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    12385 results match your criteria Pediatrics Inborn Errors of Metabolism

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    Actual Insights into Treatable Inborn Errors of Metabolism Causing Epilepsy.
    J Pediatr Neurosci 2018 Jan-Mar;13(1):13-23
    Department of Pediatrics, Child Neurology and Psychiatry-Division of Pediatric Neurology-Sapienza University of Rome, Rome, Italy.
    This review offers an update on a group of inborn errors of metabolism causing severe epilepsy with the onset in pediatric age (but also other neurological manifestations such as developmental delay or movement disorders) with available effective or potentially effective treatments. The main pathogenic and clinical features and general recommendations for the diagnostic and therapeutic workup of the following disorders are discussed: vitamin B-dependent epilepsies, cerebral folate deficiency, congenital disorders of serine metabolism, biotinidase deficiency, inborn errors of creatine metabolism, molybdenum cofactor deficiency, and glucose transporter 1 deficiency. Available treatments are more effective on epileptic manifestations (with the possibility of complete seizure control) and motor symptoms, whereas the benefits on cognitive outcome are usually minor. Read More

    The first pilot study of expanded newborn screening for inborn errors of metabolism and survey of related knowledge and opinions of health care professionals in Hong Kong.
    Hong Kong Med J 2018 Jun 4. Epub 2018 Jun 4.
    Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong.
    Introduction: Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. Read More

    Differential response to renal replacement therapy in neonatal-onset inborn errors of metabolism.
    Nephrology (Carlton) 2018 Jun 10. Epub 2018 Jun 10.
    Department of Pediatrics, Città della Salute e della Scienza, Regina Margherita Children's Hospital, Torino, Italy.
    Severe urea cycle defects (UCDs), organic acidemias (OAs), and maple syrup urine disease (MSUD) are life-threatening disorders presenting in the first days of life. Renal replacement therapy (RRT) is an emergency option in affected newborns, mostly performed as ultima ratio. We report our 10-year experience using emergency RRT in newborns with UCDs, OAs, and MSUD. Read More

    A proposed nosology of inborn errors of metabolism.
    Genet Med 2018 Jun 8. Epub 2018 Jun 8.
    Dietmar-Hopp Metabolic Center, University Children's Hospital, Heidelberg, Germany.
    Purpose: We propose a nosology for inborn errors of metabolism that builds on their recent redefinition.

    Methods: We established a strict definition of criteria to develop a self-consistent schema for inclusion of a disorder into the nosology.

    Results: We identified 1015 well-characterized inborn errors of metabolism described in the literature. Read More

    Metabolic etiologies in West syndrome.
    Epilepsia Open 2018 Jun 14;3(2):134-166. Epub 2018 Mar 14.
    Laboratory of Developmental Epilepsy Saul R. Korey Department of Neurology Montefiore/Einstein Epilepsy Center Albert Einstein College of Medicine Bronx New York U.S.A.
    West syndrome (WS) is an early life epileptic encephalopathy associated with infantile spasms, interictal electroencephalography (EEG) abnormalities including high amplitude, disorganized background with multifocal epileptic spikes (hypsarrhythmia), and often neurodevelopmental impairments. Approximately 64% of the patients have structural, metabolic, genetic, or infectious etiologies and, in the rest, the etiology is unknown. Here we review the contribution of etiologies due to various metabolic disorders in the pathology of WS. Read More

    Macrophage activation syndrome associated with griscelli syndrome type 2: case report and review of literature.
    Pan Afr Med J 2018 25;29:75. Epub 2018 Jan 25.
    Center for Hematology and Oncology Paediatrics, Children's hospital, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco.
    Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. Read More

    Treatable massive pericardial effusion and hypertrophic cardiomyopathy in an infant with a novel homozygous ACADVL mutation: A case report.
    Medicine (Baltimore) 2018 May;97(20):e10813
    Department of Pediatrics, College of Medicine, Pusan National University Children's Hospital, Yangsan.
    Rationale: Infantile-onset hypertrophic cardiomyopathy (HCMP) should be considered a largely genetic condition, although its onset is most often triggered by infection. Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare autosomal recessive inborn error of mitochondrial fatty acid β-oxidation that often causes severe cardiomyopathy and/or sudden death during the neonatal period.

