8,654 results match your criteria adults inborn


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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[Clinical features and gene mutations of 6 patients with carnitine palmitoyltransferase 1A deficiency].

Zhonghua Yi Xue Za Zhi 2021 Apr;101(14):1041-1044

Department of Pediatric Endocrinology and Genetic Metabolism, Shanghai Xinhua Children's Hospital, Shanghai Institute for Pediatric Research, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

The clinical and biochemical data and gene sequencing results of patients with carnitine palmitoyltransferase 1A deficiency were analyzed, in order to improve the understanding of the disease. Six patients (5 males and 1 female, aged from 1 to 8 years old) with carnitine palmitoyltransferase 1A deficiency from Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital between 2008 and 2019 were included. Two cases were detected by neonatal screening and had no clinical symptoms. Read More

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Parkinsonism and iron deposition in two adult patients with L-2-hydroxiglutaric aciduria.

Parkinsonism Relat Disord 2021 Apr 1;86:45-47. Epub 2021 Apr 1.

Neurology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal.

L-2-hydroxiglutaric aciduria (L2HGA) is a rare, childhood-onset, organic aciduria, with characteristic clinical (cerebellar ataxia) and neuroimaging (subcortical leukodystrophy) features. Movement disorders in this condition are usually of hyperkinetic type. Herein is reported the case of two adult siblings with recent L2HGA diagnosis, presenting with dopa-responsive parkinsonism and MRI iron deposition. Read More

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Cerebrotendinous xanthomatosis without neurological involvement.

J Intern Med 2021 Apr 8. Epub 2021 Apr 8.

Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.

Background: Cerebrotendinous xanthomatosis (CTX) is an autosomal recessively inherited inborn error of metabolism. Neurological symptoms are considered to be a clinical hallmark of untreated adult patients. We describe a 'milder CTX phenotype', without neurological involvement. 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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The Adult Phenylketonuria (PKU) Gut Microbiome.

Microorganisms 2021 Mar 4;9(3). Epub 2021 Mar 4.

Department of Microbiology, Immunology, and Genetics, Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

Phenylketonuria (PKU) is an inborn error of phenylalanine metabolism primarily treated through a phenylalanine-restrictive diet that is frequently supplemented with an amino acid formula to maintain proper nutrition. Little is known of the effects of these dietary interventions on the gut microbiome of PKU patients, particularly in adults. In this study, we sequenced the V4 region of the 16S rRNA gene from stool samples collected from adults with PKU ( = 11) and non-PKU controls ( = 21). Read More

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Alkaptonuria in Turkey: Clinical and molecular characteristics of 66 patients.

Eur J Med Genet 2021 Mar 18;64(5):104197. Epub 2021 Mar 18.

Department of Pediatric Metabolism and Nutrition, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey; Izmir Biomedicine and Genome Center, Izmir, Turkey. Electronic address:

Alkaptonuria (AKU) is an inborn error of metabolism caused by the deficiency of homogentisate 1,2-dioxygenase (HGD) as a result of a defect in the HGD gene. HGD enzyme deficiency results in accumulation of homogentisic acid (HGA) in the body, which in turn leads to multisystemic clinical symptoms. The present study aimed to investigate the presenting symptoms, age at diagnosis, and clinical and genetic characteristics of AKU patients followed-up in different centers in Turkey. Read More

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How to detect late-onset inborn errors of metabolism in patients with movement disorders - A modern diagnostic approach.

Parkinsonism Relat Disord 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands; Expertise Center Movement Disorders Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, the Netherlands. Electronic address:

We propose a modern approach to assist clinicians to recognize and diagnose inborn errors of metabolism (IEMs) in adolescents and adults that present with a movement disorder. IEMs presenting in adults are still largely unexplored. These disorders receive little attention in neurological training and daily practice, and are considered complicated by many neurologists. Read More

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Gene delivery using AAV8 for disease stabilization in a bimodal gene therapy approach for the treatment of ADA-deficient SCID.

