26,717 results match your criteria inborn errors

Screening for inborn errors of metabolism in psychotic patients using Next Generation Sequencing.

J Psychiatr Res 2021 Apr 1;138:125-129. Epub 2021 Apr 1.

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Faculty of Health and Life Sciences (FHML), Maastricht University, Maastricht, the Netherlands.

Inborn errors of metabolism (IEMs) are a group of rare genetic disorders which, when emerging later in life, are often characterized by neuropsychiatric manifestations including psychosis. This study aimed to determine whether it would be useful to screen patients presenting with a psychotic disorder for IEMs by a single blood sample using Next Generation Sequencing (NGS), in order to detect rare, treatable causes of psychotic disorders. Blood was drawn from 60 patients with a psychotic disorder, with a duration of illness of less than 5 years. Read More

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Identification of 2,2-Dimethylbutanoic Acid (HST5040), a Clinical Development Candidate for the Treatment of Propionic Acidemia and Methylmalonic Acidemia.

J Med Chem 2021 Apr 13. Epub 2021 Apr 13.

HemoShear Therapeutics Inc., 501 Locust Avenue, Charlottesville, Virginia 22902, United States.

Propionic acidemia (PA) and methylmalonic acidemia (MMA) are rare autosomal recessive disorders of propionyl-CoA (P-CoA) catabolism, caused by a deficiency in the enzymes P-CoA carboxylase and methylmalonyl-CoA (M-CoA) mutase, respectively. PA and MMA are classified as intoxication-type inborn errors of metabolism because the intramitochondrial accumulation of P-CoA, M-CoA, and other metabolites results in secondary inhibition of multiple pathways of intermediary metabolism, leading to organ dysfunction and failure. Herein, we describe the structure-activity relationships of a series of short-chain carboxylic acids which reduce disease-related metabolites in PA and MMA primary hepatocyte disease models. Read More

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Biomarkers for liver disease in urea cycle disorders.

Mol Genet Metab 2021 Apr 8. Epub 2021 Apr 8.

Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA. Electronic address:

Background: Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. As therapies for hyperammonemia associated with urea cycle dysfunction have improved, chronic complications, such as liver disease, have become increasingly apparent in individuals with UCDs. Liver disease in UCDs may be associated with hepatic inflammation, hepatic fibrosis, portal hypertension, liver cancer and even liver failure. Read More

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A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance: a retrospective, single-center study and the generation of www.emergencyprotocol.net.

J Inherit Metab Dis 2021 Apr 12. Epub 2021 Apr 12.

Section of Metabolic Diseases, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.

Introduction: Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long-term data on outcomes using emergency letters are lacking.

Methods: This is a retrospective, observational, single-center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Read More

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Targeted urine metabolomics with a graphical reporting tool for rapid diagnosis of inborn errors of metabolism.

J Inherit Metab Dis 2021 Apr 11. Epub 2021 Apr 11.

Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.

The current diagnostic work-up of inborn errors of metabolism (IEM) is rapidly moving towards integrative analytical approaches. We aimed to develop an innovative, targeted urine metabolomics (TUM) screening procedure to accelerate the diagnosis of patients with IEM. Urinary samples, spiked with 3 stable isotope-labelled internal standards, were analysed for 258 diagnostic metabolites with an UHPLC-QTOF-MS configuration run in positive and negative ESI modes. Read More

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[Molybdenum cofactor deficiency caused by gene mutation: a case report].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Apr;23(4):416-419

Department of Neurology, Children's Hospital of Chongqing Medical University/National Clinical Research Center for Child Health and Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.

A boy attended the hospital at the age of 1 month due to left hand tremor for 1 week. A blood test showed a reduction in serum uric acid and a cranial MRI showed encephalomalacia, atrophy, and cystic changes. The boy had microcephalus, unusual facial features (long face, long forehead, protruded forehead, long philtrum, low nasal bridge, facial swelling, and thick lower lip), hypertonia of lower extremities, and severe global developmental delay. Read More

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Inborn errors of STAT1 immunity.

Curr Opin Immunol 2021 Apr 8;72:59-64. Epub 2021 Apr 8.