    Patient Concerns: Herein, we report an infant with VLCAD deficiency who presented with severe cardiac manifestations, including massive pericardial effusion and HCMP. Read More

    A case report of neurological complications owing to lately diagnosed hyperargininemia emphasizing the role of national neonatal screening policies in the kingdom of Bahrain.
    Medicine (Baltimore) 2018 May;97(20):e10780
    Department of Internal Medicine, King Hamad University Hospital, Al Sayh, Bahrain.
    Introduction: Arginine is an essential amino acid that plays an important role in various body functions including cell division, wound healing, removal of ammonia, immune function, and release of hormones. Hyperargininemia, an autosomal recessive genetic disorder, is considered one of the least common urea cycle disorders. It rarely presents in the neonatal period but rather appears in children at the age between 2 and 4 years. Read More

    Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes.
    N Engl J Med 2018 05;378(20):1908-1919
    From the Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, Rome (F.D.B.), Clinica Pediatrica e Reumatologia, Unità Operativa Semplice Dipartimentale di Malattie Autoinfiammatorie e Immunodeficienze, IRCCS, Istituto G. Gaslini, Genoa (M.G.), the Pediatric Clinic, University of Brescia and Spedali Civili, Brescia (M.C.), and the Amyloidosis Research and Treatment Center, Biotechnology Research Laboratories, Fondazione IRCCS Policlinico San Matteo, Pavia (L.O.) - all in Italy; the Division of Pediatric Rheumatology, Hospital Sant Joan de Déu, Universitat de Barcelona (J.A.), and the Internal Medicine Department, Autoimmune and Systemic Diseases Unit, Hospital Vall d'Hebron (S.B.-R.), Barcelona, and the Pediatric Rheumatology Unit, Hospital Universitario y Politécnico La Fe, Valencia (I.C.P.) - all in Spain; the Rheumatology Unit, Hadassah-Hebrew University Hospital (E.B.-C.), and the Pediatric Rheumatology Unit, Shaare Zedek Medical Center (P.J.H.), Jerusalem, and Heller Institute of Medical Research and Medicine Faculty, Sheba Medical Center, Tel-Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (A.L.) - all in Israel; the Division of Pediatrics, University Medical Center Utrecht, Utrecht (J.F.), and the Radboud Expertise Center for Immunodeficiency and Autoinflammation, Department of Internal Medicine, Radboud University Medical Center, Nijmegen (A. Simon) - both in the Netherlands; the Departments of Pediatrics and Medicine, University of California at San Diego and Rady Children's Hospital San Diego, San Diego (H.M.H.); the Department of Pediatric Rheumatology, Centre de Référence des Maladies Auto-inflammatoires et de l'Amylose Inflammatoire, Centre Hospitalier Universitaire (CHU) de Bicêtre, Assistance Publique-Hopitaux de Paris (APHP), Université de Paris Sud (I.K.-P.), and Paris-Descartes University, Imagine Institute, Unité d'Immuno-Hématologie et Rhumatologie Pédiatrique, Hôpital Necker-Enfants Malades, APHP (P.Q.), Paris; the National Amyloidosis Centre, University College London Division of Medicine, Royal Free Campus (H.J.L.), and University College London, Great Ormond Street Institute of Child Health, and Great Ormond Street Hospital for Children NHS Foundation Trust (P.B.), London; the Department of Pediatrics, Hacettepe University, Ankara (S.O.), and the Department of Pediatric Rheumatology, Cerrahpasa Medical School (O.K.), and Istanbul Faculty of Medicine, Department of Internal Medicine, Division of Rheumatology (A.G.), Istanbul University, Istanbul - all in Turkey; the Department of Pediatrics, Division of Pediatric Rheumatology, Cleveland Clinic, Cleveland (A.Z.); the Department of Infectious Diseases and General Internal Medicine, CHU Sart-Tilman, University of Liège, Liege (M.M.), and the Department of Infectious Diseases and Immunity, Jessa Hospital, University of Hasselt, Hasselt (J.V.H.) - both in Belgium; the Department of Clinical Immunology, Center for Pediatric Hematology, Oncology, and Immunology, Moscow (A. Shcherbina); Pediatric Rheumatology of Western Switzerland, University of Lausanne, Lausanne, (M.H.), and Novartis, Basel (K.L., A. Speziale, G.J.) - both in Switzerland; the Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan (R.H.); and the Department of Pediatrics, Semmelweis Egyetem, Budapest, Hungary (T.C.).
    Background: Familial Mediterranean fever, mevalonate kinase deficiency (also known as the hyperimmunoglobulinemia D syndrome), and the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) are monogenic autoinflammatory diseases characterized by recurrent fever flares.

