Abstract
Background: Patients with organic acidurias (OAD) and urea cycle disorders (UCD) are at increased risk of disability, impaired quality of life and reduced life expectancy. Clinical care in any one centre is constrained by small patient numbers; and furthermore diagnostic and treatment strategies vary between metabolic centres and countries, resulting in significant inequalities and disparity in patient outcome.
Aims/methods: The overall objective of the EU-funded activity ‘European registry and network for intoxication type metabolic diseases’ (E-IMD) is to collect systematic data to improve the knowledge of these diseases, to develop consensus care guidelines and to provide detailed information materials for families and professionals.
Results: Within three years E-IMD has (1) established a network of 87 partners in 25 countries (2) set up a patient registry of more than 1,000 individuals with OAD and UCD, (3) launched a website (www.e-imd.org) including detailed information materials in 11 languages, (4) developed guidelines for OAD and UCD, (5) organised two teaching courses and various scientific meetings, (6) extended the IT platform clustering with other inherited metabolic diseases (IMD) and (7) strengthened the collaboration with other international scientific consortia.
Conclusions: E-IMD has made important steps towards improving and sharing knowledge on OAD and UCD and harmonisation of diagnostic and therapeutic strategies. Through the establishment of a modular patient registry, clustering with other IMD and stepwise extension of the network, E-IMD has implemented the core components of a European Reference Network for rare diseases.
Competing interests: None declared
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- EAHC:
-
European Agency for Health and Consumers
- E-HOD:
-
European network and registry for homocystinurias and methylation defects
- E-IMD:
-
European registry and network for intoxication type metabolic diseases
- ERN:
-
European reference network
- EUCERD:
-
European Union Committee of Experts on Rare Diseases
- GA1:
-
Glutaric aciduria type 1
- IMD:
-
Inherited metabolic disease
- IVA:
-
Isovaleric aciduria
- MMA:
-
Methylmalonic aciduria
- MS:
-
Member state
- OAD:
-
Organic aciduria
- PA:
-
Propionic aciduria
- PO:
-
Patient organisation
- UCD:
-
Urea cycle disorder
- UCDC:
-
Urea cycle disorders consortium
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Acknowledgements
This publication arises from the project ‘European registry and network for intoxication type metabolic diseases (E-IMD)’ (EAHC no 2010 12 01) which has received funding from the European Union, in the framework of the Health Programme. After the end of the EU funding period the E-IMD patient registry will be sustained by funding from the Kindness for Kids Foundation (Munich, Germany). MRB and JH are supported by radiz – Rare Disease Initiative Zurich – a clinical research priority programme of the University of Zurich, Switzerland.
We are grateful to the following partners for their valuable contribution to establish the E-IMD consortium and for their fruitful ongoing collaboration (listed in alphabetical order of countries):
Austria: Daniela Karall, Johannes Zschocke and Sabine Scholl-Bürgi (Medizinische Universität Innsbruck, Universitätskinderklinik und Sektionen für Humangenetik und Klinische Genetik, Innsbruck).
Australia: Avihu Boneh (the Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne)
Belgium: Francois Eyskens and Tine Maes (Universitair Ziekenhuis Antwerpen, Antwerpen), Linda de Meirleir (University Hospital Vrije Universiteit Brussels, Department of Pediatric Neurology, Brussels), Corinne de Laet (Hôpital Universitaire des Enfants Reine Fabiola, Nutrition and Metabolism Unit, Brussels), Etienne Sokal and Florence Defresne (Université Catholique de Louvain, Clinique Universitaires St. Luc, Brussels), Dominique Roland (Institute of Pathology and Genetics, Center for Inherited Metabolic Diseases, Gosselies), Guillaume Debray (Centre Hospitalier Universitaire, Department of Genetics, Liège) and Lut de Baere and Nathalie Stroobant [Belgische Organisatie voor Kinderen en Volwassenen met een Stofwisselingsziekte VZW (BOKS), Melsele, PO group]
Canada: Cheryl R. Greenberg (University of Manitoba, Department of Pediatrics and Child Health, Department of Biochemistry and Medical Genetics, Winnipeg)
Croatia: Ivo Baric, Mario Cuk and Slobodan Galic (Sveuciliste u Zagrebu, Medicinski fakultet, University Hospital Centre, Department of Pediatrics, Zagreb) and Nelia Caric (Hrvatska udruga za rijetke bolesti, PO group)
