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    12126 results match your criteria Pediatrics Inborn Errors of Metabolism

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    Next-generation metabolic screening: targeted and untargeted metabolomics for the diagnosis of inborn errors of metabolism in individual patients.
    J Inherit Metab Dis 2018 Feb 16. 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

    The functional genomics laboratory: functional validation of genetic variants.
    J Inherit Metab Dis 2018 Feb 14. 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

    Peroxisomal disorders: Improved laboratory diagnosis, new defects and the complicated route to treatment.
    Mol Cell Probes 2018 Feb 10. Epub 2018 Feb 10.
    Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands; Department of Pediatrics, Laboratory Genetic Metabolic Diseases, Emma Children's Hospital, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address:
    Peroxisomes catalyze a number of essential metabolic functions of which fatty acid alpha- and beta-oxidation, ether phospholipid biosynthesis, glyoxylate detoxification and bile acid synthesis are the most important. The key role of peroxisomes in humans is exemplified by the existence of a group of peroxisomal disorders, caused by mutations in > 30 different genes which codes for proteins with a role in either peroxisome biogenesis or one of the metabolic pathways in peroxisomes. Technological advances in laboratory methods at the metabolite-, enzyme-, and molecular level has not only allowed the identification of a new peroxisomal disorder but also new phenotypes associated with already identified genetic defects thus extending the clinical spectrum. Read More

    From rodent heart to inborn errors of human metabolism.
    Mol Genet Metab 2018 Feb 5. Epub 2018 Feb 5.
    Centre for Molecular Medicine and Therapeutics, Vancouver, BC, Canada; Department of Pediatrics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada; Department of Pediatrics, Academic Medical Centre, Amsterdam, The Netherlands; Department of Clinical Genetics, Academic Medical Centre, Amsterdam, The Netherlands.

    Diacerein Orphan Drug Development for Epidermolysis Bullosa Simplex: A Phase 2/3 Randomized, Placebo-Controlled, Double-Blind Clinical Trial.
    J Am Acad Dermatol 2018 Feb 1. Epub 2018 Feb 1.
    Dept. of Dermatology, University Hospital Salzburg, Paracelsus Medical University Salzburg, Austria.
    Background: EBS is a rare genetic, blistering skin disease for which there is no cure. Treatments that address the pathophysiology of EBS are needed.

    Objective: Compare the impact of 1% diacerein cream vs placebo in reducing blister number in EBS. Read More

    Inborn errors of metabolism and the human interactome: a systems medicine approach.
    J Inherit Metab Dis 2018 Feb 5. Epub 2018 Feb 5.
    Department of Molecular Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Lindwurmstrasse 4, 80336, Munich, Germany.
    The group of inborn errors of metabolism (IEM) displays a marked heterogeneity and IEM can affect virtually all functions and organs of the human organism; however, IEM share that their associated proteins function in metabolism. Most proteins carry out cellular functions by interacting with other proteins, and thus are organized in biological networks. Therefore, diseases are rarely the consequence of single gene mutations but of the perturbations caused in the related cellular network. Read More

    A novel method for quantitation of acylglycines in human dried blood spots by UPLC-tandem mass spectrometry.
    Clin Biochem 2018 Feb 2. Epub 2018 Feb 2.
    Newborn Screening Ontario, Children's Hospital of Eastern Ontario, 415 Smyth Road, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada; University of Ottawa, Department of Pediatrics, 451 Smyth Road, Ottawa, Ontario, Canada; University of Ottawa, Department of Pathology and Laboratory Medicine, 451 Smyth Road, Ottawa, Ontario, Canada.
    Background: Several acylcarnitines used as primary markers on dried blood filter papers (DBS) for newborn screening lack specificity and contribute to a higher false positive rate. The analysis of urine acylglycines is useful in the diagnosis of inborn errors of metabolism (IEM) including medium chain acyl-CoA dehydrogenase deficiency (MCADD), isovaleric acidemia, and beta-ketothiolase deficiency (BKTD). Currently, no method for analyzing acylglycines from DBS has been published. Read More