Mol Ther Methods Clin Dev 2021 Mar 15;20:765-778. Epub 2021 Feb 15.

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Adenosine deaminase (ADA) deficiency is an inborn error of metabolism affecting multiple systems and causing severe combined immunodeficiency. We tested intravenous administration of recombinant adeno-associated virus (AAV) 2/8-ADA vector in ADA-deficient neonate and adult mice or as part of a bimodal approach comprised of rAAV treatment at birth followed by infusion of lentiviral vector (LV)-modified lineage-depleted bone marrow cells at 8 weeks. ADA mice treated with rAAV and enzyme replacement therapy (ERT) for 30 days were rescued from the lethal pulmonary insufficiency, surviving out to 180 days without further treatment. Read More

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Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency.

J Med Genet 2021 Mar 18. Epub 2021 Mar 18.

Normandie Univ, UNIROUEN, CHU Rouen, INSERM U1245, 76000 Rouen, Normandy Center for Genomic and Personalized Medicine, Rouen, France

Introduction: This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB).

Methods: Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed.

Results: The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Read More

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Hand fine motor control in classic galactosemia.

J Inherit Metab Dis 2021 Mar 15. Epub 2021 Mar 15.

Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.

Classic galactosemia (CG) is a rare inborn error of metabolism that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection and rapid and lifelong dietary restriction of galactose, which is the current standard of care, most patients grow to experience a broad range of complications that can include motor difficulties. The goal of this study was to characterize hand fine motor control deficit among children and adults with classic galactosemia (CG). Read More

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Pulmonary Alveolar Microlithiasis Complicated by Tuberculosis.

N Engl J Med 2021 03;384(10):e36

Katutura State Hospital, Windhoek, Namibia

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Nutrition in Chronic Liver Disease: Consensus Statement of the Indian National Association for Study of the Liver.

J Clin Exp Hepatol 2021 Jan-Feb;11(1):97-143. Epub 2020 Oct 1.

Institute of Liver & Digestive Diseases, BL Kapur Memorial Hospital, New Delhi, 110005, India.

Malnutrition and sarcopenia are common in patients with chronic liver disease and are associated with increased risk of decompensation, infections, wait-list mortality and poorer outcomes after liver transplantation. Assessment of nutritional status and management of malnutrition are therefore essential to improve outcomes in patients with chronic liver disease. This consensus statement of the Indian National Association for Study of the Liver provides a comprehensive review of nutrition in chronic liver disease and gives recommendations for nutritional screening and treatment in specific clinical scenarios of malnutrition in cirrhosis in adults as well as children with chronic liver disease and metabolic disorders. Read More

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October 2020

Extreme phenotypes approach to investigate host genetics and COVID-19 outcomes.

Genet Mol Biol 2021 1;44(1 Suppl 1):e20200302. Epub 2021 Mar 1.

Universidade de São Paulo, Instituto de Biociências, Departamento de Genética e Biologia Evolutiva, Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, São Paulo, SP, Brazil.

COVID-19 comprises clinical outcomes of SARS-CoV-2 infection and is highly heterogeneous, ranging from asymptomatic individuals to deceased young adults without comorbidities. There is growing evidence that host genetics play an important role in COVID-19 severity, including inborn errors of immunity, age-related inflammation and immunosenescence. Here we present a brief review on the known order of events from infection to severe system-wide disturbance due to COVID-19 and summarize potential candidate genes and pathways. Read More

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A randomized trial to examine the impact of food on pharmacokinetics of 4-phenylbutyrate and change in amino acid availability after a single oral administration of sodium 4-phenylbutyrarte in healthy volunteers.

Mol Genet Metab 2021 Apr 23;132(4):220-226. Epub 2021 Feb 23.

