Method Development and Clinical Utility for Simultaneous Measurement of 21-Deoxycortisol, 17-Hydroxyprogesterone, Cortisol, and Cortisone Levels in Human Plasma Using UHPLC-MS/MS.

A simple and efficient validated assay for quantifying 21-deoxycortisol (21-DOC), 17-hydroxyprogesterone (17-OHP), cortisol, and cortisone in human plasma has been developed using ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Analysis of plasma samples were performed on Atlantis dC18 (3 m) column using a mobile phase of 20.0 mM ammonium acetate and acetonitrile (50:50, : ) that was delivered at isocratic flow rate 0.

Case report: Clinical and genetic characterization of a novel variant causing pyridoxine-dependent epilepsy, developmental delay, and intellectual disability in two siblings.

Background: Pathogenic variants in are associated with pyridoxine-dependent epilepsy (PDE), a rare autosomal recessive disorder characterized by epileptic seizures, unresponsiveness to standard antiseizure medications (ASM), and a response only to pyridoxine. Here, we report two patients (from a consanguineous family) with neonatal seizures and developmental delay.

Case Presentation: Patient 1 (a 13-year-old girl) was born normally at term.

Role of age and sex in the incidence of adverse effects among diabetic patients treated with glipizide.

Glipizide is an antidiabetic drug that belongs to a class of medication known as sulfonylureas. It is considered one of the highly prescribed antidiabetic drugs for the treatment of type II diabetes in patients following a kidney transplant. It lowers blood glucose levels by causing the release of insulin from β-cells in the pancreas.

Is there a relationship between low back pain and ligamentum flavum hypertrophy?

Objective: A condition known as ligamentum flavum (LF) hypertrophy occurs when the ligamentum flavum (LF) swells as a result of pressures applied to the spine. Among the elderly population, lumbar spinal stenosis is a major cause of pain and disabilities. Numerous studies indicate that lumbar spinal stenosis etiology involves the ligamentum flavum in a major way.

Exploratory Untargeted Metabolomics of Dried Blood Spot Samples from Newborns with Maple Syrup Urine Disease.

Currently, tandem mass spectrometry-based newborn screening (NBS), which examines targeted biomarkers, is the first approach used for the early detection of maple syrup urine disease (MSUD) in newborns, followed by confirmatory genetic mutation tests. However, these diagnostic approaches have limitations, demanding the development of additional tools for the diagnosis/screening of MUSD. Recently, untargeted metabolomics has been used to explore metabolic profiling and discover the potential biomarkers/pathways of inherited metabolic diseases.

Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots.

Galactosemia (GAL) is a genetic disorder that results in disturbances in galactose metabolism and can lead to life-threatening complications. However, the underlying pathophysiology of long-term complications in GAL remains poorly understood. In this study, a metabolomics approach using ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was used to investigate metabolomic changes in dried blood spots of 15 patients with GAL and 39 healthy individuals.

Clinical, radiological, and genetic characterization of variants in Saudi families: Genotype phenotype correlation and brief review of the literature.

Background: (solute carrier family 13, member 5) encodes sodium/citrate cotransporter, which mainly localizes in cellular plasma membranes in the frontal cortex, retina, and liver. Pathogenic variants of the gene cause an autosomal recessive syndrome known as "developmental and epileptic encephalopathy 25 with amelogenesis imperfecta."

Results: Here, we have investigated six patients from three different consanguineous Saudi families.

Lipidomics Profiling of Patients with Low Bone Mineral Density (LBMD).

The relationship between lipid metabolism and bone mineral density (BMD) is still not fully elucidated. Despite the presence of investigations using osteoporotic animal models, clinical studies in humans are limited. In this work, untargeted lipidomics profiling using liquid chromatography-mass spectrometry (LC-MS) analysis of human serum samples was performed to identify the lipidomics profile associated with low bone mineral density (LBMD), with a subsequent examination of potential biomarkers related to OP risk prediction or progression.

Characterization of variants of uncertain significance in isovaleryl-CoA dehydrogenase identified through newborn screening: An approach for faster analysis.

Introduction: Clinical standard of care for newborn screening (NBS) is acylcarnitine metabolites quantitation by tandem mass spectrometry (MS/MS) from dried blood spots. Follow up sequencing often results in identification of one or more variants of uncertain significance (VUS). Isovaleric acidemia (IVA) is an autosomal recessive inborn error of metabolism caused by deficiency of isovaleryl-CoA dehydrogenase (IVDH) in the Leu catabolism pathway.

Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41.

Physiological Perspectives on the Use of Triheptanoin as Anaplerotic Therapy for Long Chain Fatty Acid Oxidation Disorders.

Inborn errors of mitochondrial fatty acid oxidation (FAO) comprise the most common group of disorders identified through expanded newborn screening mandated in all 50 states in the United States, affecting 1:10,000 newborns. While some of the morbidity in FAO disorders (FAODs) can be reduced if identified through screening, a significant gap remains between the ability to diagnose these disorders and the ability to treat them. At least 25 enzymes and specific transport proteins are responsible for carrying out the steps of mitochondrial fatty acid metabolism, with at least 22 associated genetic disorders.

Incidence of newborn screening disorders among 56632 infants in Central Saudi Arabia. A 6-year study.

Objectives: To determine the incidence of newborn screening (NBS) disorders and to study the key performance indicators of the program.

Methods: This retrospective single-center study enrolled all infants who underwent NBS from January 2012 to December 2017 at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. We screened 17 NBS disorders.