    Creatine Transporter Deficiency in Two Brothers with Autism Spectrum Disorder.
    Indian Pediatr 2018 Jan;55(1):67-68
    Department of Pediatrics, Medical Faculty, Section of Inborn Errors of Metabolism, Baskent University, Ankara, Turkey. Correspondence to: Dr Halil Ibrahim Aydin, Professor, Baskent University Medical Faculty, Department of Pediatrics, Section of Inborn Errors of Metabolism, Temel Kuguluoglu Sokak, No: 24/2, Bahçelievler, Ankara, Turkey.
    Background: Creatine transporter deficiency (CTD) is a treatable, X-linked, inborn error of metabolism.

    Case Characteristics: Two brothers with autism spectrum disorder were diagnosed with CTD at the ages of 17 and 12 years. Both were found to have a previously reported hemizygous p. Read More

    Renal replacement therapy in the neonatal intensive care unit.
    Pediatr Neonatol 2017 Dec 21. Epub 2017 Dec 21.
    Division of Neonatology, Department of Pediatrics, Chang Gung Memorial Hospital Linkou Branch and School of Medicine, Chang Gung University, No. 5, Fuxing St., Guishan Dist., Taoyuan City 333, Taiwan, ROC. Electronic address:
    Background: Renal replacement therapy (RRT) is becoming increasingly necessary for supporting critically ill neonates. Few studies have reported the use of RRT in the neonatal intensive care unit (NICU). Therefore, we performed a retrospective study to describe the use of RRT in our NICU and its associated efficacy, complications, and outcomes. Read More

    Infantile-onset Pompe disease with neonatal debut: A case report and literature review.
    Medicine (Baltimore) 2017 Dec;96(51):e9186
    Department of Neonatology-Pediatrics.
    Rationale: Infantile-onset Pompe disease, also known as glycogen storage disease type II, is a progressive and fatal disorder without treatment. Enzyme replacement therapy with recombinant human acid alpha-glucosidase (GAA) enhances survival; however, the best outcomes have been achieved with early treatment.

    Patient Concerns: We report a case of a newborn with infantile-onset Pompe disease diagnosed in the first days of life who did not undergo universal neonatal screening. Read More

    The impact of consanguinity on the frequency of inborn errors of metabolism.
    Mol Genet Metab Rep 2018 Jun 11;15:6-10. Epub 2018 Jan 11.
    Centre for Inherited Metabolic Diseases, Departments of Pediatrics and Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Inborn errors of metabolism (IEM) are a heterogeneous group of genetic disorders present in all ethnic groups. We investigated the frequency of consanguinity among parents of newborns with IEM diagnosed by neonatal screening. Data were obtained from 15 years of expanded newborn screening for selected IEM with autosomal recessive mode of inheritance, a national screening program of newborns covering the period from 2002 until April 2017. Read More

    Recent perspectives of pediatric mitochondrial diseases.
    Exp Ther Med 2018 Jan 27;15(1):13-18. Epub 2017 Oct 27.
    Department of Neonatology, Xuzhou Children's Hospital, Xuzhou, Jiangsu 221002, P.R. China.
    Mitochondrial disorders are amongst the most common groups of inborn errors of metabolism. They are caused by deficiencies in the final pathway of the cellular energy production, the mitochondrial respiratory chain. The disorders are clinically and genetically heterogeneous and the aetiology could be found in the mitochondrial, or in the nuclear genome. Read More

    "Transcriptomics": molecular diagnosis of inborn errors of metabolism via RNA-sequencing.
    J Inherit Metab Dis 2018 Jan 25. Epub 2018 Jan 25.
    Institute of Human Genetics, Technische Universität München, Trogerstrasse 32, 81675, Munich, Germany.
    Exome wide sequencing techniques have revolutionized molecular diagnostics in patients with suspected inborn errors of metabolism or neuromuscular disorders. However, the diagnostic yield of 25-60% still leaves a large fraction of individuals without a diagnosis. This indicates a causative role for non-exonic regulatory variants not covered by whole exome sequencing. Read More