Laboratory of Molecular Pharmacokinetics, Graduate School of Pharmaceutical Science, The University of Tokyo, Japan. Electronic address:

Urea cycle disorders (UCDs), inborn errors of hepatocyte metabolism, result in the systemic accumulation of ammonia to toxic levels. Sodium 4-phenylbutyrate (NaPB), a standard therapy for UCDs for over 20 years, generates an alternative pathway of nitrogen deposition through glutamine consumption. Administration during or immediately after a meal is the accepted use of NaPB. Read More

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Current and Emerging Clinical Treatment in Mitochondrial Disease.

Mol Diagn Ther 2021 03 1;25(2):181-206. Epub 2021 Mar 1.

Wellcome Centre for Mitochondrial Research, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.

Primary mitochondrial disease (PMD) is a group of complex genetic disorders that arise due to pathogenic variants in nuclear or mitochondrial genomes. Although PMD is one of the most prevalent inborn errors of metabolism, it often exhibits marked phenotypic variation and can therefore be difficult to recognise. Current treatment for PMD revolves around supportive and preventive approaches, with few disease-specific therapies available. Read More

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Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.

Mol Genet Metab 2021 Apr 20;132(4):234-243. Epub 2021 Feb 20.

Lysosomal Storage Disorders Unit, Royal Free Hospital NHS Foundation Trust and University College London, London, UK. Electronic address:

Background: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD. Read More

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Hepatobiliary phenotypes of adults with alpha-1 antitrypsin deficiency.

Gut 2021 Feb 25. Epub 2021 Feb 25.

Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE LIVER), Aachen, Germany

Objective: Alpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the 'Pi*Z' variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous 'Pi*Z' carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common 'Pi*S' variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD. Read More

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February 2021

Systemic autoinflammatory disease in adults.

Autoimmun Rev 2021 Apr 17;20(4):102774. Epub 2021 Feb 17.

Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium; KU Leuven, Department of Microbiology, Immunology, and Transplantation, Laboratory of Clinical Infectious and Inflammatory Disorders, Leuven, Belgium.

Systemic autoinflammatory disorders comprise an expanding group of rare conditions. They are mediated by dysfunction of the innate immune system and share a core of phenotypic manifestations including recurrent attacks of fever, cutaneous signs, chest or abdominal pain, lymphadenopathy, vasculopathy, and musculoskeletal symptoms. Diagnosis is often established in childhood, but a growing number of adult patients are being recognized with systemic autoinflammatory disorders, including adult-onset disease. Read More

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The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update by the IUIS Committee.

J Clin Immunol 2021 Apr 18;41(3):666-679. Epub 2021 Feb 18.

Department of Immunology and Microbiology, Laboratory for Inborn Errors of Immunity, Department of Pediatrics, University Hospitals Leuven and KU Leuven, 3000, Leuven, Belgium.

The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inborn errors of immunity. As the next formal report from the IUIS Expert Committee will not be published until 2022, we felt it important to provide the community with a brief update of recent contributions to the field of inborn errors of immunity. Read More

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Givosiran to treat acute porphyria.

Drugs Today (Barc) 2021 Jan;57(1):47-59

Section on Gastroenterology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina, USA.

Porphyrias are a family of rare diseases chiefly due to inborn errors of heme biosynthesis. The porphyrias are generally characterized either by the main site of overproduction of heme precursors (hepatic or erythropoietic) or the main clinical manifestations (acute or cutaneous). The regulation of 5- (or δ)-aminolevulinic acid synthase 1 (ALAS1) plays a key role in the pathway of normal hepatic heme synthesis, providing insight into the pathophysiologic mechanisms and potential therapeutic targets for the treatment of the porphyrias. Read More

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January 2021

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

Front Genet 2020 15;11:598760. Epub 2021 Jan 15.

Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

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. Read More

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January 2021

Epidermal T cell subsets-Effect of age and antigen exposure in humans and mice.

Contact Dermatitis 2021 Feb 11. Epub 2021 Feb 11.

