Search our Database of Scientific Publications and Authors

I’m looking for a

    11831 results match your criteria Pediatrics Inborn Errors of Metabolism

    1 OF 237

    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

    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

    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

    Split-graft liver transplantation from an adult donor with an unrecognized UCD to a pediatric and adult recipient.
    Pediatr Transplant 2017 Oct 16. Epub 2017 Oct 16.
    Department of Gastroenterology and Hepatology, The Children's Hospital at Westmead, Westmead, NSW, Australia.
    We report the outcomes of an adult and pediatric split liver transplant from an adult male donor who died due to an unrecognized UCD, OTC deficiency. Recognizing inborn errors of metabolism can be challenging, especially in adult centers where such disorders are rarely encountered. Shortage of donors for liver transplantation has led to procedures to maximize donor utilization, such as split and live donor grafts. Read More

    Oncometabolites: A New Paradigm for Oncology, Metabolism, and the Clinical Laboratory.
    Clin Chem 2017 Oct 16. Epub 2017 Oct 16.
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX;
    Background: Pediatric clinical laboratories commonly measure tricarboxylic acid cycle intermediates for screening, diagnosis, and monitoring of specific inborn errors of metabolism, such as organic acidurias. In the past decade, the same tricarboxylic acid cycle metabolites have been implicated and studied in cancer. The accumulation of these metabolites in certain cancers not only serves as a biomarker but also directly contributes to cellular transformation, therefore earning them the designation of oncometabolites. Read More

    Dietary practices in propionic acidemia: A European survey.
    Mol Genet Metab Rep 2017 Dec 3;13:83-89. Epub 2017 Oct 3.
    Birmingham Women's and Children's Hospital, Birmingham, UK.
    Background: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance.

    Aim: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines.

    Methods: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. Read More

    The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice.
    PLoS One 2017 5;12(10):e0185704. Epub 2017 Oct 5.
    Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.
    Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Read More

    Urinary metabolic phenotyping of mucopolysaccharidosis type I combining untargeted and targeted strategies with data modeling.
    Clin Chim Acta 2017 Oct 2;475:7-14. Epub 2017 Oct 2.
    Department of Metabolic Biochemistry, Rouen University Hospital, Rouen 76000, France; Normandie Univ, UNIROUEN, CHU Rouen, INSERM U1245, 76000 Rouen, France. Electronic address:
    Background: Application of metabolic phenotyping could expand the pathophysiological knowledge of mucopolysaccharidoses (MPS) and may reveal the comprehensive metabolic impairments in MPS. However, few studies applied this approach to MPS.

    Methods: We applied targeted and untargeted metabolic profiling in urine samples obtained from a French cohort comprising 19 MPS I and 15 MPS I treated patients along with 66 controls. Read More

    A high rate of novel CYP11B1 mutations in Saudi Arabia.
    J Steroid Biochem Mol Biol 2017 Nov 28;174:217-224. Epub 2017 Sep 28.
    Department of Pediatrics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
    Despite ethnic variation, 11 β-hydroxylase deficiency (11β-OHD) has generally been considered the second most common subtype of congenital adrenal hyperplasia (CAH). We report a high rate of novel mutations in this gene (CYP11B1) in patients from Saudi Arabia. We studied 16 patients with 11β-OHD from 8 unrelated families. Read More

    Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet.
    PLoS One 2017 29;12(9):e0184022. Epub 2017 Sep 29.
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, United States of America.
    Global metabolomic profiling offers novel opportunities for the discovery of biomarkers and for the elucidation of pathogenic mechanisms that might lead to the development of novel therapies. GLUT1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism due to reduced function of glucose transporter type 1. Clinical presentation of GLUT1-DS is heterogeneous and the disorder mirrors patients with epilepsy, movement disorders, or any paroxysmal events or unexplained neurological manifestation triggered by exercise or fasting. Read More

