Abstract
Original language | English |
---|---|
Pages (from-to) | 93-106 |
Number of pages | 14 |
Journal | Journal of Inherited Metabolic Disease |
Volume | 42 |
Issue number | 1 |
DOIs | |
Publication status | Published - 1 Jan 2019 |
Keywords
- Urea cycle Disorders
- diagnostic methods
- international registry and database
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In: Journal of Inherited Metabolic Disease, Vol. 42, No. 1, 01.01.2019, p. 93-106.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders—A successful strategy for clinical research of rare diseases
AU - Posset, Roland
AU - Garbade, Sven F.
AU - Boy, Nikolas
AU - Burlina, Alberto B.
AU - Dionisi-Vici, Carlo
AU - Dobbelaere, Dries
AU - Garcia-Cazorla, Angeles
AU - de Lonlay, Pascale
AU - Teles, Elisa Leão
AU - Vara, Roshni
AU - Mew, Nicholas Ah
AU - Batshaw, Mark L.
AU - Baumgartner, Matthias R.
AU - McCandless, Shawn E.
AU - Seminara, Jennifer
AU - Summar, Marshall
AU - Hoffmann, Georg F.
AU - Kölker, Stefan
AU - Burgard, Peter
AU - Berry, Susan A.
AU - Burrage, Lindsay
AU - Coughlin, Curtis
AU - Diaz, George A.
AU - Gallagher, Renata C.
AU - Gropman, Andrea
AU - Harding, Cary O.
AU - Lee, Brendan
AU - le Mons, Cynthia
AU - Lawrence Merritt, J.
AU - Nagamani, Sandesh C. S.
AU - Schulze, Andreas
AU - Stricker, Tamar
AU - Tuchman, Mendel
AU - Waisbren, Susan
AU - WeisfeldAdams, James
AU - Wong, Derek
AU - Yudkoff, Marc
AU - Arnoux, JeanBaptiste
AU - Barić, Ivo
AU - Bosch, Annet M.
AU - Chabrol, Brigitte
AU - Chakrapani, Anupam
AU - CortèsSaladefont, Elisenda
AU - Couce, Maria L.
AU - Eyskens, Francois
AU - de Laet, Corine
AU - de Meirleir, Linda
AU - Freisinger, Peter
AU - Gleich, Florian
AU - Additional Individual Contributors Of The Ucdc And The E-Imd Consortium
AU - Bosch, Annet M.
AU - Williams, Monique
AU - Zeman, J.
N1 - Funding Information: NICHD, O'Malley Family Foundation, Kettering Fund, Dietmar Hopp Foundation, Rothenberg Family Foundation, European Union, Kindness for Kids Foundation, Radiz, Association La vita è un dono Funding Information: The Urea Cycle Disorders Consortium (UCDC) was founded by the National Institutes of Health in 2003 in the United States as part of the Rare Diseases Clinical Research Network (http://www.rarediseasesnetwork.org/cms/UCDC). The European registry and network for Intoxication type Metabolic Diseases (E-IMD) was established in 2011 (http:// www.e-imd.org), funded by the European Union from 1st January 2011 to 30th April 2014 in the framework of the Health Programme 2008–2013 and later on by mixed funding sources (for details see the “Acknowledgements” section). Descriptions of the research networks have been published previously.1–3 The objective of both projects is to improve knowledge on the natural history, treatment and outcome of urea cycle disorders (UCDs) by collecting longitudinal data on clinical, biochemical and treatment parameters, to foster training for families and professionals, and to develop evidence-based recommendations for six enzymopathies, i.e. deficiencies of N-acetylglutamate synthase (NAGS-D; OMIM #237310), carbamyl phosphate synthetase 1 (CPS1-D; OMIM #237300), ornithine transcarbamylase (OTC-D; OMIM #311250), argininosuccinate synthetase (ASS-D; OMIM #215700), argininosuccinate lyase (ASL-D; OMIM #207900) and arginase 1 (ARG1-D; OMIM #207800), and two transporter defects, i.e. deficiencies of the citrin or aspartate/glutamate carrier (CITR-D; OMIM #603471 and #605814; UCDC only) and the mitochondrial ornithine transporter 1 causing hyperornithinemia–hyperammonemia– homocitrullinuria syndrome (HHH syndr.; OMIM #238970). The estimated cumulative prevalence of UCDs has been reported as 1 in 52,000−35,000 newborns.4–6 Based on large data samples, several UCDC and E-IMD research projects have been published previously.1,6–17 Funding Information: The UCDC longitudinal study has received funding from the National Institute for Child Health and Human Development (NICHD U54 HD061221), the O'Malley Family Foundation, the Kettering Fund, the Dietmar Hopp Foundation and the Rothenberg Family Foundation. Funding Information: The E-IMD patient registry has received funding from the European Union (E-IMD; EAHC no. December 1, 2010; coordinator: Stefan Kölker), in the framework of the Health Programme. After the end of the EU funding period, the E-IMD patient registry has been sustained by funding from the Kindness for Kids Foundation (Munich, Germany), the Kettering Foundation (Dayton, Ohio, USA), and the Dietmar Hopp Foundation (St. Leon-Rot, Germany). M. Baumgartner and J. Häberle (Zurich, Switzerland) are supported by radiz - Rare Disease Initiative Zurich, a clinical research priority programme of the University of Zurich. C. Dionisi-Vici (Rome, Italy) is supported by the association “La vita è un dono”. Funding Information: Oregon Health and Science University, Portland, Oregon, USA Brendan Lee Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, USA Cynthia Le Mons National Urea Cycle Disorders Foundation, Pasadena, California, USA J. Lawrence Merritt II University of Washington and Seattle Children’s Hospital, Seattle, Washington, USA Sandesh C. S. Nagamani Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, USA Andreas Schulze The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada Tamar Stricker University Children’s Hospital Zurich, Zurich, Switzerland Mendel Tuchman Children’s National Health System and The George Washington School of Medicine, Washington, District of Columbia, USA Susan Waisbren Harvard Medical School and Boston Children’s Hospital, Boston, Massachusetts, USA James Weisfeld-Adams Children’s Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado, USA Derek Wong David Geffen School of Medicine at UCLA, Los Angeles, California, USA Marc Yudkoff University of Pennsylvania School of Medicine and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA From the E-IMD Jean-Baptiste Arnoux Hôpital Necker-Enfants Malades, Assistance Publique-Hôpi-taux de Paris, Service de Maladies Métaboliques, Paris, France Ivo Barić University Hospital Center Zagreb and University of Zagreb, School of Medicine, Zagreb, Croatia Annet M. Bosch Academisch Medisch Centrum, Department of Pediatrics, Amsterdam, The Netherlands Brigitte Chabrol Centre de Référence des Maladies Héréditaires du Métabo-lisme, Service de Neurologie, Hôpital d’Enfants, CHU Timone, Marseille, France Anupam Chakrapani Metabolic Unit Great Ormond Street Hospital and Institute for Child Health, University College London, London, United Kingdom Elisenda Cortès-Saladelafont Hospital San Joan de Deu, Institut Pediàtric de Recerca. Ser-vicio de Neurologia and CIBERER, ISCIII, Barcelona, Spain Maria L. Couce Hospital Clinico Universitario de Santiago de Compostela, Metabolic Unit, Department of Pediatrics, Santiago de Com-postela, Spain Francois Eyskens Universitair Ziekenhuis Antwerpen, Antwerpen, Belgium Corine de Laet Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium Linda de Meirleir University Hospital Vrije Universiteit Brussel, Bruxelles, Belgium Peter Freisinger Klinik für Kinder-und Jugendmedizin, Klinikum am Stei-nenberg, Reutlingen, Germany Florian Gleich Centre for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Inherited Metabolic Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany Stephanie Grünewald Metabolic Unit Great Ormond Street Hospital and Institute for Child Health, University College London, London, United Kingdom Johannes Häberle University Children’s Hospital Zurich, Division of Metabolism and Children’s Research Centre, Steinwiesstraße 75, CH-8032 Zurich, Switzerland Wuh-Liang Hwu Department of Medical Genetics, National Taiwan University, Hospital, Taipei City, Taiwan Anil Jalan N.I.R.M.A.N., Om Rachna Society, Vashi, Navi Mumbai, Mumbai, India Daniela Karall Medical University of Innsbruck, Clinic for Pediatrics I, Inherited Metabolic