3,268 results match your criteria inborn error


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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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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Genotypic and phenotypic features in Turkish patients with classic nonketotic hyperglycinemia.

Metab Brain Dis 2021 Apr 1. Epub 2021 Apr 1.

Metabolism Unit, Sami Ulus Children Hospital, Babur cad. No: 44, Altındağ, Ankara, 06080, Turkey.

Nonketotic hyperglycinemia is an autosomal recessive inborn error of glycine metabolism, characterized by deficient activity of the glycine cleavage enzyme system. Classic nonketotic hyperglycinemia is caused by mutations or genomic changes in genes that encode the protein components of the glycine cleavage enzyme system. We aimed to investigate clinical, biochemical, radiological findings and molecular genetic data in ten Turkish patients with classic nonketotic hyperglycinemia. Read More

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CRISPR/Cas9 generated knockout mice lacking phenylalanine hydroxylase protein as a novel preclinical model for human phenylketonuria.

Sci Rep 2021 Mar 31;11(1):7254. Epub 2021 Mar 31.

Genomic Medicine Unit, Sanofi, 49 New York Avenue, Framingham, MA, 01701, USA.

Phenylketonuria (PKU) is an autosomal recessive inborn error of L-phenylalanine (Phe) metabolism. It is caused by a partial or complete deficiency of the enzyme phenylalanine hydroxylase (PAH), which is necessary for conversion of Phe to tyrosine (Tyr). This metabolic error results in buildup of Phe and reduction of Tyr concentration in blood and in the brain, leading to neurological disease and intellectual deficits. Read More

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Inherited Metabolic Causes of Stroke in Children: Mechanisms, Types, and Management.

Front Neurol 2021 4;12:633119. Epub 2021 Mar 4.

Department of Genetics and Precision Medicine (GPM), King Abdullah Specialized Children's Hospital, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.

A stroke should be considered in cases of neurologic decompensation associated with inherited metabolic disorders. A resultant stroke could be a classical ischemic stroke (vascular stroke) or more commonly a "metabolic stroke." A metabolic stroke begins with metabolic dysfunctions, usually caused by a stressor, and leads to the rapid onset of prolonged central neurological deficits in the absence of vessel occlusion or rupture. 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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Difficulties in the dietary management of a girl with two diseases requiring a special diet.

J Mother Child 2021 Jan 29;22(3):225-228. Epub 2021 Jan 29.

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

3-Methylcrotonylglycinuria (3-MCG) is an autosomal recessive inborn error of leucine metabolism caused by the deficiency of 3-methylocrotonyl-CoA carboxylase (3-MCC deficiency). It is the most commonly detected organic aciduria in newborn screening conducted by tandem mass spectrometry (MS/MS) [1, 2]. The clinical phenotype is heterogeneous, ranging from asymptomatic to acute metabolic decompensations [3, 4]. Read More

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January 2021

Deficyt aktywności transaldolazy - Obraz kliniczny, patogeneza, diagnostyka.

J Mother Child 2021 Jan 29;22(2):187-196. Epub 2021 Jan 29.

Klinika Pediatrii, Żywienia i Chorób Metabolicznych, Instytut ,,Pomnik-Centrum Zdrowia Dziecka'', Warszawa, Polska.

Deficyt aktywności transaldolazy należy do wrodzonych błędów metabolizmu na szlaku przemiany pentoz, który do tej pory rozpoznano i opisano u 33 pacjentów, w tym 4 z Polski.W artykule przedstawiono obraz kliniczny, patogenezę i diagnostykę choroby. Autorzy przedstawili ponadto własną propozycję algorytmu diagnostyki deficytu transaldolazy. Read More

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January 2021

Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism.

Commun Biol 2021 Mar 19;4(1):367. Epub 2021 Mar 19.

Radboud University, Institute for Molecules and Materials, FELIX Laboratory, Toernooiveld 7, Nijmegen, the Netherlands.

The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding their pathophysiology. A primary metabolite that accumulates in the inborn error phenylketonuria is phenylalanine, however its levels do not always directly correlate with clinical outcomes. Here we combine infrared ion spectroscopy and NMR spectroscopy to identify the Phe-glucose Amadori rearrangement product as a biomarker for phenylketonuria. 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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Validation of plasma amino acid profile using UHPLC-mass spectrometer (QDa) as a screening method in a metabolic disorders reference centre: Performance and accreditation concerns.

Clin Biochem 2021 Mar 15. Epub 2021 Mar 15.

Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Tours, Tours, France; Unité INSERM U1253, équipe "neurogénomique et physiopathologie neuronale", Université de Tours, Tours, France; Centre de référence des maladies héréditaires de métabolisme - filière G2M, France.