    Metabolic pathways at the crossroads of diabetes and inborn errors.
    J Inherit Metab Dis 2017 Sep 26. Epub 2017 Sep 26.
    Department of Pediatrics, School of Medicine, University of Pittsburgh, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
    Research over the past two decades has led to advances in our understanding of the genetic and metabolic factors that underlie the pathogenesis of type 2 diabetes mellitus (T2DM). While T2DM is defined by its hallmark metabolic symptoms, the genetic risk factors for T2DM are more immune-related than metabolism-related, and the observed metabolic disease may be secondary to chronic inflammation. Regardless, these metabolic changes are not benign, as the accumulation of some metabolic intermediates serves to further drive the inflammation and cell stress, eventually leading to insulin resistance and ultimately to T2DM. Read More

    Presumptive brain influx of large neutral amino acids and the effect of phenylalanine supplementation in patients with Tyrosinemia type 1.
    PLoS One 2017 26;12(9):e0185342. Epub 2017 Sep 26.
    Department of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
    Introduction: Hereditary Tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a defect in the tyrosine degradation pathway. Current treatment consists of 2-(2-nitro-4-trifluoromethylbenoyl)-1,3-cyclohexanedione (NTBC) and a tyrosine and phenylalanine restricted diet. Recently, neuropsychological deficits have been seen in HT1 patients. Read More

    Potential Role of Genomic Sequencing in the Early Diagnosis of Treatable Genetic Conditions.
    J Pediatr 2017 Oct;189:222-226.e1
    Division of Medical Genetics, Department of Pediatrics, University of California San Francisco, San Francisco, CA; Institute for Human Genetics, Benioff Children's Hospital San Francisco, University of California San Francisco, San Francisco, CA. Electronic address:
    We present cases of 3 children diagnosed with the same genetic condition, Gitelman syndrome, at different stages using various genetic methods: panel testing, targeted single gene sequencing, and exome sequencing. We discuss the advantages and disadvantages of each method and review the potential of genomic sequencing for early disease detection. Read More

    Plasma fibroblast growth factor-21 levels in patients with inborn errors of metabolism.
    Mol Genet Metab Rep 2017 Dec 4;13:52-54. Epub 2017 Sep 4.
    Children's National Health System, Division of Genetics & Metabolism, Washington, DC, United States.
    Fibroblast growth factor-21 (FGF21) levels are elevated in patients with primary mitochondrial disorders but have not been studied in patients with inborn errors of metabolism (IEM) known to have secondary mitochondrial dysfunction. We measured plasma FGF21 by ELISA in patients with and without IEM. FGF21 levels were higher in patients with IEM compared to without IEM (370 pg/dL vs. Read More

    Massive parallel sequencing as a new diagnostic approach for phenylketonuria and tetrahydrobiopterin-deficiency in Thailand.
    BMC Med Genet 2017 Sep 16;18(1):102. Epub 2017 Sep 16.
    Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
    Background: Hyperphenylalaninemia (HPA) can be classified into phenylketonuria (PKU) which is caused by mutations in the phenylalanine hydroxylase (PAH) gene, and BH4 deficiency caused by alterations in genes involved in tetrahydrobiopterin (BH4) biosynthesis pathway. Dietary restriction of phenylalanine is considered to be the main treatment of PKU to prevent irreversible intellectual disability. However, the same dietary intervention in BH4 deficiency patients is not as effective, as BH4 is also a cofactor in many neurotransmitter syntheses. Read More

    Simultaneous determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid in dried blood spots: Second-tier LC-MS/MS assay for newborn screening of propionic acidemia, methylmalonic acidemias and combined remethylation disorders.
    PLoS One 2017 15;12(9):e0184897. Epub 2017 Sep 15.
    Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany.
    Background And Aims: Increased propionylcarnitine levels in newborn screening are indicative for a group of potentially severe disorders including propionic acidemia (PA), methylmalonic acidemias and combined remethylation disorders (MMACBL). This alteration is relatively non-specific, resulting in the necessity of confirmation and differential diagnosis in subsequent tests. Thus, we aimed to develop a multiplex approach for concurrent determination of 3-hydroxypropionic acid, methylmalonic acid and methylcitric acid from the same dried blood spot (DBS) as in primary screening (second-tier test). Read More

    Cardiac Manifestations in Children with Inborn Errors of Metabolism.
    Indian Pediatr 2017 Aug;54(8):667-673
    From 4th Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece. Correspondence to: Dr Maria Gogou, Dimitriou Nika 44, 60 100, Katerini, Greece.
    Need And Purpose: Cardiac involvement is a part of many inborn errors of metabolism, but has not been systematically studied. This review focuses on studies describing cardiac manifestations of inborn errors of metabolism in childhood.