Department of Pediatrics, Hiroshima University, Graduate School of Biomedical and Health Sciences, Hiroshima, Japan. Electronic address:

Signal transducer and activator of transcription 1 (STAT1) is a latent cytoplasmic transcription factor that is activated by multiple stimuli, including type I, II, and III interferons and interleukin-27. Inborn errors of human STAT1 immunity underlie 4 distinct disorders: autosomal recessive (AR) complete STAT1 deficiency, AR partial STAT1 deficiency, autosomal dominant (AD) STAT1 deficiency, and AD STAT1 gain-of-function. Each disease presents distinct clinical manifestations, excluding the difference in two AR STAT1 deficiencies, which are mainly explained by severity. Read More

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Immune cytopenias as a continuum in inborn errors of immunity: An in-depth clinical and immunological exploration.

Immun Inflamm Dis 2021 Apr 10. Epub 2021 Apr 10.

Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Background: Immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN) are disorders characterized by immune-mediated destruction of hematopoietic cell lineages. A link between pediatric immune cytopenias and inborn errors of immunity (IEI) was established in particular in the combined and chronic forms.

Objective: Aim of this study is to provide clinical-immunological parameters to hematologists useful for a prompt identification of children with immune cytopenias deserving a deeper immunological and genetic evaluation. Read More

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[Hyperammonaemic encephalopathy in adults without liver diseases].

Ugeskr Laeger 2021 Mar;183(13)

Hyperammonaemic encephalopathy (HAE) in adults in the absence of acute or chronic liver disease is a severe condition caused by inborn errors of metabolism or acquired conditions like bariatric surgery, medications or malignancy as summarised in this review. Metabolic defects are most often caused by partial defects in the urea cycle enzymes demasked by stressors, whereas mechanisms underlying the acquired causes are complex and often multifactorial. Awareness of HAE and knowledge of the causes can help the clinician to deal appropriately with patients presenting with symptoms suggesting HAE and no signs of liver disease. Read More

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Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta.

Arterioscler Thromb Vasc Biol 2021 Apr 8:ATVBAHA120315587. Epub 2021 Apr 8.

UMR Inserm 1256 N-GERE (Nutrition, Génetique et Exposition aux Risques Environmentaux) (B.B., S.H., R.-M.G.-R., J.-L.G.).

Objective: Deficiency in vitamin B12/folate (methyl donor deficiency [MDD]) produces cardiovascular outcomes during aging and fetal programming effects in newborns of MDD mothers. Whether fetal programming provokes long-term effects on aorta remains largely unknown. Approach and Results: We investigated the impact of fetal programming on ascending aorta of aged rats born from mothers subjected to MDD during gestation/lactation. Read More

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A Novel TRAF3IP2 Mutation Causing Chronic Mucocutaneous Candidiasis.

J Clin Immunol 2021 Apr 7. Epub 2021 Apr 7.

Primary Immunodeficiencies Unit, Hospital Dona Estefânia-CHLC, EPE, Rua Jacinta Marto, 1169-045, Lisbon, Portugal.

Inborn errors of the IL-17-mediated signaling have been associated with chronic mucocutaneous candidiasis (CMC). We describe a patient with CMC, atopic dermatitis, enamel dysplasia, and recurrent parotitis harboring a novel compound heterozygous mutation of TRAF3IP2, leading to autosomal recessive ACT1 deficiency and deficient IL-17 signaling. Read More

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Familial hyperphosphatemic tumoral calcinosis in an unusual and usual sites and dramatic improvement with the treatment of acetazolamide, sevelamer and topical sodium thiosulfate.

J Pediatr Endocrinol Metab 2021 Apr 6. Epub 2021 Apr 6.

Department of Inborn Errors of Metabolism, Faculty of Medicine, Gazi University, Ankara, Turkey.

Objectives: Familial hyperphosphatemic tumoral calcinosis is a rare disorder characterized by hyperphosphatemia with recurrent ectopic periarticular calcifications, in addition to other visceral and vascular manifestations, without any inflammatory or neoplastic disorder. The available treatment strategies are limited. Here we report an eight year old female patient with recurrent lesions under the chin, and bilateral hips which are painful and improving of the size of the lesions and hyperphosphatemia. Read More

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Two patients from Turkey with a novel variant in the gene and review of the literature.

J Pediatr Endocrinol Metab 2021 Apr 6. Epub 2021 Apr 6.

Deparment of Pediatric Metabolism and Nutrition, Gazi University School of Medicine, Çankaya, Ankara, Turkey.

Objectives: GM2 gangliosidosis is a rare form of inborn errors of metabolism including Tay-Sachs disease, Sandhoff disease, and GM2 activator deficiency. GM2 activator protein deficiency is an ultra-rare form of GM2 gangliosidosis. To date, 16 cases of GM2 activator protein deficiency have been reported in the literature, and among them, 11 cases were the infantile form of the disease. Read More

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Plasma Phospholipidomic Profile Differs between Children with Phenylketonuria and Healthy Children.