Introduction: Amino acid (AA) analysis in plasma is essential for diagnosis and monitoring of inborn errors of metabolism (IEM). The efficacy of patient management is governed by the rapidity of AA profile availability, along with the robustness of the method. French quality guidelines and progress made in analytical techniques have led biologists to develop AA profile exploration via mass spectrometry (MS). Read More

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Arginine to ornithine ratio as a diagnostic marker in patients with positive newborn screening for hyperargininemia.

Mol Genet Metab Rep 2021 Jun 3;27:100735. Epub 2021 Mar 3.

Biochemical Genetics, Advanced Diagnostics-Genetics, Genomics and R&D, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92675, United States of America.

Arginase deficiency is a rare inborn error of metabolism that interrupts the final step of the urea cycle. Untreated individuals often present with episodic hyperammonemia, developmental delay, cognitive impairment, and spasticity in early childhood. The newborn screening (NBS) algorithms for arginase deficiency vary between individual states in the US but often include hyperargininemia and elevated arginine to ornithine (Arg/Orn) ratio. 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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Clinical Profile of Hyper-IgE Syndrome in India.

Front Immunol 2021 26;12:626593. Epub 2021 Feb 26.

Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility to skin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES. Read More

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February 2021

Human MALT1 deficiency and predisposition to infections.

Curr Opin Immunol 2021 Mar 11;72:1-12. Epub 2021 Mar 11.

Department of Pediatrics, British Columbia Children's Hospital, The University of British Columbia, Vancouver, BC, Canada. Electronic address:

Human germline MALT1 deficiency is an inborn error of immunity characterized by recurrent bacterial, viral, and fungal infections, periodontal disease, enteropathy, dermatitis, and failure to thrive. The number of identified MALT1-deficient patients have greatly increased in the past two years, which has significantly improved our understanding of the clinical features of this disorder. Patients frequently experience infections affecting the respiratory, skin, gastrointestinal, and blood systems. Read More

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Assessment of the effects of repeated freeze thawing and extended bench top processing of plasma samples using untargeted metabolomics.

Metabolomics 2021 03 11;17(3):31. Epub 2021 Mar 11.

Metabolon, 617 Davis Drive, Suite 100, Morrisville, NC, 27560, USA.

Introduction: Clinical metabolomics has utility as a screen for inborn errors of metabolism (IEM) and variant classification in patients with rare disease. It is important to understand and characterize preanalytical factors that influence assay performance during patient sample testing.

Objectives: To evaluate the impact of extended thawing of human EDTA plasma samples on ice prior to extraction as well as repeated freeze-thaw cycling of samples to identify compounds that are unstable prior to metabolomic analysis. Read More

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Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type.

Orphanet J Rare Dis 2021 Mar 10;16(1):125. Epub 2021 Mar 10.

Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China.

Background: Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center.

Methods: 248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Read More

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Management of COVID-19 infection in organic acidemias.

Am J Med Genet A 2021 Mar 8. Epub 2021 Mar 8.

Division of Genetic, Genomic, and Metabolic Disorders, Children's Hospital of Michigan, Detroit, Michigan, USA.

The COVID-19 pandemic has affected the health and healthcare of individuals of all ages worldwide. There have been multiple reports and reviews documenting a milder effect and decreased morbidity and mortality in the pediatric population, but there have only been a small number of reports discussing the SARS-CoV-2 infection in the setting of an inborn error of metabolism (IEM). Here, we report two patients with underlying metabolic disorders, propionic acidemia and glutaric aciduria type 1, and discuss their clinical presentation, as well as their infectious and metabolic management. Read More

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Long-term outcome of a patient with Transcobalamin deficiency caused by the homozygous c.1115_1116delCA mutation in TCN2 gene: a case report.

Ital J Pediatr 2021 Mar 8;47(1):54. Epub 2021 Mar 8.

Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.

Background: Transcobalamin deficiency is a rare autosomal recessive inborn error of cobalamin transport (prevalence: < 1/1000000) which clinically manifests in early infancy.

Case Presentation: We describe the case of a 31 years old woman who at the age of 30 days presented with the classical clinical and laboratory signs of an inborn error of vitamin B metabolism. Family history revealed a sister who died at the age of 3 months with a similar clinical syndrome and with pancytopenia. Read More

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Life-Threatening Influenza, Hemophagocytic Lymphohistiocytosis and Probable Vaccine-Strain Varicella in a Novel Case of Homozygous Deficiency.

Front Immunol 2020 18;11:624415. Epub 2021 Feb 18.

Immunity and Inflammation Theme, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom.

STAT2 is a transcription factor that plays an essential role in antiviral immunity by mediating the activity of type I and III interferons (IFN-I and IFN-III). It also has a recently established function in the negative regulation of IFN-I signaling. Homozygous STAT2 deficiency is an ultra-rare inborn error of immunity which provides unique insight into the pathologic consequence of STAT2 dysfunction. Read More

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February 2021

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

Novel Mutation in the IDS Gene in Hunter Syndrome Associated with Severe Cardiac Lesions.