    Methods: Two independent reviewers searched the topic using PubMed database. Read More

    mTORC1 hyperactivation arrests bone growth in lysosomal storage disorders by suppressing autophagy.
    J Clin Invest 2017 Oct 5;127(10):3717-3729. Epub 2017 Sep 5.
    Telethon Institute of Genetics and Medicine (TIGEM), and.
    The mammalian target of rapamycin complex 1 (mTORC1) kinase promotes cell growth by activating biosynthetic pathways and suppressing catabolic pathways, particularly that of macroautophagy. A prerequisite for mTORC1 activation is its translocation to the lysosomal surface. Deregulation of mTORC1 has been associated with the pathogenesis of several diseases, but its role in skeletal disorders is largely unknown. Read More

    Expanded newborn metabolic screening programme in Hong Kong: a three-year journey.
    Hong Kong Med J 2017 Oct 1;23(5):489-96. Epub 2017 Sep 1.
    Centre of Inborn Errors of Metabolism, The Chinese University of Hong Kong, Shatin, Hong Kong.
    Introduction: No universal expanded newborn screening service for inborn errors of metabolism is available in Hong Kong despite its long history in developed western countries and rapid development in neighbouring Asian countries. To increase the local awareness and preparedness, the Centre of Inborn Errors of Metabolism of the Chinese University of Hong Kong started a private inborn errors of metabolism screening programme in July 2013. This study aimed to describe the results and implementation of this screening programme. Read More

    Efficacy and safety of intravenous laronidase for mucopolysaccharidosis type I: A systematic review and meta-analysis.
    PLoS One 2017 31;12(8):e0184065. Epub 2017 Aug 31.
    Postgraduate Program in Genetics Applied to Medicine, Department of Pediatrics, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
    Objective: To evaluate the efficacy and safety of IV laronidase for MPS I.

    Methods: A systematic literature review was performed by searching the ClinicalTrials.gov, MEDLINE/PubMed, EMBASE, LILACS, and Cochrane Library databases, limited to clinical trials published until December 31, 2016. Read More

    Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association.
    Circulation 2017 Sep 24;136(13):e200-e231. Epub 2017 Aug 24.
    For many neuromuscular diseases (NMDs), cardiac disease represents a major cause of morbidity and mortality. The management of cardiac disease in NMDs is made challenging by the broad clinical heterogeneity that exists among many NMDs and by limited knowledge about disease-specific cardiovascular pathogenesis and course-modifying interventions. The overlay of compromise in peripheral muscle function and other organ systems, such as the lungs, also makes the simple application of endorsed adult or pediatric heart failure guidelines to the NMD population problematic. Read More

    Efficacy of Rosuvastatin in Children With Homozygous Familial Hypercholesterolemia and Association With Underlying Genetic Mutations.
    J Am Coll Cardiol 2017 Aug;70(9):1162-1170
    Department of Paediatrics and Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
    Background: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children.

    Objectives: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations. Read More

    Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy.
    Neurology 2017 Sep 23;89(12):1274-1282. Epub 2017 Aug 23.
    From the Department of Neuroradiology (T.G., P.B., M.P., M.K., J.K., S.H., M.B.), Neurological University Clinic, Heidelberg University Hospital; Department of Radiology (P.B.), German Cancer Research Institute, Heidelberg; Department of Neuroradiology (M.P.), Würzburg University Hospital; Department of Pediatrics (A.K., N.M.), University Medical Center Hamburg-Eppendorf; and Department of Neurology (V.-F.M.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Objective: To evaluate functional and morphometric magnetic resonance neurography of the dorsal root ganglion and peripheral nerve segments in patients with Fabry painful neuropathy.

