Roland Posset1, Sven F Garbade1, Nikolas Boy1, Alberto B Burlina2, Carlo Dionisi-Vici3, Dries Dobbelaere4, Angeles Garcia-Cazorla5, Pascale de Lonlay6, Elisa Leão Teles7, Roshni Vara8, Nicholas Ah Mew9, Mark L Batshaw9, Matthias R Baumgartner10, Shawn E McCandless11, Jennifer Seminara9, Marshall Summar12, Georg F Hoffmann1, Stefan Kölker1, Peter Burgard1. 1. Centre for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Inherited Metabolic Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 430 69120, Heidelberg, Germany. 2. Azienda Ospedaliera di Padova, U.O.C. Malattie Metaboliche Ereditarie, Padova, Italy. 3. Ospedale Pediatrico Bambino Gésu, U.O.C. Patologia Metabolica, Rome, Italy. 4. Centre de Référence Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte, Jeanne de Flandre Hospital, CHRU Lille, and RADEME EA 7364, Faculty of Medicine, University Lille 2 59037, Lille, France. 5. Hospital San Joan de Deu, Institut Pediàtric de Recerca, Servicio de Neurologia and CIBERER, ISCIII, Barcelona, Spain. 6. Service de Maladies Métaboliques, Hôpital Necker-Enfants Malades Assistance Publique-Hôpitaux de Paris, Paris, France. 7. Unidade de Doenças Metabólicas, Serviço de Pediatria, Hospital de S. João, EPE, Porto, Portugal. 8. Evelina Children's Hospital, St Thomas' Hospital, London, UK. 9. Children's Research Institute, Children's National Health System, 111 Michigan Ave. NW, Washington, District of Columbia 20010, USA. 10. Division of Metabolism and Children's Research Centre, University Children's Hospital Zurich, Steinwiesstraße 75, CH-8032 Zurich, Zurich, Switzerland. 11. Section of Genetics and Metabolism, Department of Pediatrics, Children's Hospital Colorado 13123 East 16th Avenue, B153, Aurora, Colorado, USA. 12. Rare Disease Institute, Children's National Health System 111 Michigan Avenue, NW, Washington, District of Columbia 20010, USA.
Abstract
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.
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 transcarbamylasedeficiency (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 LOpatients 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 EOpatients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EOpatients 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.
Authors: Roland Posset; Angeles Garcia-Cazorla; Vassili Valayannopoulos; Elisa Leão Teles; Carlo Dionisi-Vici; Anaïs Brassier; Alberto B Burlina; Peter Burgard; Elisenda Cortès-Saladelafont; Dries Dobbelaere; Maria L Couce; Jolanta Sykut-Cegielska; Johannes Häberle; Allan M Lund; Anupam Chakrapani; Manuel Schiff; John H Walter; Jiri Zeman; Roshni Vara; Stefan Kölker Journal: J Inherit Metab Dis Date: 2016-04-22 Impact factor: 4.982
Authors: Mendel Tuchman; Brendan Lee; Uta Lichter-Konecki; Marshall L Summar; Marc Yudkoff; Stephen D Cederbaum; Douglas S Kerr; George A Diaz; Margaretta R Seashore; Hye-Seung Lee; Robert J McCarter; Jeffrey P Krischer; Mark L Batshaw Journal: Mol Genet Metab Date: 2008-06-17 Impact factor: 4.797
Authors: Brendan Lee; George A Diaz; William Rhead; Uta Lichter-Konecki; Annette Feigenbaum; Susan A Berry; Cindy Le Mons; James A Bartley; Nicola Longo; Sandesh C Nagamani; William Berquist; Renata Gallagher; Dennis Bartholomew; Cary O Harding; Mark S Korson; Shawn E McCandless; Wendy Smith; Stephen Cederbaum; Derek Wong; J Lawrence Merritt; Andreas Schulze; Jerry Vockley; Gerard Vockley; David Kronn; Roberto Zori; Marshall Summar; Douglas A Milikien; Miguel Marino; Dion F Coakley; Masoud Mokhtarani; Bruce F Scharschmidt Journal: Genet Med Date: 2014-12-11 Impact factor: 8.822
Authors: Roland Posset; Stefan Kölker; Florian Gleich; Jürgen G Okun; Andrea L Gropman; Sandesh C S Nagamani; Svenja Scharre; Joris Probst; Magdalena E Walter; Georg F Hoffmann; Sven F Garbade; Matthias Zielonka Journal: Mol Genet Metab Date: 2020-11-07 Impact factor: 4.797
Authors: Roland Posset; Andrea L Gropman; Sandesh C S Nagamani; Lindsay C Burrage; Jirair K Bedoyan; Derek Wong; Gerard T Berry; Matthias R Baumgartner; Marc Yudkoff; Matthias Zielonka; Georg F Hoffmann; Peter Burgard; Andreas Schulze; Shawn E McCandless; Angeles Garcia-Cazorla; Jennifer Seminara; Sven F Garbade; Stefan Kölker Journal: Ann Neurol Date: 2019-05-13 Impact factor: 10.422
Authors: Matthias Zielonka; Sven F Garbade; Florian Gleich; Jürgen G Okun; Sandesh C S Nagamani; Andrea L Gropman; Georg F Hoffmann; Stefan Kölker; Roland Posset Journal: Hum Mutat Date: 2020-01-30 Impact factor: 4.878
Authors: Roland Posset; Sven F Garbade; Florian Gleich; Andrea L Gropman; Pascale de Lonlay; Georg F Hoffmann; Angeles Garcia-Cazorla; Sandesh C S Nagamani; Matthias R Baumgartner; Andreas Schulze; Dries Dobbelaere; Marc Yudkoff; Stefan Kölker; Matthias Zielonka Journal: Sci Rep Date: 2020-07-20 Impact factor: 4.379
Authors: Matthias Zielonka; Stefan Kölker; Florian Gleich; Nicolas Stützenberger; Sandesh C S Nagamani; Andrea L Gropman; Georg F Hoffmann; Sven F Garbade; Roland Posset Journal: Ann Clin Transl Neurol Date: 2019-08-30 Impact factor: 4.511
Authors: Femke Molema; Diego Martinelli; Friederike Hörster; Stefan Kölker; Trine Tangeraas; Barbara de Koning; Carlo Dionisi-Vici; Monique Williams Journal: J Inherit Metab Dis Date: 2020-10-29 Impact factor: 4.982