    Methods: We randomly assigned patients with genetically confirmed colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency, or TRAPS at the time of a flare to receive 150 mg of canakinumab subcutaneously or placebo every 4 weeks. Patients who did not have a resolution of their flare received an add-on injection of 150 mg of canakinumab. Read More

    Neuroimaging Findings of Organic Acidemias and Aminoacidopathies.
    Radiographics 2018 May-Jun;38(3):912-931
    From the Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science (N.R., S.F.C., T.A.G.M.H., B.P.S.), and McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics (H.J.V.), The Johns Hopkins University School of Medicine, Charlotte R. Bloomberg Children's Center Bldg, Sheikh Zayed Tower, Room 4174, 1800 Orleans St, Baltimore, MD 21287-0842; Università degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan, Italy (S.F.C.); Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, Md (H.J.V.); and Department of Pediatric Neurology, University Children's Hospital of Zurich, Zurich, Switzerland (E.B.).
    Although individual cases of inherited metabolic disorders are rare, overall they account for a substantial number of disorders affecting the central nervous system. Organic acidemias and aminoacidopathies include a variety of inborn errors of metabolism that are caused by defects in the intermediary metabolic pathways of carbohydrates, amino acids, and fatty acid oxidation. These defects can lead to the abnormal accumulation of organic acids and amino acids in multiple organs, including the brain. Read More

    Status of Newborn Screening and Inborn Errors of Metabolism in India.
    Indian J Pediatr 2018 May 7. Epub 2018 May 7.
    Department of Genetics, University of Delhi, South Campus, New Delhi, India.
    Inborn errors of metabolism (IEM) are a heterogeneous group of genetic disorders that cause significant neonatal and infant mortality. Expanded newborn screening which detects these disorders at birth is the standard preventive strategy in most countries. Prospective studies to evaluate the impact of these in the Indian population are lacking. Read More

    Movement Disorders and Neurometabolic Diseases.
    Semin Pediatr Neurol 2018 Apr 14;25:82-91. Epub 2018 Feb 14.
    Department of Neurology, Section of Child Neurology, Indiana University School of Medicine, Indianapolis, IN; Department of Pediatrics, Section of Developmental Pediatrics, Indiana University School of Medicine, Indianapolis, IN; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN.
    Many inherited metabolic diseases or inborn errors of metabolism (IEM) cause movement disorders in children. This review focuses on chorea, dystonia, myoclonus, tremor, and parkinsonism. Broad neurometabolic categories commonly responsible for pediatric movement disorders include mitochondrial cytopathies, organic acidemias, mineral metabolism and transport disorders, neurotransmitter diseases, purine metabolism abnormalities, lipid storage conditions, and creatine metabolism dysfunction. Read More

    Integration of genomics and metabolomics for prioritization of rare disease variants: a 2018 literature review.
    J Inherit Metab Dis 2018 May 2. Epub 2018 May 2.
    BC Children's Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
    Many inborn errors of metabolism (IEMs) are amenable to treatment; therefore, early diagnosis and treatment is imperative. Despite recent advances, the genetic basis of many metabolic phenotypes remains unknown. For discovery purposes, whole exome sequencing (WES) variant prioritization coupled with clinical and bioinformatics expertise is the primary method used to identify novel disease-causing variants; however, causation is often difficult to establish due to the number of plausible variants. Read More

    Diagnostic potential of stored dried blood spots for inborn errors of metabolism: a metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency.
    J Clin Pathol 2018 May 2. Epub 2018 May 2.
    Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
    Aim: It is estimated that 1-5% of sudden infant death syndrome (SIDS) cases might be caused by undiagnosed inborn errors of metabolism (IEMs); however, the postmortem identification of IEMs remains difficult. This study aimed to evaluate the usefulness of dried blood spots (DBSs) stored after newborn screening tests as a metabolic autopsy to determine the causes of death in infants and children who died suddenly and unexpectedly.

    Methods: Infants or toddlers who had suddenly died without a definite diagnosis between July 2008 and December 2012 at Kyushu University Hospital in Japan were enrolled in this study. Read More

    Association of Lonafarnib Treatment vs No Treatment With Mortality Rate in Patients With Hutchinson-Gilford Progeria Syndrome.
    JAMA 2018 04;319(16):1687-1695
    Division of Hematology/Oncology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
    Importance: Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare fatal premature aging disease. There is no approved treatment.

    Objective: To evaluate the association of monotherapy using the protein farnesyltransferase inhibitor lonafarnib with mortality rate in children with HGPS. Read More

    Study of Intraventricular Cerliponase Alfa for CLN2 Disease.
    N Engl J Med 2018 05 24;378(20):1898-1907. Epub 2018 Apr 24.
    From the Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (A.S., A.K.); BioMarin Pharmaceutical, Novato, CA (T.A., H.C., P.S., D.J.); the Department of Neuroscience, Bambino Gesù Children's Hospital, IRCCS, Rome (N.S.); Nationwide Children's Hospital and Ohio State University, Columbus (E.L.R.); UCL Great Ormond Street Institute of Child Health, London (P.G.); and the Citigroup Biomedical Imaging Center, Departments of Radiology and Genetic Medicine, Weill Cornell Medical College, New York (D.B., J.P.D.).
    Background: Recombinant human tripeptidyl peptidase 1 (cerliponase alfa) is an enzyme-replacement therapy that has been developed to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal disorder that causes progressive dementia in children.