    Methods: In this prospective study, the lumbosacral dorsal root ganglia and proximal peripheral nerve segments of the lower extremity were examined in 11 male patients with Fabry disease by a standardized 3T magnetic resonance neurography protocol. Volumes of L3 to S2 dorsal root ganglia, perfusion parameters of L5-S1 dorsal root ganglia and the spinal nerve L5, and the cross-sectional area of the proximal sciatic nerve were compared to healthy controls. Read More

    A novel image-based high-throughput screening assay discovers therapeutic candidates for adult polyglucosan body disease.
    Biochem J 2017 Sep 28;474(20):3403-3420. Epub 2017 Sep 28.
    Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
    Glycogen storage disorders (GSDs) are caused by excessive accumulation of glycogen. Some GSDs [adult polyglucosan (PG) body disease (APBD), and Tarui and Lafora diseases] are caused by intracellular accumulation of insoluble inclusions, called PG bodies (PBs), which are chiefly composed of malconstructed glycogen. We developed an APBD patient skin fibroblast cell-based assay for PB identification, where the bodies are identified as amylase-resistant periodic acid-Schiff's-stained structures, and quantified. Read More

    Kernicterus in a boy with ornithine transcarbamylase deficiency: A case report.
    Neuropathology 2017 Aug 16. Epub 2017 Aug 16.
    Inborn Errors of Metabolism and Screening Laboratory, National Institute of Pediatrics, Mexico City, Mexico State, Mexico.
    Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle defect associated with severe and usually fatal hyperammonemia. This study describes a patient with early onset lethal OTCD due to a known pathogenic variant (c.298+1G>A), as well as the novel autopsy finding of kernicterus with relatively low blood concentration of unconjugated bilirubin (UCB) (11. Read More

    Circulating miR-200c is up-regulated in paediatric patients with familial hypercholesterolaemia and correlates with miR-33a/b levels: implication of a ZEB1-dependent mechanism.
    Clin Sci (Lond) 2017 Sep 8;131(18):2397-2408. Epub 2017 Sep 8.
    Istituto Dermopatico dell'Immacolata-IRCCS, FLMM, Vascular Pathology Laboratory, Via dei Monti di Creta 104, Rome 00167, Italy
    Hypercholesterolaemia provokes reactive oxygen species (ROS) increase and is a major risk factor for cardiovascular disease (CVD) development. We previously showed that circulating miR-33a/b expression levels were up-regulated in children with familial hypercholesterolaemia (FH). miR-33a/b control cholesterol homoeostasis and recently miR-33b has been demonstrated to directly target the transcription factor zinc finger E-box-binding homeobox 1 (ZEB1). Read More

    Inborn errors in RNA polymerase III underlie severe varicella zoster virus infections.
    J Clin Invest 2017 Sep 7;127(9):3543-3556. Epub 2017 Aug 7.
    Department of Infectious Diseases, Aarhus University Hospital Skejby, Aarhus, Denmark.
    Varicella zoster virus (VZV) typically causes chickenpox upon primary infection. In rare cases, VZV can give rise to life-threatening disease in otherwise healthy people, but the immunological basis for this remains unexplained. We report 4 cases of acute severe VZV infection affecting the central nervous system or the lungs in unrelated, otherwise healthy children who are heterozygous for rare missense mutations in POLR3A (one patient), POLR3C (one patient), or both (two patients). Read More

    Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome.
    Am J Hum Genet 2017 Aug;101(2):239-254
    Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC 3052, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC 3052, Australia; Victorian Clinical Genetic Services, Royal Children's Hospital, Melbourne, VIC 3052, Australia. Electronic address:
    The synthesis of all 13 mitochondrial DNA (mtDNA)-encoded protein subunits of the human oxidative phosphorylation (OXPHOS) system is carried out by mitochondrial ribosomes (mitoribosomes). Defects in the stability of mitoribosomal proteins or mitoribosome assembly impair mitochondrial protein translation, causing combined OXPHOS enzyme deficiency and clinical disease. Here we report four autosomal-recessive pathogenic mutations in the gene encoding the small mitoribosomal subunit protein, MRPS34, in six subjects from four unrelated families with Leigh syndrome and combined OXPHOS defects. Read More

    Serum Soluble Transferrin Receptor Concentrations Are Elevated in Congolese Children with Glucose-6-Phosphate Dehydrogenase Variants, but Not Sickle Cell Variants or α-Thalassemia.
    J Nutr 2017 Sep 2;147(9):1785-1794. Epub 2017 Aug 2.
    Food, Nutrition, and Health and
    Background: Anemia is common in Congolese children, and inherited blood disorders may be a contributing cause. The presence of sickle cell variants, X-linked glucose-6-phosphate dehydrogenase (G6PD) deficiency and α-thalassemia, has been previously reported. G6PD A- deficiency is characterized by the co-inheritance of G6PD 376 and 202 variants and is common in sub-Saharan Africa. Read More

    Outcomes after 18 months of eliglustat therapy in treatment-naïve adults with Gaucher disease type 1: The phase 3 ENGAGE trial.
    Am J Hematol 2017 Nov 3;92(11):1170-1176. Epub 2017 Oct 3.
    Rare Diseases Clinical Development, Sanofi Genzyme, Cambridge, MA, USA.
    Eliglustat, an oral substrate reduction therapy, is a first-line treatment for adults with Gaucher disease type 1 (GD1) who are poor, intermediate, or extensive CYP2D6 metabolizers (>90% of patients). In the primary analysis of the Phase 3 ENGAGE trial (NCT00891202), eliglustat treatment for 9 months resulted in significant reductions in spleen and liver volumes and increases in hemoglobin concentration and platelet count compared with placebo. We report 18-month outcomes of patients who entered the trial extension period, in which all patients received eliglustat. Read More

    Impairment of GABAergic system contributes to epileptogenesis in glutaric acidemia type I.
    Epilepsia 2017 Oct 1;58(10):1771-1781. Epub 2017 Aug 1.
    Postgraduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
    Objectives: Glutaric acidemia type I (GA-I) is an inherited neurometabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase (GCDH) and characterized by increased levels of glutaric, 3-OH-glutaric, and glutaconic acids in the brain parenchyma. The increment of these organic acids inhibits glutamate decarboxylase (GAD) and consequently lowers the γ-aminobutyric acid (GABA) synthesis. Untreated patients exhibit severe neurologic deficits during development, including epilepsy, especially following an acute encephalopathy outbreak. Read More

    Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase Deficiency.
    Pediatrics 2017 Jul;140(1)
    Division of Neonatology, Department of Pediatrics, University of Florida, Gainesville, Florida.
    We present a 6-week-old male infant with persistent hyperbilirubinemia, hypertriglyceridemia, elevated creatine kinase levels, and transaminitis since the second week of life. When he developed hyperkalemia, clinical suspicion was raised for adrenal insufficiency despite hemodynamic stability. A full endocrine workup revealed nearly absent adrenocorticotropic hormone. Read More

    Ophthalmologic Features of Progeria.
    Am J Ophthalmol 2017 Oct 27;182:126-132. Epub 2017 Jul 27.
    Department of Anesthesia, Boston Children's Hospital - Harvard Medical School, Boston, Massachusetts; Department of Pediatrics, Hasbro Children's Hospital - Warren Alpert Medical School of Brown University, Providence, Rhode Island.
    Purpose: To establish the natural history of ophthalmic characteristics in Progeria patients and to determine incidence of ocular manifestations.

    Design: Retrospective case series of patients with Progeria who were seen between 2007 and 2016.