    International practices in the dietary management of fructose 1-6 biphosphatase deficiency.
    Orphanet J Rare Dis 2018 Jan 25;13(1):21. Epub 2018 Jan 25.
    Birmingham Women's and Children's Hospital, Birmingham, UK.
    Background: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. Read More

    Mitochondrial translation requires folate-dependent tRNA methylation.
    Nature 2018 Feb 24;554(7690):128-132. Epub 2018 Jan 24.
    Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
    Folates enable the activation and transfer of one-carbon units for the biosynthesis of purines, thymidine and methionine. Antifolates are important immunosuppressive and anticancer agents. In proliferating lymphocytes and human cancers, mitochondrial folate enzymes are particularly strongly upregulated. Read More

    Efficacy of Peritoneal Dialysis in Neonates Presenting With Hyperammonaemia Due to Urea Cycle Defects and Organic Acidaemia.
    Nephrology (Carlton) 2018 Jan 22. Epub 2018 Jan 22.
    Diyarbakir Children's Hospital, Department of Pediatrics, Division of Pediatric Neurology, Diyarbakir, Turkey.
    Aim: Newborns with inborn errors of metabolism can present with hyperammonaemic coma. In this study, we evaluated the effect of peritoneal dialysis on plasma ammonium levels and on the short-term outcome in neonatal patients with urea cycle defects and organic acidaemia.

    Methods: Data from infants with hyperammonaemia due to urea cycle defects or organic acidaemia treated with dialysis were collected and retrospectively analysed. Read More

    Disorders of metal metabolism.
    Transl Sci Rare Dis 2017 Dec 18;2(3-4):101-139. Epub 2017 Dec 18.
    Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
    Trace elements are chemical elements needed in minute amounts for normal physiology. Some of the physiologically relevant trace elements include iodine, copper, iron, manganese, zinc, selenium, cobalt and molybdenum. Of these, some are metals, and in particular, transition metals. Read More

    Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis.
    J Inherit Metab Dis 2018 Jan 16. Epub 2018 Jan 16.
    Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Room 3109, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada.
    Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze phenotypes. Such methods have allowed phenotypic data to be widely used in medical applications, from assisting clinical diagnoses to prioritizing genomic diagnoses. Read More

    Early neonatal Glutaric aciduria type I hidden by perinatal asphyxia: a case report.
    Ital J Pediatr 2018 Jan 15;44(1). Epub 2018 Jan 15.
    Pediatric Neurology Unit, "Vittore Buzzi" Children's Hospital, ASST FBF-Sacco, Milan, Italy.
    Background: Perinatal asphyxia (PA) occurs in about 2 to 10 per 1000 live full-term births. Although neonatal epileptic seizures are observed in up to 60% of cases, PA may mimic or subtend other conditions. Hypoxia related brain injury is particularly relevant, as it may have permanent effects on neuropsychomotor development. Read More

    Correction to: Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders.
    J Inherit Metab Dis 2018 Jan 12. Epub 2018 Jan 12.
    Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
    Due to an unfortunate error during the typesetting process, the collaborators were presented incorrectly. Read More

    Flux analysis of inborn errors of metabolism.
    J Inherit Metab Dis 2018 Jan 9. Epub 2018 Jan 9.
    Section of Systems Medicine and Metabolic Signaling, Laboratory of Pediatrics, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
    Patients with an inborn error of metabolism (IEM) are deficient of an enzyme involved in metabolism, and as a consequence metabolism reprograms itself to reach a new steady state. This new steady state underlies the clinical phenotype associated with the deficiency. Hence, we need to know the flux of metabolites through the different metabolic pathways in this new steady state of the reprogrammed metabolism. Read More

    APRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients.
    Nat Commun 2018 01 4;9(1):67. Epub 2018 Jan 4.
    Department of Human Genetics, McGill University and Research Institute McGill University Health Centre, Montreal, H4A 3J1, Quebec, Canada.
    To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin Bmetabolism that we name "epi-cblC". The subjects are compound heterozygotes for a genetic mutation and for a promoter epimutation, detected in blood, fibroblasts, and sperm, at the MMACHC locus; 5-azacytidine restores the expression of MMACHC in fibroblasts. Read More

    Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care.
    Genet Med 2018 Jan 4. Epub 2018 Jan 4.
    Clinical Genetics Unit, Department of Obstetrics and Pediatrics, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy.
    PurposeMowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. Read More

    Gene therapy for Mucopolysaccharidoses.
    Mol Genet Metab 2018 Feb 26;123(2):59-68. Epub 2017 Dec 26.
    Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States; Department of Pediatrics, Gifu University, Gifu, Japan; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, United States. Electronic address:
    Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders (LSDs) caused by a deficiency of lysosomal enzymes, leading to a wide range of various clinical symptoms depending upon the type of MPS or its severity. Enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), substrate reduction therapy (SRT), and various surgical procedures are currently available for patients with MPS. However, there is no curative treatment for this group of disorders. Read More

    Correction to: Impact of age at onset and newborn screening on outcome in organic acidurias.
    J Inherit Metab Dis 2017 Dec 12. Epub 2017 Dec 12.
    Department of General Pediatrics, Division of Neuropediatrics and Inherited Metabolic Diseases, University Children's Hospital, Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
    Due to an unfortunate error during the typesetting process, the collaborators were presented incorrectly. Read More

    In Niemann-Pick C1 mouse models, glial-only expression of the normal gene extends survival much further than do changes in genetic background or treatment with hydroxypropyl-beta-cyclodextrin.
    Gene 2018 Feb 6;643:117-123. Epub 2017 Dec 6.
    Department of Pediatrics, University of Arizona College of Medicine, Tucson, AZ 85724-5073, United States. Electronic address:
    The Npc1allele of Npc1 provides a mouse model for Niemann-Pick disease type C1 (NPC1), a genetic disease known to have a widely variable phenotype. The transfer of the Npc1mutation from the C57BL/6J inbred strain to the BALB/cJ inbred strain increased the mean lifespan from 117.8days to 153. Read More

    Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes Zellweger Spectrum Disorder.
    Am J Hum Genet 2017 Dec;101(6):965-976
    Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, the Netherlands. Electronic address:
    Zellweger spectrum disorders (ZSDs) are autosomal-recessive disorders that are caused by defects in peroxisome biogenesis due to bi-allelic mutations in any of 13 different PEX genes. Here, we identified seven unrelated individuals affected with an apparent dominant ZSD in whom a heterozygous mutant PEX6 allele (c.2578C>T [p. Read More

    Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.
    World J Gastroenterol 2017 Nov;23(44):7930-7938
    School of Medicine University of Belgrade, Belgrade 11000, Serbia.
    The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. Read More

    Audit of Organic Acidurias from a Single Centre: Clinical and Metabolic Profile at Presentation with Long Term Outcome.
    J Clin Diagn Res 2017 Sep 1;11(9):SC11-SC14. Epub 2017 Sep 1.
    Professor, Department of Paediatrics, K S Hegde Medical Academy, NITTE University, Mangalore, Karnataka, India.
    Introduction: Organic Acidurias (OA) accounts between 10% and 40% of confirmed Inborn Errors of Metabolism (IEM) in India. With prompt recognition and management, better survival but adverse neurodevelopmental outcome is reported.

    Aim: To study the clinical and metabolic presentation, management with immediate and long term outcome of symptomatic children with confirmed OA. Read More

    Progressive deafness-dystonia due to SERAC1 mutations: A study of 67 cases.
    Ann Neurol 2017 Dec;82(6):1004-1015
    Institute of Human Genetics, Technische UniversitätMünchen, Munich, Germany.
    Objective: 3-Methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome (MEGDHEL) syndrome is caused by biallelic variants in SERAC1.

