is required to transport folate from blood to CSF. Various inherited brain-specific folate transport defects have been recognized due to mutation in Folate Receptor alpha (FOLR1).

FARS2 deficiency; new cases, review of clinical, biochemical, and molecular spectra, and variants interpretation based on structural, functional, and evolutionary significance.

An increasing number of mitochondrial diseases are found to be caused by pathogenic variants in nuclear encoded mitochondrial aminoacyl-tRNA synthetases. FARS2 encodes mitochondrial phenylalanyl-tRNA synthetase (mtPheRS) which transfers phenylalanine to its cognate tRNA in mitochondria. Since the first case was reported in 2012, a total of 21 subjects with FARS2 deficiency have been reported to date with a spectrum of disease severity that falls between two phenotypes; early onset epileptic encephalopathy and a less severe phenotype characterized by spastic paraplegia.

Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.

Fucosyltransferase 8 (FUT8) encodes a Golgi-localized α1,6 fucosyltransferase that is essential for transferring the monosaccharide fucose into N-linked glycoproteins, a process known as "core fucosylation." Here we describe three unrelated individuals, who presented with intrauterine growth retardation, severe developmental and growth delays with shortened limbs, neurological impairments, and respiratory complications. Each underwent whole-exome sequencing and was found to carry pathogenic variants in FUT8.

Molecular and clinical spectra of FBXL4 deficiency.

F-box and leucine-rich repeat protein 4 (FBXL4) is a mitochondrial protein whose exact function is not yet known. However, cellular studies have suggested that it plays significant roles in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) maintenance, and mitochondrial dynamics. Biallelic pathogenic variants in FBXL4 are associated with an encephalopathic mtDNA maintenance defect syndrome that is a multisystem disease characterized by lactic acidemia, developmental delay, and hypotonia.

Excessive homozygosity identified by chromosomal microarray at a known GCDH mutation locus correlates with brain MRI abnormalities in an infant with glutaric aciduria.

Herein, we report a conceptually novel clinical case highlighting the diagnostic implications of excessive homozygosity and its correlation with brain MRI abnormalities in an infant with GA1. The case also points a need for an extra amount of caution to be exercised when evaluating patients with "negative exomes."

Exome sequencing in mostly consanguineous Arab families with neurologic disease provides a high potential molecular diagnosis rate.

Background: Neurodevelopment is orchestrated by a wide range of genes, and the genetic causes of neurodevelopmental disorders are thus heterogeneous. We applied whole exome sequencing (WES) for molecular diagnosis and in silico analysis to identify novel disease gene candidates in a cohort from Saudi Arabia with primarily Mendelian neurologic diseases.

Methods: We performed WES in 31 mostly consanguineous Arab families and analyzed both single nucleotide and copy number variants (CNVs) from WES data.

Monoallelic and Biallelic Variants in EMC1 Identified in Individuals with Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy.

The paradigm of a single gene associated with one specific phenotype and mode of inheritance has been repeatedly challenged. Genotype-phenotype correlations can often be traced to different mutation types, localization of the variants in distinct protein domains, or the trigger of or escape from nonsense-mediated decay. Using whole-exome sequencing, we identified homozygous variants in EMC1 that segregated with a phenotype of developmental delay, hypotonia, scoliosis, and cerebellar atrophy in three families.

ADAT3-related intellectual disability: Further delineation of the phenotype.

ADAT3-related intellectual disability has been recently described in 24 individuals from eight Saudi families who had cognitive impairment and strabismus. Other common features included growth failure, microcephaly, tone abnormalities, epilepsy, and nonspecific brain abnormalities. A single homozygous founder mutation (c.

ISCA2 mutation causes infantile neurodegenerative mitochondrial disorder.

Background: There are numerous nuclear genes that cause mitochondrial disorders and clinically and genetically heterogeneous disorders whose aetiology often remains unsolved. In this study, we aim to investigate an autosomal recessive syndrome causing leukodystrophy and neuroregression. We studied six patients from five unrelated consanguineous families.

Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance.

Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, and the molecular etiology remains undiagnosed in the majority of cases. Through whole-exome sequencing, we identified recessive nonsense and splicing mutations in FBXL4 segregating in three unrelated consanguineous kindreds in which affected children present with a fatal encephalopathy, lactic acidosis, and severe mtDNA depletion in muscle. We show that FBXL4 is an F-box protein that colocalizes with mitochondria and that loss-of-function and splice mutations in this protein result in a severe respiratory chain deficiency, loss of mitochondrial membrane potential, and a disturbance of the dynamic mitochondrial network and nucleoid distribution in fibroblasts from affected individuals.

Prescribing patterns for acute respiratory infections in primary health care, aseer region, saudi arabia.

Objective: The objective of this study was to identify the patterns of prescribing for Acute respiratory infections in patients attending primary health care centers in the Aseer region, southwestern Saudi Arabia. MATERIALS #ENTITYSTARTX00026;

Methods: This study was conducted at primary health care centers in the Aseer region during November 2003. A master sheet designed by the investigator was distributed to all the working physicians in the primary health care center in the Aseer region.

Goldenhar syndrome and hereditary tyrosinemia type 1.

We report a case of Goldenhar syndrome and hereditary tyrosinemia type 1 (HTT1), to our knowledge an association not previously described. This case further increases the diversity of observations and clinical descriptions of patients with this complex syndrome. We discuss pathogenetic aspects, and demonstrate further evidence of the effectiveness of 2-(2-nitro-4-trifluoromethyl benzoyl)-1,3-cyclohexanedione in the treatment of HTT1.