    Methods: In a multicenter, open-label study, we evaluated the effect of intraventricular infusion of cerliponase alfa every 2 weeks in children with CLN2 disease who were between the ages of 3 and 16 years. Treatment was initiated at a dose of 30 mg, 100 mg, or 300 mg; all the patients then received the 300-mg dose for at least 96 weeks. Read More

    Mutational spectrum of PTS gene and in silico pathological assessment of a novel variant in Mexico.
    Brain Dev 2018 Apr 20. Epub 2018 Apr 20.
    Laboratory of Inborn Errors of Metabolism and Screening, National Institute of Pediatrics, Mexico City, Mexico. Electronic address:
    Background: Tetrahydrobiopterin (BH4) is the cofactor for 6-pyruvoyl-tetrahydropterin synthase (PTPS); it is involved in BH4 biosynthesis and is encoded by PTS gene. Its deficiency (PTPSD) is characterized by hyperphenylalaninemia (HPA) and deficit in central monoamine neurotransmitters. We describe the clinical and mutational spectrum of five patients with PTPSD, from four unrelated Mexican families. Read More

    Multiplex tandem mass spectrometry assay for newborn screening of X-linked adrenoleukodystrophy, biotinidase deficiency, and galactosemia with flexibility to assay other enzyme assays and biomarkers.
    Mol Genet Metab 2018 Jun 29;124(2):101-108. Epub 2018 Mar 29.
    Departments of Chemistry, University of Washington, Seattle, WA 98195, USA; Departments of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address:
    All States screen for biotinidase deficiency and galactosemia, and X-linked adrenoleukodystrophy (X-ALD) has recently been added to the Recommended Uniform Screening Panel (RUSP).We sought to consolidate these tests by combining them into a single multiplex tandem mass spectrometry assay as well as to improve the current protocol for newborn screening of galactosemia.A 3 mm punch of a dried blood spot (DBS) was extracted with organic solvent for analysis of the C26:0-lysophosphatidylcholine biomarker for X-ALD. Read More

    Methyl-ketones in the scent glands of Opiliones: a chemical trait of cyphophthalmi retrieved in the dyspnoan .
    Chemoecology 2018 6;28(2):61-67. Epub 2018 Apr 6.
    1Institute of Biology, University Graz, Universitätsplatz 2, 8010 Graz, Austria.
    The homologous and phylogenetically old scent glands of harvestmen-also called defensive or repugnatorial glands-represent an ideal system for a model reconstruction of the evolutionary history of exocrine secretion chemistry ("phylogenetic chemosystematics"). While the secretions of Laniatores (mainly phenols, benzoquinones), Cyphophthalmi (naphthoquinones, chloro-naphthoquinones, methyl-ketones) and some Eupnoi (naphthoquinones, ethyl-ketones) are fairly well studied, one open question refers to the still largely enigmatic scent gland chemistry of representatives of the suborder Dyspnoi and the relation of dyspnoan chemistry to the remaining suborders. We here report on the secretion of a nemastomatid Dyspnoi, which is composed of straight-chain methyl-ketones (heptan-2-one, nonan-2-one, 6-tridecen-2-one, 8-tridecen-2-one), methyl-branched methyl-ketones (5-methyl-heptan-2-one, 6-methyl-nonan-2-one), naphthoquinones (1,4-naphthoquinone, 6-methyl-1,4-naphthoquinone) and chloro-naphthoquinones (4-chloro-1,2-naphthoquinone, 4-chloro-6-methyl-1,2-naphthoquinone). Read More

    Transcobalamin receptor defect: Identification of two new cases through positive newborn screening for propionic/methylmalonic aciduria and long-term outcome.
    Am J Med Genet A 2018 Jun 16;176(6):1411-1415. Epub 2018 Apr 16.
    Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
    Likely pathogenic variants in CD320 cause transcobalamin receptor defect, a recently discovered inborn errors of cobalamin metabolism. Only 12 cases have been reported to date. There are no long-term clinical and biochemical outcome reports since its first description. Read More

    Crossing barriers: a multidisciplinary approach to children and adults with young-onset movement disorders.
    J Clin Mov Disord 2018 6;5. Epub 2018 Apr 6.
    1Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
    Background: Diagnosis of less common young-onset movement disorders is often challenging, requiring a broad spectrum of skills of clinicians regarding phenotyping, normal and abnormal development and the wide range of possible acquired and genetic etiologies. This complexity often leads to considerable diagnostic delays, paralleled by uncertainty for patients and their families. Therefore, we hypothesized that these patients might benefit from a multidisciplinary approach. Read More