Disorders, Innsbruck, Austria Martin Lindner University Children’s Hospital Frankfurt, Frankfurt, Germany Allan M. Lund Centre for Inherited Metabolic Diseases, Departments of Pediatrics and Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark Diego Martinelli Funding Information: Ospedale Pediatrico Bambino Gésu, U.O.C. Patologia Meta-bolica, Rome, Italy Elaine Murphy National Hospital for Neurology and Neurosurgery, Charles Dent Metabolic Unit, London, United Kingdom Chris Mühlhausen University Children’s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Giorgia Olivieri Ospedale Pediatrico Bambino Gésu, U.O.C. Patologia Meta-bolica, Rome, Italy Chris Ottolenghi Hôpital Necker-Enfants Malades, Assistance Publique-Hôpi-taux de Paris, Service de Maladies Métaboliques, Paris, France Esmeralda Rodrigues Unidade de Doenças Metabólicas, Serviço de Pediatria, Hospital de S. João, EPE, Porto, Portugal Laura Rubert Azienda Ospedaliera di Padova, U.O.C. Malattie Metabo-liche Ereditarie, Padova, Italy Adrijan Sarajlija Belgrade University, School of Medicine, Belgrade, Republic of Serbia Manuel Schiff Hôpital Robert Debré, APHP and Université Paris-Diderot, Reference Centre for Inborn Errors of Metabolism, Paris, France Etienne Sokal Cliniques Universitaires St Luc, Université Catholique de Louvain, Service Gastroentérologie and Hépatologie Pédia-trique, Bruxelles, Belgium Jolanta Sykut-Cegielska Dep Inborn Errors of Metabolism and Paediatrics, the Institute of Mother and Child, Warsaw, Poland John H. Walter Manchester Academic Health Science Centre, University of Manchester, Willink Biochemical Genetics Unit, Genetic Medicine, Manchester, United Kingdom Monique Williams Erasmus MC-Sophia Kinderziekenhuis, Erasmus Universi-teit Rotterdam, Rotterdam, The Netherlands Jiri Zeman Department of Paediatrics, First Faculty of Medicine and General Faculty Hospital, Prague, Czech Republic Funding Information: Stefan Kölker receives funding from Horizon Pharma Ireland Limited for the European Post-Authorization Registry for Ravicti (glycerol phenylbutyrate) oral liquid in partnership with the E-IMD (RRPE) (EU PAS Register no. EUPAS17267; http://www.encepp.eu). Georg F. Hoffmann, Peter Burgard and Stefan Kölker receive funding from the Dietmar Hopp Foundation (St. Leon-Rot, Germany) for coordinating the study “Newborn Screening and Metabolic Medicine 2020 (NBS2020)” including individuals with urea cycle disorders. The sponsors have in no way influenced the design, conductance, analysis and report of the present study. All other authors declare that they have no conflict of interest. Publisher Copyright: © 2018 SSIEM Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Background: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. Aims: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. Methods: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. Results: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (≤ 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. Conclusions: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies.
AB - Background: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. Aims: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. Methods: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. Results: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (≤ 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. Conclusions: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies.
KW - Urea cycle Disorders
KW - diagnostic methods
KW - international registry and database
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85061242211&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30740724
UR - http://www.scopus.com/inward/record.url?scp=85061242211&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jimd.12031
DO - https://doi.org/10.1002/jimd.12031
M3 - Article
C2 - 30740724
SN - 0141-8955
VL - 42
SP - 93
EP - 106
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 1
ER -