    Methods: This multicenter study addressed the course of disease for each organ system. Metabolic, neuroradiological, and genetic findings are reported. Read More

    Novel mutation in the human HPRT1 gene and the Lesch-Nyhan disease.
    Nucleosides Nucleotides Nucleic Acids 2017 Nov 29;36(11):704-711. Epub 2017 Nov 29.
    b Department of Pediatrics, School of Medicine , University of California, San Diego , CA , USA.
    Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report a novel point mutation that led to HGprt-related neurological dysfunction (HND) in a family in which there was a missense mutation in exon 6 of the coding region of the HPRT1 gene: g.34938G>T, c. Read More

    Pompe disease in Austria: clinical, genetic and epidemiological aspects.
    J Neurol 2018 Jan 27;265(1):159-164. Epub 2017 Nov 27.
    Department of Neurology, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
    In this study, we performed a survey of infantile and late-onset Pompe disease (IOPD and LOPD) in Austria. Paediatric and neuromuscular centres were contacted to provide a set of anonymized clinical and genetic data of patients with IOPD and LOPD. The number of patients receiving enzyme replacement therapy (ERT) was obtained from the pharmaceutical company providing alglucosidase alfa. Read More

    The Role of Genetic Counseling in Pompe Disease After Patients Are Identified Through Newborn Screening.
    Pediatrics 2017 Jul;140(Suppl 1):S46-S50
    Department of Medical Genetics and Genomic Medicine, Saint Peter's University Hospital, New Brunswick, New Jersey
    An important part of the coordinated care by experienced health care teams for all Pompe disease patients, whether diagnosed through newborn screening (NBS), clinical diagnosis, or prenatal diagnosis, is genetic counseling. Genetic counseling helps families better understand medical recommendations and options presented by the patient's health care team so they can make informed decisions. In addition to providing important information about the inheritance and genetic risks, genetic counseling also provides information about Pompe disease and available treatments and resources and should be offered to families with an affected child and all adults diagnosed with Pompe disease. Read More

    Management of Confirmed Newborn-Screened Patients With Pompe Disease Across the Disease Spectrum.
    Pediatrics 2017 Jul;140(Suppl 1):S24-S45
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
    After a Pompe disease diagnosis is confirmed in infants identified through newborn screening (NBS), when and if to start treatment with enzyme replacement therapy (ERT) with alglucosidase alfa must be determined. In classic infantile-onset Pompe disease, ERT should start as soon as possible. Once started, regular, routine follow-up is necessary to monitor for treatment effects, disease progression, and adverse effects. Read More

    The Initial Evaluation of Patients After Positive Newborn Screening: Recommended Algorithms Leading to a Confirmed Diagnosis of Pompe Disease.
    Pediatrics 2017 Jul;140(Suppl 1):S14-S23
    Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
    Newborn screening (NBS) for Pompe disease is done through analysis of acid α-glucosidase (GAA) activity in dried blood spots. When GAA levels are below established cutoff values, then second-tier testing is required to confirm or refute a diagnosis of Pompe disease. This article in the "Newborn Screening, Diagnosis, and Treatment for Pompe Disease" guidance supplement provides recommendations for confirmatory testing after a positive NBS result indicative of Pompe disease is obtained. Read More

    Newborn Screening for Pompe Disease.
    Pediatrics 2017 Jul;140(Suppl 1):S4-S13
    Medical Genetics Service, Hospital de Clinicas de Porto Alegre (HCPA) and Department of Genetics, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
    Started in 1963 by Robert Guthrie, newborn screening (NBS) is considered to be one of the great public health achievements. Its original goal was to screen newborns for conditions that could benefit from presymptomatic treatment, thereby reducing associated morbidity and mortality. With advances in technology, the number of disorders included in NBS programs increased. Read More