    Inborn Errors of Metabolism in the Emergency Department (Undiagnosed and Management of the Known).
    Emerg Med Clin North Am 2018 May;36(2):369-385
    Pediatric Emergence Medicine, Carolinas HealthCare System, 1000 Blythe Boulevard, 3rd Floor MEB, Charlotte, NC 28203, USA.
    An inborn error of metabolism should be considered in any neonate who presents to the emergency department in extremis and in any young child who presents with altered mental status and vomiting. In children with unknown diagnoses, it is crucial to draw the appropriate laboratory studies before the institution of therapy, although treatment needs rapid institution to mitigate neurologic damage and avoid worsening metabolic crisis. Although there are hundreds of individual genetic disorders, they are roughly placed into groups that present similarly. Read More

    The Frequency of Infective Endocarditis in Candida Bloodstream Infections: a Retrospective Study in a Child Hospital.
    Braz J Cardiovasc Surg 2018 Jan-Feb;33(1):54-58
    Department of Pediatric Infectious Diseases, Dr. Behçet Uz Children's Hospital, İzmir, Turkey.
    Introduction: Fungal endocarditis is reported less frequently than bacterial endocarditis, with an incidence of 0-12% of the total pediatric infective endocarditis.

    Objective: In this study, the incidence of infective endocarditis in Candida bloodstream infections in a tertiary hospital during the periods of 2007 and 2016 was reviewed.

    Methods: Patients with positive blood or catheter cultures in terms of Candida spp. Read More

    Pregnancy management and outcome in patients with four different tetrahydrobiopterin disorders.
    J Inherit Metab Dis 2018 Mar 28. Epub 2018 Mar 28.
    Division of Child Neurology and Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
    Introduction: Inborn errors of tetrahydrobiopterin (BH) biosynthesis or recycling are a group of very rare neurometabolic diseases. Following growing awareness and improved availability of drug treatment the number of patients with BH disorders reaching adulthood is constantly increasing. Pregnancy care of patients with these disorders is therefore a new challenge for clinicians. Read More

    Bi-allelic Mutations in EPRS, Encoding the Glutamyl-Prolyl-Aminoacyl-tRNA Synthetase, Cause a Hypomyelinating Leukodystrophy.
    Am J Hum Genet 2018 Apr 22;102(4):676-684. Epub 2018 Mar 22.
    Child Health and Human Development Program, Research Institute of the McGill University Health Center, Montreal, QC H4A 3J1, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, QC H4A 3J1, Canada; Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada; Department of Medical Genetics, Montreal Children's Hospital, McGill University Health Center, Montreal, QC H4A 3J1, Canada. Electronic address:
    Hypomyelinating leukodystrophies are genetic disorders characterized by insufficient myelin deposition during development. They are diagnosed on the basis of both clinical and MRI features followed by genetic confirmation. Here, we report on four unrelated affected individuals with hypomyelination and bi-allelic pathogenic variants in EPRS, the gene encoding cytoplasmic glutamyl-prolyl-aminoacyl-tRNA synthetase. Read More

    Classic infantile Pompe patients approaching adulthood: a cohort study on consequences for the brain.
    Dev Med Child Neurol 2018 06 24;60(6):579-586. Epub 2018 Mar 24.
    Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
    Aim: To examine the long-term consequences of glycogen storage in the central nervous system (CNS) for classic infantile Pompe disease using enzyme replacement therapy.

    Method: Using neuropsychological tests and brain magnetic resonance imaging (MRI), we prospectively assessed a cohort of 11 classic infantile Pompe patients aged up to 17 years.

    Results: From approximately age 2 years onwards, brain MRI showed involvement of the periventricular white matter and centrum semiovale. Read More

    Pediatric endocrine and metabolic diseases and proteomics.
    J Proteomics 2018 Mar 18. Epub 2018 Mar 18.
    Proteomics Research Unit, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
    The principles of Predictive, Preventive and Personalized Medicine (PPPM) dictate the need to recognize individual susceptibility to disease in a timely fashion and to offer targeted preventive interventions and treatments. Proteomics is a state-of-the art technology- driven science aiming at expanding our understanding of the pathophysiologic mechanisms that underlie disease, but also at identifying accurate predictive, diagnostic and therapeutic biomarkers, that will eventually promote the implementation of PPPM. In this review, we summarize the wide spectrum of the applications of Mass Spectrometry-based proteomics in the various fields of Pediatric Endocrinology, including Inborn Errors of Metabolism, type 1 diabetes, Adrenal Disease, Metabolic Syndrome and Thyroid disease, ranging from neonatal screening to early recognition of specific at-risk populations for disease manifestations or complications in adult life and to monitoring of disease progression and response to treatment. Read More