Clinical, biochemical, mitochondrial, and metabolomic aspects of methylmalonate semialdehyde dehydrogenase deficiency: Report of a fifth case.

Methylmalonate semialdehyde dehydrogenase deficiency (MMSDD; MIM 614105) is a rare autosomal recessive defect of valine and pyrimidine catabolism. Four prior MMSDD cases are published. We present a fifth case, along with functional and metabolomic analysis.

Rett Syndrome, a Neurodevelopmental Disorder, Whole-Transcriptome, and Mitochondrial Genome Multiomics Analyses Identify Novel Variations and Disease Pathways.

Rett syndrome (RTT) is a severe neurodevelopmental disorder reported worldwide in diverse populations. RTT is diagnosed primarily in females, with clinical findings manifesting early in life. Despite the variable rates across populations, RTT has an estimated prevalence of ∼1 in 10,000 live female births.

Targeted SLC19A3 gene sequencing of 3000 Saudi newborn: a pilot study toward newborn screening.

Background: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive neurometabolic disorder mostly presented in children. The disorder is described as having subacute encephalopathy with confusion, dystonia, and dysarthria triggered by febrile illness that leads to neuroregression and death if untreated. Using biotin and thiamine at an early stage of the disease can lead to significant improvement.

First report of two successive deletions on chromosome 15q13 cytogenetic bands in a boy and girl: additional data to 15q13.3 syndrome with a report of high IQ patient.

15q13.3 syndrome is associated with a wide spectrum of neurological disorders. Among a cohort of 150 neurodevelopmental cases, we identified two patients with two close proximity interstitial hemizygous deletions on chromosome 15q13.

The Prevalence of Phenylketonuria in Arab Countries, Turkey, and Iran: A Systematic Review.

Background/objectives: This paper seeks to identify the prevalence of Phenylketonuria (PKU) in Arab countries, Turkey, and Iran. The study reviewed the existence of comprehensive national newborn screening programs and reported consanguinity rates.

Methods: A computer based literature search was conducted using relevant keywords to retrieve studies conducted on PKU.

Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis.

Context: Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, affecting one in 3000 to 4000 newborns. Since the introduction of a newborn screening program in 1988, more than 300 cases have been identified. The underlying genetic defects have not been systematically studied.

A Novel Homozygous Mutation in SPTBN2 Leads to Spinocerebellar Ataxia in a Consanguineous Family: Report of a New Infantile-Onset Case and Brief Review of the Literature.

The objective of this study was the identification of likely genes and mutations associated with an autosomal recessive (AR) rare spinocerebellar ataxia (SCA) phenotype in two patients with infantile onset, from a consanguineous family. Using genome-wide SNP screening, autozygosity mapping, targeted Sanger sequencing and nextgen sequencing, family segregation analysis, and comprehensive neuropanel, we discovered a novel mutation in SPTBN2. Next, we utilized multiple sequence alignment of amino acids from various species as well as crystal structures provided by protein data bank (PDB# 1WYQ and 1WJM) to model the mutation site and its effect on β-III-spectrin.

Expanded Newborn Screening Program in Saudi Arabia: Incidence of screened disorders.

Aim: To address the implementation of the National Newborn Screening Program (NBS) in Saudi Arabia and stratify the incidence of the screened disorders.

Methods: A retrospective study conducted between 1 August 2005 and 31 December 2012, total of 775 000 newborns were screened from 139 hospitals distributed among all regions of Saudi Arabia. The NBS Program screens for 16 disorders from a selective list of inborn errors of metabolism (IEM) and endocrine disorders.

Whole-exome sequencing identifies novel variants in PNPT1 causing oxidative phosphorylation defects and severe multisystem disease.

Recent advances in next-generation sequencing strategies have led to the discovery of many novel disease genes. We describe here a non-consanguineous family with two affected boys presenting with early onset of severe axonal neuropathy, optic atrophy, intellectual disability, auditory neuropathy and chronic respiratory and gut disturbances. Whole-exome sequencing (WES) was performed on all family members and we identified compound heterozygous variants (c.

Assessment of the Knowledge and Attitudes of Saudi Mothers towards Newborn Screening.

Objective: To assess the attitude and knowledge of the Saudi mothers toward newborn screening (NBS) program.

Methods: A total of 425 Saudi women (only mothers who have at least one pregnancy) participated in the study from different regions in Saudi Arabia and completed the structured questionnaire which sought their views on the NBS services.

Results: A majority of the participating women (91.

Utility of next-generation sequencing technologies for the efficient genetic resolution of haematological disorders.

Next-generation sequencing (NGS) has now evolved to be a relatively affordable and efficient means of detecting genetic mutations. Whole genome sequencing (WGS) or whole exome sequencing (WES) offers the opportunity for rapid diagnosis in many paediatric haematological conditions, where phenotypes are variable and either a large number of genes are involved, or the genes are large making sanger sequencing expensive and labour-intensive. NGS offers the potential for gene discovery in patients who do not have mutations in currently known genes.

Inherited bone marrow failure associated with germline mutation of ACD, the gene encoding telomere protein TPP1.

Telomerase is a ribonucleoprotein enzyme that is necessary for overcoming telomere shortening in human germ and stem cells. Mutations in telomerase or other telomere-maintenance proteins can lead to diseases characterized by depletion of hematopoietic stem cells and bone marrow failure (BMF). Telomerase localization to telomeres requires an interaction with a region on the surface of the telomere-binding protein TPP1 known as the TEL patch.