    Age of heart disease presentation and dysmorphic nuclei in patients with LMNA mutations.
    PLoS One 2017 17;12(11):e0188256. Epub 2017 Nov 17.
    Departments of Biomedical Engineering, University of California, Irvine, CA, United States of America.
    Nuclear shape defects are a distinguishing characteristic in laminopathies, cancers, and other pathologies. Correlating these defects to the symptoms, mechanisms, and progression of disease requires unbiased, quantitative, and high-throughput means of quantifying nuclear morphology. To accomplish this, we developed a method of automatically segmenting fluorescently stained nuclei in 2D microscopy images and then classifying them as normal or dysmorphic based on three geometric features of the nucleus using a package of Matlab codes. Read More

    A multicenter, open-label, phase III study of Abcertin in Gaucher disease.
    Medicine (Baltimore) 2017 Nov;96(45):e8492
    aDepartment of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea bPaediatric GIT Unit, Mansoura University Children's Hospital cAbou El Reesh Children's Hospital, Cairo University, Egypt dMedical Genetics Center, Asan Medical Center eAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea fBiochemical Genetics Department, National Research Centre, Cairo, Egypt gISU ABXIS Co., Ltd, Seongnam, Korea.
    Background: Gaucher disease (GD) is caused by a deficiency in the lysosomal enzyme glucocerebrosidase. Enzyme replacement therapy (ERT) is recommended for clinical improvement.

    Methods: The efficacy and safety of a new imiglucerase, Abcertin, were assessed in 7 Egyptian patients with treatment-naïve type 1 GD. Read More

    Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes.
    Nat Commun 2017 Nov 10;8(1):1418. Epub 2017 Nov 10.
    Vaccine and Gene Therapy Institute, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR, 97006, USA.
    Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs. Read More

    Long-term benefit of enzyme replacement therapy in Pompe disease: A 5-year prospective study.
    Neurology 2017 Dec 8;89(23):2365-2373. Epub 2017 Nov 8.
    From the Erasmus MC University Medical Center (E.K., S.C.A.W., J.M.d.V., E.B., P.A.v.D., N.A.M.E.v.d.B.), Center for Lysosomal and Metabolic Diseases, Department of Neurology; Erasmus MC University Medical Center-Sophia Children's Hospital (M.E.K., J.C.v.d.M., A.T.v.d.P.), Center for Lysosomal and Metabolic Diseases, Department of Pediatrics; Erasmus MC University Medical Center (M.M.F.), Center for Lysosomal and Metabolic Diseases, Department of Rehabilitation Medicine and Physical Therapy; and Erasmus MC University Medical Center (D.R.), Department of Biostatistics, Rotterdam, the Netherlands.
    Objective: To determine the effect of enzyme replacement therapy (ERT) after 5 years and to identify predictors for a favorable response because few data are available on the long-term efficacy of ERT in Pompe disease.

    Methods: We included 102 adult patients with Pompe disease in a nationwide, prospective cohort study. We assessed muscle strength (manual muscle testing with Medical Research Council [MRC] grading, handheld dynamometry [HHD]), muscle function (6-minute walk test, Quick Motor Function Test), daily life activities (Rasch-Built Pompe-Specific Activity [R-PAct] Scale), and pulmonary function (forced vital capacity [FVC] in upright and supine positions, maximum inspiratory and expiratory pressures) at 3- to 6-month intervals before and after the start of ERT. Read More

    N-Butyl-l-deoxynojirimycin (l-NBDNJ): Synthesis of an Allosteric Enhancer of α-Glucosidase Activity for the Treatment of Pompe Disease.
    J Med Chem 2017 Dec 22;60(23):9462-9469. Epub 2017 Nov 22.
    Department of Chemical Sciences, Università degli Studi di Napoli Federico II , via Cintia, 80126 Napoli, Italy.
    The highly stereocontrolled de novo synthesis of l-NBDNJ (the unnatural enantiomer of the iminosugar drug Miglustat) and a preliminary evaluation of its chaperoning potential are herein reported. l-NBDNJ is able to enhance lysosomal α-glucosidase levels in Pompe disease fibroblasts, either when administered singularly or when coincubated with the recombinant human α-glucosidase. In addition, differently from its d-enantiomer, l-NBDNJ does not act as a glycosidase inhibitor. Read More