    Laboratory analysis of organic acids, 2018 update: a technical standard of the American College of Medical Genetics and Genomics (ACMG).
    Genet Med 2018 Mar 15. Epub 2018 Mar 15.
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
    Disclaimer: These ACMG Standards are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards is voluntary and does not necessarily assure a successful medical outcome. These Standards should not be considered inclusive of all proper procedures and tests, or exclusive of others that are reasonably directed to obtaining the same results. Read More

    Benchmarking of Four Near Infrared Spectroscopy Devices for Long Time Use in Neonates.
    Klin Padiatr 2018 Mar 14. Epub 2018 Mar 14.
    Division of Neonatology, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
    Background: Using near-infrared spectroscopy (NIRS) mixed tissue saturation can be calculated by measuring the oxygen saturation of oxygenated and deoxygenated erythrocytes in the tissue. Quality of the calculated value is not only dependent on the exposure of the measured values in the calculation, but also on external factors such as artifacts. Main object of this study was to determine whether and how the measurement quality of different devices varies in their long-term use in premature infants. Read More

    Multiomics tools for the diagnosis and treatment of rare neurological disease.
    J Inherit Metab Dis 2018 May 13;41(3):425-434. Epub 2018 Mar 13.
    Division of Child Neurology, University Children's Hospital Zurich, Zurich, Switzerland.
    Conventional workup of rare neurological disease is frequently hampered by diagnostic delay or lack of diagnosis. While biomarkers have been established for many neurometabolic disorders, improved methods are required for diagnosis of previously unidentified or underreported causes of rare neurological disease. This would result in a higher diagnostic yield and increased patient numbers required for interventional studies. Read More

    Lysosomal Acid Lipase Deficiency: Report of Five Cases across the Age Spectrum.
    Case Rep Pediatr 2018 21;2018:4375434. Epub 2018 Jan 21.
    Reference Center for Inborn Errors of Metabolism (CREIM), Department of Pediatrics, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
    Lysosomal acid lipase (LAL) deficiency is an autosomal recessive lysosomal storage disorder caused by mutations in the gene that leads to premature organ damage and mortality. We present retrospective data from medical records of 5 Brazilian patients, showing the broad clinical spectrum of the disease. Read More

    Pharmacokinetics and pharmacodynamics of PEGylated truncated human cystathionine beta-synthase for treatment of homocystinuria.
    Life Sci 2018 May 9;200:15-25. Epub 2018 Mar 9.
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address:
    Aims: PEGylated human truncated cystathionine beta-synthase, lacking the C-terminal regulatory domain (PEG-CBS), is a promising preclinical candidate for enzyme replacement therapy in homocystinuria (HCU). It was designed to function as a metabolic sink to decrease the severely elevated plasma and tissue homocysteine concentrations. In this communication, we evaluated pharmacokinetics (PK), pharmacodynamics (PD) and sub-chronic toxicity of PEG-CBS in homocystinuric mice, wild type rats and monkeys to estimate the minimum human efficacious dose for clinical trials. Read More

    Diagnosis and Management of Gaucher Disease in India - Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics.
    Indian Pediatr 2018 02;55(2):143-153
    Metabolic Liver and Lysosomal Disease Program, Yale University School of Medicine, New Haven, USA.
    Justification: Gaucher disease (GD) is amongst the most frequently occurring lysosomal storage disorder in all ethnicities. The clinical manifestations and natural history of GD is highly heterogeneous with extreme geographic and ethnic variations. The literature on GD has paucity of information and optimal management guidelines for Indian patients. Read More

    Newborn Screening: History, Current Status, and Future Directions.
    Pediatr Clin North Am 2018 Apr 28;65(2):389-405. Epub 2017 Dec 28.
    Department of Molecular and Human Genetics, Baylor College of Medicine, Texas Children's Hospital, One Baylor Plaza, Houston, TX 77030, USA. Electronic address:
    Newborn screening programs aim to achieve presymptomatic diagnosis of treatable disorders allowing for early initiation of medical care to prevent or reduce significant morbidity and mortality. Many of the conditions included in the newborn screening panels are inborn errors of metabolism; however, screening for endocrine, hematologic, immunologic, and cardiovascular diseases, and hearing loss is also included in many panels. Newborn screening tests are not diagnostic and therefore diagnostic testing is needed to confirm or exclude the suspected diagnosis. Read More