    Methods: Setting: Tertiary-care academic center. Read More

    Measurement of Oncometabolites D-2-Hydroxyglutaric Acid and L-2-Hydroxyglutaric Acid.
    Methods Mol Biol 2017 ;1633:219-234
    Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
    We describe a liquid chromatography-tandem mass spectrometry assay for measurement of D-2-hydroxyglutaric acid and L-2-hydroxyglutaric acid. These metabolites are increased in specific inborn errors of metabolism and are now recognized as oncometabolites. The measurement of D-2-hydroxyglutarate in peripheral blood may be used as a biomarker for screening and follow-up of patients with IDH-mutated acute myeloid leukemia. Read More

    Knowledge base and mini-expert platform for the diagnosis of inborn errors of metabolism.
    Genet Med 2017 Jul 20. Epub 2017 Jul 20.
    Division of Metabolism, University Children's Hospital, Zurich, Switzerland.
    PurposeRecognizing individuals with inherited diseases can be difficult because signs and symptoms often overlap those of common medical conditions. Focusing on inborn errors of metabolism (IEMs), we present a method that brings the knowledge of highly specialized experts to professionals involved in early diagnoses. We introduce IEMbase, an online expert-curated IEM knowledge base combined with a prototype diagnosis support (mini-expert) system. Read More

    Clinical characteristics and mutation spectrum of GLA in Korean patients with Fabry disease by a nationwide survey: Underdiagnosis of late-onset phenotype.
    Medicine (Baltimore) 2017 Jul;96(29):e7387
    aDepartment of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine bAsan Institute for Life Sciences cMedical Genetics Center, Asan Medical Center Children's Hospital, Seoul dDepartment of Pediatrics, Pusan National University Children's Hospital eDepartment of Neurology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan fDepartment of Pediatrics, Seoul National University Children's Hospital, Seoul gDepartment of Medical Genetics, Ajou University Hospital, Ajou University School of Medicine, Suwon hDepartment of Pediatrics, College of Medicine, Soonchunhyang University, Bucheon Hospital, Bucheon iDepartment of Pediatrics, College of Medicine, Soonchunhyang University, Seoul Hospital, Seoul jDepartment of Pediatrics, Chonnam National University Hwasun Hospital, Hwasun kDepartment of Pediatrics, Chungnam National University Hospital, Daejeon lDepartment of Cardiology, Bucheon Sejong Hospital, Bucheon mDepartment of Cardiology, Kyung Hee University Hospital nDepartment of Cardiology, Yonsei University Severance Hospital oDepartment of Nephrology, Chung-Ang University Hospital pDepartment of Cardiology, Eulji University Hospital, Seoul qDepartment of Nephrology, Kyungpook National University Hospital, Daegu rDivision of Nephrology, Department of Internal Medicine, Dankook University Hospital, Dankook University, College of Medicine, Cheonan sDepartment of Cardiology, Inje University Busan Paik Hospital, Busan, Republic of Korea.
    Fabry disease is a rare X-linked lysosomal storage disorder caused by an α-galactosidase A deficiency. The progressive accumulation of globotriaosylceramide (GL-3) results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. This study investigated the phenotypic and molecular spectra of GLA mutations in Korean patients with Fabry disease using a nationwide survey. Read More

    Intracerebral gene therapy in children with mucopolysaccharidosis type IIIB syndrome: an uncontrolled phase 1/2 clinical trial.
    Lancet Neurol 2017 Sep 14;16(9):712-720. Epub 2017 Jul 14.
    Department of Neuroscience, Biotherapy and Neurodegenerative Diseases Unit, INSERM U1115, Institut Pasteur, Paris, France.
    Background: Mucopolysaccharidosis type IIIB syndrome (also known as Sanfilippo type B syndrome) is a lysosomal storage disease resulting in progressive deterioration of cognitive acquisition after age 2-4 years. No treatment is available for the neurological manifestations of the disease. We sought to assess the safety and efficacy of a novel intracerebral gene therapy. Read More