    Loss of β Epithelial Sodium Channel Function in Meibomian Glands Produces Pseudohypoaldosteronism 1-Like Ocular Disease in Mice.
    Am J Pathol 2018 01 26;188(1):95-110. Epub 2017 Oct 26.
    Marsico Lung Institute/University of North Carolina Cystic Fibrosis Research Center, School of Medicine, Chapel Hill, North Carolina. Electronic address:
    Human subjects with pseudohypoaldosteronism-1 because of loss-of-function mutations in epithelial sodium channel (ENaC) subunits exhibit meibomian gland (MG) dysfunction. A conditional βENaC MG knockout (KO) mouse model was generated to elucidate the pathogenesis of absent ENaC function in the MG and associated ocular surface disease. βENaC MG KO mice exhibited a striking age-dependent, female-predominant MG dysfunction phenotype, with white toothpaste-like secretions observed obstructing MG orifices at 7 weeks of age. Read More

    Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems.
    Annu Rev Pathol 2018 Jan 3;13:163-191. Epub 2017 Nov 3.
    Department of Pediatrics, Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA; email:
    Multisystem metabolic disorders caused by defects in oxidative phosphorylation (OXPHOS) are severe, often lethal, conditions. Inborn errors of OXPHOS function are termed primary mitochondrial disorders (PMDs), and the use of nutritional interventions is routine in their supportive management. However, detailed mechanistic understanding and evidence for efficacy and safety of these interventions are limited. Read More

    Muscle ultrasound: A useful tool in newborn screening for infantile onset pompe disease.
    Medicine (Baltimore) 2017 Nov;96(44):e8415
    aDepartment of Radiology bDepartment of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
    Our study aimed to evaluate the utility of muscle ultrasound in newborn screening of infantile-onset Pompe disease (IOPD) and to establish a system of severity grading. We retrospectively selected 35 patients with initial low acid alpha-glucosidase (GAA) activity and collected data including muscle ultrasound features, GAA gene mutation, activity/performance, and pathological and laboratory findings. The echogenicity of 6 muscles (the bilateral vastus intermedius, rectus femoris, and sartorius muscles) was compared to that of epimysium on ultrasound and rated either 1 (normal), 2 (mildly increased), or 3 (obviously increased). Read More

    Hematopoietic stem cell transplantation in Niemann-Pick disease type B monitored by chitotriosidase activity.
    Pediatr Blood Cancer 2018 Feb 1;65(2). Epub 2017 Nov 1.
    Paediatric Onco-Haematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital, Torino, Italy.
    Here, we report a patient with Niemann-Pick disease type B, with early severe onset of disease and pulmonary involvement, treated with hematopoietic stem cell transplant (HSCT) from a bone marrow matched unrelated donor. We confirm that HSCT is feasible and potentially beneficial for patients with severe phenotype. Noteworthy, we discussed the potential usefulness of the activity of peripheral chitotriosidase for the longitudinal evaluation of HSCT success and effectiveness. Read More

    Growth and Final Height Among Children With Phenylketonuria.
    Pediatrics 2017 Nov;140(5)
    Center for Pediatric Research Leipzig, Department of Women and Child Health, Hospital for Children and Adolescents, University Hospitals,
    Background And Objectives: Growth is an important criterion to evaluate health in childhood and adolescence, especially in patients depending on special dietary treatment. Phenylketonuria (PKU) is the most common inherited disease of amino acid metabolism. Patients with PKU depend on a special phenylalanine-restricted diet, low in natural protein. Read More

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