    Complex Phenotypes in Inborn Errors of Metabolism: Overlapping Presentations in Congenital Disorders of Glycosylation and Mitochondrial Disorders.
    Pediatr Clin North Am 2018 Apr;65(2):375-388
    Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium; Hayward Genetics Center, Tulane University Medical School, New Orleans, LA, USA. Electronic address:
    Congenital disorders of glycosylation (CDG) and mitochondrial disorders have overlapping clinical features, including central nervous system, cardiac, gastrointestinal, hepatic, muscular, endocrine, and psychiatric disease. Specific abnormalities orienting the clinician toward the right diagnostic approach include abnormal fat distribution, coagulation abnormalities, together with anticoagulation abnormalities, hyperinsulinism, and congenital malformations in CDG. Diabetes, sensorineural deafness, and depression are very rare in CDG but common in mitochondrial disease. Read More

    Inborn Errors of Metabolism with Myopathy: Defects of Fatty Acid Oxidation and the Carnitine Shuttle System.
    Pediatr Clin North Am 2018 Apr 28;65(2):317-335. Epub 2017 Dec 28.
    Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address:
    Fatty acid oxidation disorders (FAODs) and carnitine shuttling defects are inborn errors of energy metabolism with associated mortality and morbidity due to cardiomyopathy, exercise intolerance, rhabdomyolysis, and liver disease with physiologic stress. Hypoglycemia is characteristically hypoketotic. Lactic acidemia and hyperammonemia may occur during decompensation. Read More

    Inborn Errors of Metabolism with Seizures: Defects of Glycine and Serine Metabolism and Cofactor-Related Disorders.
    Pediatr Clin North Am 2018 Apr 28;65(2):279-299. Epub 2017 Dec 28.
    Division of Clinical Genetics and Metabolic Disorders, Pediatrics Department, Tawam Hospital, Tawam Roundabout, Al-Ain 15258, United Arab Emirates. Electronic address:
    Inborn errors of metabolism (IEM) are relatively uncommon causes for seizures in children; however, they should be considered in the differential diagnosis because several IEM are potentially treatable and seizures can be resolved if appropriate treatment is initiated. Clues from clinical presentation, physical examination, laboratory tests, and brain imaging can raise the possibility of IEM. Several IEM can present with seizures, either as the main presenting finding or as a part of a more complex phenotype. Read More

    Inborn Errors of Metabolism with Cognitive Impairment: Metabolism Defects of Phenylalanine, Homocysteine and Methionine, Purine and Pyrimidine, and Creatine.
    Pediatr Clin North Am 2018 Apr;65(2):267-277
    Division of Medical Genetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address:
    Phenylketonuria is a defect in phenylalanine metabolism resulting in the excretion of phenylketones and severe intellectual disability. The principle of eliminating the offending amino acid from the diet as a successful treatment strategy was demonstrated. The development of a low methionine diet to treat homocystinuria was established after identifying the transsulfuration pathway resulting in cysteine synthesis. Read More

    Metabolomics Profile in ABAT Deficiency Pre- and Post-treatment.
    JIMD Rep 2018 Feb 27. Epub 2018 Feb 27.
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
    Metabolomic profiling is an emerging technology in the clinical setting with immediate diagnostic potential for the population of patients with Inborn Errors of Metabolism. We present the metabolomics profile of two ABAT deficiency patients both pre- and posttreatment with flumazenil. ABAT deficiency, also known as GABA-transaminase deficiency, is caused by recessive mutations in the gene ABAT and leads to encephalopathy of variable severity with hypersomnolence, hypotonia, hypomyelination, and seizures. Read More

    Metabolic causes of nonimmune hydrops fetalis: A next-generation sequencing panel as a first-line investigation.
    Clin Chim Acta 2018 Jun 22;481:1-8. Epub 2018 Feb 22.
    Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76000, France; Normandie Univ, UNIROUEN, CHU Rouen, INSERM U1245, 76000 Rouen, France. Electronic address:
    Purposes: Hydrops fetalis is a life-threatening fetal condition, and 85% of all cases are classified as nonimmune hydrops fetalis (NIHF). Up to 15% of NIHF cases may be due to inborn errors of metabolism (IEM), but a large proportion of cases linked to metabolic disorders remains undiagnosed. This lack of diagnosis may be related to the limitations of conventional biological procedures, which involve sequential investigations and require multiple samples and steps. Read More

    Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection.
    Cell 2018 Feb;172(5):952-965.e18
    St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris 75015, France; Paris Descartes University, Imagine Institute, Paris 75015, France; Howard Hughes Medical Institute, New York, NY 10065, USA; Pediatric Immunology-Hematology Unit, Necker Hospital for Sick Children, Paris 75015, France.
    Viruses that are typically benign sometimes invade the brainstem in otherwise healthy children. We report bi-allelic DBR1 mutations in unrelated patients from different ethnicities, each of whom had brainstem infection due to herpes simplex virus 1 (HSV1), influenza virus, or norovirus. DBR1 encodes the only known RNA lariat debranching enzyme. Read More