The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Background: Epidermal T cells play a central role in immune surveillance and in inflammatory skin diseases. Major differences in the epidermal T cell composition are found between adult humans and antigen-inexperienced laboratory mice. Whether this is due to inborn species differences, to different environmental exposures, or a combination of the two is a matter of debate. Read More

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February 2021

Continuation of pegvaliase treatment during pregnancy: A case report.

Mol Genet Metab Rep 2021 Mar 27;26:100713. Epub 2021 Jan 27.

Division of Metabolic Disorders, CHOC Children's Hospital, Orange, CA, United States of America.

Phenylalanine hydroxylase (PAH) deficiency is an inborn error of phenylalanine (Phe) metabolism that results in the buildup of dietary Phe to potentially toxic levels. Poorly controlled Phe levels in women of childbearing age are particularly worrisome due to the toxic effect of elevated Phe on fetal development. Pegvaliase was recently approved as an enzyme substitution therapy to reduce Phe concentrations in adult patients with PAH deficiency who have suboptimal Phe control on existing management. Read More

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Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine.

J Exp Med 2021 04;218(4)

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.

Yellow fever virus (YFV) live attenuated vaccine can, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete IFNAR1 deficiency was reported in one 12-yr-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 yr with unexplained life-threatening YFV vaccine-associated disease. Read More

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Minor Clinical Impact of COVID-19 Pandemic on Patients With Primary Immunodeficiency in Israel.

Front Immunol 2020;11:614086. Epub 2021 Jan 14.

The Jeffrey Modell Foundation Israeli Network for Primary Immunodeficiency, New York, NY, United States.

In the last few months the world has witnessed a global pandemic due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19). Obviously, this pandemic affected individuals differently, with a significant impact on populations considered to be at high-risk. One such population, was assumed to be patients with primary genetic defect involving components or pathways of the immune system. Read More

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February 2021

Distinct antibody repertoires against endemic human coronaviruses in children and adults.

JCI Insight 2021 02 22;6(4). Epub 2021 Feb 22.

Research Branch, Sidra Medicine, Doha, Qatar.

Four endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these "common cold" viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage immunoprecipitation sequencing. Read More

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February 2021

[The metabolic newborn screening as a healthcare model of the precision medicine. Perspective from the Spanish Association for the Study of Congenital Errors of Metabolism (AECOM).]

Rev Esp Salud Publica 2021 Jan 26;95. Epub 2021 Jan 26.

Medicina Interna. Consulta de Enfermedades minoritarias y Enfermedades Metabólicas Congénitas del Adulto. Hospital Universitario 12 de Octubre (CSUR-MetabERN). Instituto de Investigación Hospital 12 de Octubre (i+12), CIBERER. Universidad Complutense de Madrid. España.

Newborn screening programs for congenital diseases aim to achieve a presymptomatic and early diagnosis of treatable disorders, in order to prevent or significantly reduce morbidity and/or mortality. Many of the conditions included in these programs are inborn errors of metabolism (IEM); however, the detection of endocrine, hematological, immunological, cardiovascular diseases, and congenital hearing loss are also included in many of them. Newborn screening tests are not diagnostic and therefore additional tests are needed to confirm or exclude the suspected diagnosis. Read More

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January 2021

Neuronal ceroid lipofuscinosis: genetic and phenotypic spectrum of 14 patients from Turkey.

Neurol Sci 2021 Mar 23;42(3):1103-1111. Epub 2021 Jan 23.

Clinical Chemistry Department, Ege University Faculty of Medicine, İzmir, Turkey.

Introduction And Purpose: Neuronal ceroid lipofuscinoses (NCLs) is a group of congenital metabolic diseases where the neurodegenerative process with the accumulation of ceroid and lipofuscin autofluorescent storage materials is at the forefront. According to the age of presentation, NCLs are classified as congenital, infantile (INCL), late infantile (LINCL), juvenile (JNCL), and adult (ANCL) NCLs. In our study, it was aimed to discuss the clinical and molecular characteristics of our patients diagnosed with NCL. Read More

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