Clin Chem 2021 Mar;67(3):564-566

Department of Chemical Pathology and National Health Laboratory Service, Tshwane Academic Division, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.

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Treatment efficacy of high-dose creatine supplementation in a child with creatine transporter (SLC6A8) deficiency.

Mol Genet Genomic Med 2021 Mar 3:e1640. Epub 2021 Mar 3.

Department of Neurology, Guangzhou Women and Children's Medical Center, Guangzhou, China.

Background: Creatine transporter deficiency is an inborn error of metabolism caused by a deficiency in the creatine transporter protein encoded by the SLC6A8 gene. Previous treatment with creatine supplementation, either alone or in combination with creatine precursors (arginine or glycine), has been attempted; the efficacy of therapy, however, remains controversial.

Methods And Results: To analyze the treatment efficacy of high-dose creatine supplementation on creatine transporter deficiency, we reported a child diagnosed with creatine transporter deficiency, who was treated with a conventional dose of creatine (400 mg/kg/d) for 1 month, then twice the dose (800 mg/kg/d) for 2 months, and finally 3 times the dose (1200 mg/kg/d) for 3 months. Read More

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Multiple Sulfatase Deficiency (MSD): Review of the Literature and Case Reports of Two Siblings with Dental Caries and Trauma.

Case Rep Pediatr 2021 16;2021:6611548. Epub 2021 Feb 16.

Great Ormond Street Hospital, London, UK.

Multiple sulfatase deficiency (MSD) (MIM # 272200) is an extraordinarily rare inborn error of metabolism (IEM). The phenotypic spectrum is largely heterogeneous and attributed to the combined effects of deficiencies in the nine sulfatases currently known to be related to human diseases. Systemic sequelae of MSD are vast and multisystemic, primarily encompassing developmental delay and neurological, cardiopulmonary, dermatological, gastroenterological, and skeletal manifestations. Read More

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February 2021

Ethylmalonic encephalopathy ETHE1 p. D165H mutation alters the mitochondrial function in human skeletal muscle proteome.

Mitochondrion 2021 Feb 24;58:64-71. Epub 2021 Feb 24.

Institute of Bioinformatics, International Tech Park, Bangalore, India; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Manipal Academy of Higher Education, Manipal, India. Electronic address:

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. To study the molecular effects of ETHE1 p. D165H mutation, we employed mass spectrometry-based mitochondrial proteome and phosphoproteome profiling in the human skeletal muscle. Read More

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February 2021

[Autoimmune encephalitis-limbic encephalitis. A clinical case].

Rev Alerg Mex 2020 Jul-Sep;67(3):297-304

Hospital Infantil Universitario de San José, Bogotá, Colombia.

Background: Autoimmune encephalitis occurs as a subacute condition with a strong infectious association in children. In the last 20 years, the frequency of non-infectious cases has increased significantly.

Case Report: A previously healthy eight-year-old male child with normal neurodevelopment, without a history of consanguinity, manifested progressive neurological deterioration with autoimmune encephalitis-limbic encephalitis up to hypothalamic dysfunction. Read More

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February 2021

Recurrent abdominal pain, vomiting, velvet-like changes in the small intestine in a patient with multiple acyl-CoA dehydrogenase deficiency: a case report.

Transl Pediatr 2021 Jan;10(1):183-187

Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China.

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inborn error of metabolism in fatty acid oxidation. We described an unusual case of recurrent vomiting and abdominal pain in a child with MADD, presenting with velvet-like changes in the small intestine. Because of prominent gastrointestinal manifestations and small intestine ulcers, the patient was first diagnosed as Crohn's disease. Read More

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January 2021

[Disseminated infection caused by the bacillus Calmette-Guérin vaccine and SARS-CoV-2 coinfection in a patient with IL-12 receptor β1 subunit deficiency].

Rev Alerg Mex 2020 Oct-Dec;67(4):401-407

Instituto Mexicano del Seguro Social, Centro Médico Nacional La Raza, Hospital de Especialidades, Ciudad de México, México.

Background: Inborn errors of immunity manifest with a greater susceptibility to infections, autoimmunity, autoinflammatory diseases, allergies, or malignancies. One of these is the mendelian susceptibility to mycobacterial disease. The most frequent etiology is the complete autosomal recessive deficiency of the β1 subunit of the interleukin 12 receptor. Read More

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[Clinical and molecular inflammatory alterations in chronic granulomatous disease].

Rev Alerg Mex 2020 Oct-Dec;67(4):370-380

Secretaría de Salud, Instituto Nacional de Pediatría, Unidad de Investigación en Inmunodeficiencias, Ciudad de México, México.

Chronic granulomatous disease (CGD) is an inborn error of immunity. CGD is characterized by a deficiency in the function of the NADPH oxidase complex. CGD has been an opportunity to study the function of reactive oxygen species (ROS) in the innate immune system. Read More

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February 2021