    The Essential Role of Primary Caregiver in Early Detection of Familial Hypercholesterolemia and Cardiovascular Prevention.
    Curr Pediatr Rev 2017 ;13(4):260-264
    Department of Medicine, McGill University, Montreal, Quebec, Canada.
    Familial hypercholesterolemia (FH) is a worldwide common autosomal inherited condition associated with premature cardiovascular diseases, both in men and in women (World frequency has been recently estimated to be as high as 1:250). Identifying FH cases early in life could represent a cornerstone to prevent fatal events in adult's life. Pediatricians are well positioned to evaluate the familial cardiovascular risk factors among their young patients, to make a diagnosis and to perform familial screening. Read More

    Next-generation metabolic screening: targeted and untargeted metabolomics for the diagnosis of inborn errors of metabolism in individual patients.
    J Inherit Metab Dis 2018 May 16;41(3):337-353. Epub 2018 Feb 16.
    Department of Laboratory Medicine, Translational Metabolic Laboratory (TML), Radboud University Medical Center, Geert Groote Plein Zuid 10, 6525, GA, Nijmegen, The Netherlands.
    The implementation of whole-exome sequencing in clinical diagnostics has generated a need for functional evaluation of genetic variants. In the field of inborn errors of metabolism (IEM), a diverse spectrum of targeted biochemical assays is employed to analyze a limited amount of metabolites. We now present a single-platform, high-resolution liquid chromatography quadrupole time of flight (LC-QTOF) method that can be applied for holistic metabolic profiling in plasma of individual IEM-suspected patients. Read More

    Hypomyelinating disorders in China: The clinical and genetic heterogeneity in 119 patients.
    PLoS One 2018 16;13(2):e0188869. Epub 2018 Feb 16.
    Department of Pediatrics, Peking University First Hospital, Beijing, China.
    Objective: Hypomyelinating disorders are a group of clinically and genetically heterogeneous diseases characterized by neurological deterioration with hypomyelination visible on brain MRI scans. This study was aimed to clarify the clinical and genetic features of HMDs in Chinese population.

    Methods: 119 patients with hypomyelinating disorders in Chinese population were enrolled and evaluated based on their history, clinical manifestation, laboratory examinations, series of brain MRI with follow-up, genetic etiological tests including chromosomal analysis, multiplex ligation probe amplification, Sanger sequencing, targeted enrichment-based next-generation sequencing and whole exome sequencing. Read More

    The functional genomics laboratory: functional validation of genetic variants.
    J Inherit Metab Dis 2018 May 14;41(3):297-307. Epub 2018 Feb 14.
    Radboudumc, Radboud Center for Mitochondrial Medicine, 774 Translational Metabolic Laboratory, Department of Pediatrics, PO Box 9101, 6500HB, Nijmegen, The Netherlands.
    Currently, one of the main challenges in human molecular genetics is the interpretation of rare genetic variants of unknown clinical significance. A conclusive diagnosis is of importance for the patient to obtain certainty about the cause of the disease, for the clinician to be able to provide optimal care to the patient and to predict the disease course, and for the clinical geneticist for genetic counseling of the patient and family members. Conclusive evidence for pathogenicity of genetic variants is therefore crucial. Read More

    Secondary Hemophagocytic Syndrome Associated with COG6 Gene Defect: Report and Review.
    JIMD Rep 2018 Feb 15. Epub 2018 Feb 15.
    King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs (NGHA), Riyadh, Saudi Arabia.
    Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially fatal disease that is characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes. Clinically, it is characterized by prolonged fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, pancytopenia, and hemophagocytosis in the bone marrow, spleen, or lymph nodes. It can be classified as primary if it is due to a genetic defect, or secondary if it is due to a different etiology such as severe infection, immune deficiency syndrome, rheumatological disorder, malignancy, and inborn errors of metabolism such as galactosemia, multiple sulfatase deficiency, lysinuric protein intolerance, Gaucher disease, Niemann-Pick disease, Wolman disease, propionic acidemia, methylmalonic acidemia, biotinidase deficiency, cobalamin C defect, galactosialidosis, Pearson syndrome, and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. Read More

    Argininemia as a cause of severe chronic stunting and partial growth hormone deficiency (PGHD): A case report.
    Medicine (Baltimore) 2018 Feb;97(7):e9880
    Department of Pediatrics, West China Second University Hospital.
    Rationale: Argininemia is an autosomal recessive inherited disorder of the urea cycle. Because of its atypical symptoms in early age, diagnosis can be delayed until the typical chronic manifestations - including spastic diplegia, deterioration in cognitive function, and epilepsy - appear in later childhood.

    Patient Concerns: A Chinese boy initially presented with severe stunting and partial growth hormone deficiency (PGHD) at 3 years old and was initially treated with growth hormone replacement therapy. Read More

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