J Proteome Res 2021 Apr 5. Epub 2021 Apr 5.

Mass Spectrometry Center, LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.

Phenylketonuria (PKU) is a disease of the catabolism of phenylalanine (Phe), caused by an impaired function of the enzyme phenylalanine hydroxylase. Therapeutics is based on the restriction of Phe intake, which mostly requires a modification of the diet. Dietary restrictions can lead to imbalances in specific nutrients, including lipids. Read More

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Current and Future Therapeutic Approaches for Thymic Stromal Cell Defects.

Front Immunol 2021 18;12:655354. Epub 2021 Mar 18.

Great Ormond Street Institute of Child Health, University College London, London, United Kingdom.

Inborn errors of thymic stromal cell development and function lead to impaired T-cell development resulting in a susceptibility to opportunistic infections and autoimmunity. In their most severe form, congenital athymia, these disorders are life-threatening if left untreated. Athymia is rare and is typically associated with complete DiGeorge syndrome, which has multiple genetic and environmental etiologies. Read More

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Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience.

Front Immunol 2021 19;12:630691. Epub 2021 Mar 19.

Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation. To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India. Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Read More

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Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients' Lives, and Reduce Costs.

Nanomaterials (Basel) 2021 Mar 16;11(3). Epub 2021 Mar 16.

Department of Biology and Biotechnology "C. Darwin", University of Rome Sapienza, 00185 Rome, Italy.

Vitamin B12 (VitB12) is a naturally occurring compound produced by microorganisms and an essential nutrient for humans. Several papers highlight the role of VitB12 deficiency in bone and heart health, depression, memory performance, fertility, embryo development, and cancer, while VitB12 treatment is crucial for survival in inborn errors of VitB12 metabolism. VitB12 is administrated through intramuscular injection, thus impacting the patients' lifestyle, although it is known that oral administration may meet the specific requirement even in the case of malabsorption. Read More

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Neonatal Urine Screening Program in the Province of Quebec: Technological Upgrade from Thin Layer Chromatography to Tandem Mass Spectrometry.

Int J Neonatal Screen 2021 Mar 20;7(1). Epub 2021 Mar 20.

Division of Medical Genetics, Department of Pediatrics, Centre de Recherche-CHUS, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.

The Quebec Neonatal Urine Screening Program was initiated in 1971 with overall screening inception of newborns in 1973. Forty-seven years later, over 3.5 million babies have been screened for up to 25 inborn errors of metabolism divided into two groups: (1) urea cycle disorders and organic acidurias; and (2) disorders of amino acid metabolism and transport. Read More

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β3-Adrenoreceptors as ROS Balancer in Hematopoietic Stem Cell Transplantation.

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Division of Pediatric Oncology/Hematology, Meyer University Children's Hospital, 50139 Florence, Italy.

In the last decades, the therapeutic potential of hematopoietic stem cell transplantation (HSCT) has acquired a primary role in the management of a broad spectrum of diseases including cancer, hematologic conditions, immune system dysregulations, and inborn errors of metabolism. The different types of HSCT, autologous and allogeneic, include risks of severe complications including acute and chronic graft-versus-host disease (GvHD) complications, hepatic veno-occlusive disease, lung injury, and infections. Despite being a dangerous procedure, it improved patient survival. Read More

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Opportunities and challenges for the computational interpretation of rare variation in clinically important genes.

Am J Hum Genet 2021 Apr;108(4):535-548

Departments of Bioengineering & Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address:

Genome sequencing is enabling precision medicine-tailoring treatment to the unique constellation of variants in an individual's genome. The impact of recurrent pathogenic variants is often understood, however there is a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequential variants and associated mechanisms. Read More

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Redox-Linked Coordination Chemistry Directs Vitamin B Trafficking.

Acc Chem Res 2021 Apr 2. Epub 2021 Apr 2.

Department of Biological Chemistry, Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.

ConspectusMetals are partners for an estimated one-third of the proteome and vary in complexity from mononuclear centers to organometallic cofactors. Vitamin B or cobalamin represents the epitome of this complexity and is the product of an assembly line comprising some 30 enzymes. Unable to biosynthesize cobalamin, mammals rely on dietary provision of this essential cofactor, which is needed by just two enzymes, one each in the cytoplasm (methionine synthase) and the mitochondrion (methylmalonyl-CoA mutase). Read More

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Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity.

Cell Mol Immunol 2021 Apr 1. Epub 2021 Apr 1.