    Brain carnitine deficiency causes nonsyndromic autism with an extreme male bias: A hypothesis.
    Bioessays 2017 Aug 13;39(8). Epub 2017 Jul 13.
    Departments of Molecular and Human Genetics and Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
    Could 10-20% of autism be prevented? We hypothesize that nonsyndromic or "essential" autism involves extreme male bias in infants who are genetically normal, but they develop deficiency of carnitine and perhaps other nutrients in the brain causing autism that may be amenable to early reversal and prevention. That brain carnitine deficiency might cause autism is suggested by reports of severe carnitine deficiency in autism and by evidence that TMLHE deficiency - a defect in carnitine biosynthesis - is a risk factor for autism. A gene on the X chromosome (SLC6A14) likely escapes random X-inactivation (a mixed epigenetic and genetic regulation) and could limit carnitine transport across the blood-brain barrier in boys compared to girls. Read More

    Increased urinary prostaglandin E2 metabolite: A potential therapeutic target of Gitelman syndrome.
    PLoS One 2017 10;12(7):e0180811. Epub 2017 Jul 10.
    Department of Nephrology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
    Background: Gitelman syndrome (GS), an inherited autosomal recessive salt-losing renal tubulopathy caused by mutations in SLC12A3 gene, has been associated with normal prostaglandin E2 (PGE2) levels since 1995 by a study involving 11 clinically diagnosed patients. However, it is difficult to explain why cyclooxygenase-2 (COX2) inhibitors, which pharmacologically reduce PGE2 synthesis, are helpful to patients with GS, and few studies performed in the last 20 years have measured PGE2 levels. The relationships between the clinical manifestations and PGE2 levels were never thoroughly analyzed. Read More

    [Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene].
    Zhongguo Dang Dai Er Ke Za Zhi 2017 Jul;19(7):734-740
    Department of Pediatrics, First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
    Congenital bile acid synthesis defect type 2 (CBAS2) is an autosomal recessive disorder caused by biallelic mutations of AKR1D1 gene, which encodes the Δ4-3-oxo-steroid 5β-reductase. Cholestatic jaundice is the main clinical manifestation, accompanied by malabsorption of fat and fat-soluble vitamins. This paper reported the clinical and genetic features of a CBAS2 patient definitely diagnosed by AKR1D1 genetic analysis. Read More

    Wilson's disease and diagnostic conundrum in a low income country.
    Pan Afr Med J 2017 13;26:201. Epub 2017 Apr 13.
    Department of Pediatrics, ALL India Institute of Medical Sciences, Patna, Bihar, India.
    Wilson's disease is a well-known leading cause of chronic liver disease in children. However it may remain undiagnosed in a resource limited setting for a long period. We describe a six year male child diagnosed Wilson's disease with extreme elevation of liver enzymes which is not reported earlier. Read More

    A Newborn with an Alternative Porto-Caval Shunt.
    Pol J Radiol 2017 16;82:320-321. Epub 2017 Jun 16.
    Department of Radiology, Gazi University, Faculty of Medicine, Ankara, Turkey.
    Background: Absent ductus venosus (ADV) is a rare condition, but it should be known that this embryonic anomaly may be detected by fetal echocardiographic or newborn ultrasound examinations.

    Case Report: We present a baby with an ADV and an accompanying alternative porto-caval shunt between the right portal vein and inferior vena cava detected on postnatal ultrasound examination.

    Conclusions: Variations in the fetal umbilical or porto-systemic circulations should be detected by fetal or newborn ultrasound examinations and kept in mind before common interventions such as UV catheterizations. Read More

    Early Screening for Tetrahydrobiopterin Responsiveness in Phenylketonuria.
    Pediatrics 2017 Aug 5;140(2). Epub 2017 Jul 5.
    Department of Pediatrics, University of Torino, Torino, Italy.
    Since 2007, synthetic tetrahydrobiopterin (BH4) has been approved as a therapeutic option in BH4-responsive phenylketonuria (PKU) and since 2015 extended to infants younger than 4 years in Europe. The current definition of BH4 responsiveness relies on the observation of a 20% to 30% blood phenylalanine (Phe) decrease after BH4 administration, under nonstandardized conditions. By this definition, however, patients with the same genotype or even the same patients were alternatively reported as responsive or nonresponsive to the cofactor. Read More