Department of Rheumatology and Immunology, Hannover Medical School, Hanover, Germany.

In addition to susceptibility to infections, conventional primary immunodeficiency disorders (PIDs) and inborn errors of immunity (IEI) can cause immune dysregulation, manifesting as lymphoproliferative and/or autoimmune disease. Autoimmunity can be the prominent phenotype of PIDs and commonly includes cytopenias and rheumatological diseases, such as arthritis, systemic lupus erythematosus (SLE), and Sjogren's syndrome (SjS). Recent advances in understanding the genetic basis of systemic autoimmune diseases and PIDs suggest an at least partially shared genetic background and therefore common pathogenic mechanisms. Read More

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Neonatal-Onset Familial Mediterranean Fever in an Infant with Human Parainfluenza Virus-4 Infection.

Neonatology 2021 Mar 31:1-5. Epub 2021 Mar 31.

Maternal and Child Health Department, Padua University, Padua, Italy.

Unusual, severe infections or inflammatory episodes in newborns and infants are largely unexplained and often attributed to immature immune responses. Inborn errors of immunity (IEI) are increasingly recognized as the etiology of life-threatening inflammatory and infectious diseases in infancy. We describe a patient with a unique neonatal-onset Familial Mediterranean Fever (FMF) due to compound heterozygous variants in MEFV, presenting as pleuritis following human parainfluenza virus-4 infection. Read More

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Comprehensive Comparison between 222 CTLA-4 Haploinsufficiency and 212 LRBA Deficiency Patients: A Systematic Review.

Clin Exp Immunol 2021 Mar 31. Epub 2021 Mar 31.

Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

CTLA-4 haploinsufficiency (CHAI) and LRBA deficiency (LATAIE) are newly identified inborn errors of immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunologic, and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science, and Scopus databases and included studies were systematically evaluated. Read More

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Clinical and biochemical footprints of inherited metabolic disease. V. Cerebral palsy phenotypes.

Mol Genet Metab 2021 Mar 13. Epub 2021 Mar 13.

National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Cerebral palsy is the most common physical disability of childhood describing a heterogeneous group of neurodevelopmental disorders that cause activity limitation, but often are accompanied by disturbances of sensation, perception, cognition, communication and behavior, or by epilepsy. Inborn errors of metabolism have been reported in the literature as presenting with features of cerebral palsy. We reviewed and updated the list of metabolic disorders known to be associated with symptoms suggestive of cerebral palsy and found more than 150 relevant IEMs. Read More

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Autoimmune Manifestations among Patients with Monogenic Inborn Errors of Immunity.

Pediatr Allergy Immunol 2021 Mar 27. Epub 2021 Mar 27.

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran.

Background: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunological, and molecular data of monogenic IEI patients with and without autoimmune manifestations.

Methods: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. Read More

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Increasing the spectrum of white matter diseases with tigroid pattern on MRI: glutaric aciduria type 1 - case report.

BMC Pediatr 2021 Mar 27;21(1):146. Epub 2021 Mar 27.

Department of Inborn Errors of Metabolism and Paediatrics, Institute of Mother and Child, Warsaw, Poland.

Background: Most white matter diseases present on magnetic resonance imaging as focal or diffuse T2-hyperintensities. However, in a few of them, radially oriented stripes of low (relatively normal) signal intensity are observed within diffusely affected T2-hyperintense cerebral white matter and are called "tigroid pattern" in the literature. The fornix is a tiny white matter fibers bundle playing crucial role in cognitive functioning, easily overlooked on magnetic resonance imaging and not described in inborn errors of metabolism. Read More

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Rapid Detection and Treatment of Inborn Errors of Metabolism in the Newborn Period: Beginning of a New Trend.

Indian J Pediatr 2021 Mar 26. Epub 2021 Mar 26.

Institute of Medical Genetics & Genomics, Sir Ganga Ram Hospital, New Delhi, 110060, India.

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Inborn errors of immunity-recent advances in research on the pathogenesis.

Inflamm Regen 2021 Mar 25;41(1). Epub 2021 Mar 25.

Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.

Primary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Read More

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[Clinical and molecular genetic analysis of a case of MEGDEL syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Mar;38(3):271-274

Shanxi Rehabilitation Research Center, Taiyuan, Shanxi 030000, China.

Objective: To explore the clinical and genetic characteristics of a child with MEGDEL syndrome.

Methods: Clinical data of the child was reviewed. Peripheral blood samples of the child and his parents were collected. Read More

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