    Inborn Errors of Metabolism and Epilepsy: Current Understanding, Diagnosis, and Treatment Approaches.
    Int J Mol Sci 2017 Jul 2;18(7). Epub 2017 Jul 2.
    Department of Pediatrics and Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Children's Hospital of Western Ontario and London Health Sciences Centre, London, ON N6A5W9, Canada.
    Inborn errors of metabolism (IEM) are a rare cause of epilepsy, but seizures and epilepsy are frequently encountered in patients with IEM. Since these disorders are related to inherited enzyme deficiencies with resulting effects on metabolic/biochemical pathways, the term "metabolic epilepsy" can be used to include these conditions. These epilepsies can present across the life span, and share features of refractoriness to anti-epileptic drugs, and are often associated with co-morbid developmental delay/regression, intellectual, and behavioral impairments. Read More

    Neonatal-onset carbamoyl phosphate synthetase I deficiency: A case report.
    Medicine (Baltimore) 2017 Jun;96(26):e7365
    aDepartment of Pediatrics, West China Second University Hospital bKey Laboratory of Obstetric & Gynaecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, Sichuan, China.
    Rationale: The carbamoyl phosphate synthetase I deficiency (CPS1D) was rare and hard to diagnose due to its atypical symptoms. Brain magnetic resonance imaging (MRI) was typically unavailable in other reports because most patients died before diagnosis was confirmed. Furthermore, it was found a new mutation that had not been described previously. Read More

    Amino acid synthesis deficiencies.
    J Inherit Metab Dis 2017 Jul 26;40(4):609-620. Epub 2017 Jun 26.
    Paediatrician for Inborn Errors of Metabolism, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
    In recent years the number of disorders known to affect amino acid synthesis has grown rapidly. Nor is it just the number of disorders that has increased: the associated clinical phenotypes have also expanded spectacularly, primarily due to the advances of next generation sequencing diagnostics. In contrast to the "classical" inborn errors of metabolism in catabolic pathways, in which elevated levels of metabolites are easily detected in body fluids, synthesis defects present with low values of metabolites or, confusingly, even completely normal levels of amino acids. Read More

    Successful pregnancy and delivery in a woman with propionic acidemia from the Amish community.
    Mol Genet Metab Rep 2016 Sep 2;8:4-7. Epub 2016 Jun 2.
    LaFarge Medical Clinic, LaFarge, WI, USA.
    Propionic acidemia (PA) is an inborn error of protein metabolism with a variable clinical presentation ranging from neonatal encephalopathy to seemingly asymptomatic individuals who present with cardiomyopathy or sudden death. PA is recognized in the Amish population, often with an early asymptomatic course and eventual cardiac complications. Thus, Amish women with PA may reach reproductive age without clinical sequelae, but are at increased risk for metabolic decompensation during pregnancy, delivery and postpartum period. Read More

    Temporal Signal Pattern Recognition in Mass Spectrometry: A Method for Rapid Identification and Accurate Quantification of Biomarkers for Inborn Errors of Metabolism with Quality Assurance.
    Anal Chem 2017 Aug 11;89(15):8112-8121. Epub 2017 Jul 11.
    Department of Chemistry and Chemical Biology, McMaster University , Hamilton L8S 4M1, Canada.
    Mass spectrometry (MS)-based metabolomic initiatives that use conventional separation techniques are limited by low sample throughput and complicated data processing that contribute to false discoveries. Herein, we introduce a new strategy for unambiguous identification and accurate quantification of biomarkers for inborn errors of metabolism (IEM) from dried blood spots (DBS) with quality assurance. A multiplexed separation platform based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) was developed to provide comparable sample throughput to flow injection analysis-tandem MS (FIA-MS/MS) but with greater selectivity as required for confirmatory testing and discovery-based metabolite profiling of volume-restricted biospecimens. Read More

    1 OF 237