Czech Republic: Jiri Zeman and Tomas Honzik (Charles University of Prague, First Faculty of Medicine, Department of Pediatrics, Prague)
Denmark: Allan M. Lund, Ernst Christensen, Lise Aksglaede and Malene Bøgehus Rasmussen (Rigshospitalet, Centre for Inherited Metabolic Diseases, Department of Clinical Genetics, Copenhagen) and Annika and Kennet Rovsing (PND – Protein Nedbrydnings Defekt foreningen, PO group)
France: Vassili Valayannopoulos, Jean-Baptiste Arnoux, Pascale de Lonlay, Ulf Aringer, Kim-Hanh Le Quan Sang and Eric Bauchart (Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Reference Center for Inherited Metabolic Disease, Necker-Enfants Malades University Hospital and Imagine Institute, Paris); Hélène Ogier de Baulny (Centre de Référence Maladies Héréditaires du Metabolisme, Hôpital Robert Debré, Université Paris VII, Paris); Brigitte Chabrol (Centre de Référence Maladies Héréditaires du Metabolisme, Hôpital d’Enfants Service de Neurologie, Marseille); Pierre Broue (Centre de Référence Maladies Héréditaires du Metabolisme, Hôpital des Enfants – CHU Toulouse, Toulouse); EURORDIS, European Organisation for Rare Disease (Paris); and Orphan Europe SARL (Paris)
Germany: S. P. Nikolas Boy, Corinna Bürger, Esther M. Glahn, Friederike Hörster, Gisela Haege, Jana Heringer, Marina A. Morath, Roland Posset, Christian Staufner, Kathrin Zangerl and Matthias Zielonka (Universitätsklinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin, Kinderklinik I); Chris Mühlhausen and René Santer (Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendmedizin, Hamburg); Regina Ensenauer (Ludwig-Maximilian-Universität München, Dr. von Haunersches Kinderspital, München); Thomas Meissner (Universitätsklinikum Düsseldorf, Zentrum für Kinder- und Jugendmedizin, Düsseldorf); Peter Freisinger (Klinik für Kinder- und Jugendmedizin, Klinikum am Steinenberg, Reutlingen); Sarah Grünert and Ute Spiekerkötter (Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin, Freiburg); Martin Lindner (Universitätsklinikum Frankfurt, Klinik für Kinder- und Jugendmedizin, Frankfurt); Markus Ott and Beate Szczerbak (Nutricia Metabolics GmbH, Friedrichsdorf); Hubertus von Voss and Raimund Schmid (Kindernetzwerk e.V., Aschaffenburg); Mandy Kretschmer (Glutarazidurie e.V.); and Reinhild Link (Wiesbaden, representing the SSIEM Dieticians Group)
Greece: Persephone Augoustides-Savvopoulou and Harikleia Ioannou (University A’Pediatric Department, Metabolic Laboratory, ‘Hippokration’ General Hospital of Thessaloniki, Thessaloniki, and KRIKOS ZOIS, PO group), Evriki Drogari (University of Athens, Aghia Sophia Children’s Hospital, Unit of Metabolic Diseases, Athens) and Zarifis Dimitroulis (KRIKOS ZOIS – Society for Patients and Friends of Patients with Inherited Metabolic diseases, PO group)
India: Anil Jalan (N.I.R.M.A.N., Om Rachna Society, Mumbai)
Italy: Alberto B. Burlina, Andrea Bordugo and Francesca Furlan (Azienda Ospedaliera di Padova, U.O.C. Malattie Metaboliche Ereditarie, Dipartimento di Pediatria, Padova); Carlo Dionisi-Vici and Diego Martinelli (Ospedale Pediatrico Bambino Gesù, U.O.C. Patologia Metabolica, Rome); Renza Barbon Galluppi (UNIAMO FIMR, PO group); and Susan Udina (COMETA ASMME – Associazione Studio Malattie Metaboliche Ereditarie – ONLUS, PO group)
Japan: Fumio Endo and Shirou Matsumoto (Kumamoto University Hospital, Department of Pedatrics, Kumamoto, and representing the Japanese Urea Cycle Disorders Consortium)
Netherlands: Frits A. Wijburg and Eveline Langereis (Academisch Medisch Centrum, Department of Pediatrics, Amsterdam), Monique Williams (Erasmus Universiteit Rotterdam, Erasmus MC-Sophia Kinderziekenhuis, Rotterdam) and Hanka Meutgeert (Volwassenen en Kinderen met Stofwisselingsziekten [VKS], Zwolle, PO group)
Poland: Jolanta Sykut-Cegielska (Institute of Mother and Child, Screening Department, Warsaw) and Wanda Gradowska (Instytut ‘Pomnik-Centrum Zdrowia Dziecka’, The Children’s Memorial Health Institute, Department of Metabolic Diseases, Endocrinology and Diabetology, Warsaw)
Portugal: Elisa Teles Leao, Susana Soares and Esmeralda Rodrigues (Unidade de Doenças Metabólicas, Serviço de Pediatria, Hospital de S. João, EPE, Porto); Laura Vilarinho (Newborn Screening Unit, Metabolic Genetics Center, National Institute of Health [INSA], Porto); Ana Gaspar (Unidade de Doenças Metabólicas, Serviço de Pediatria Hospital Santa Maria Lisboa, Lisbon); Isabel Tavares de Almeida (Faculdade de Farmácia da Universidade de Lisboa, Lisbon); Vanessa Ferreira (Associação Portuguesa CDG, PO group); Miguel Macedo (Apofen, PO group); and Sérgio Braz Antão (Rarrisimas, PO group)
Republic of Serbia: Adrijan Sarajlija and Maja Djordjevic (Institut za zdravstvenu zaštitu majke i deteta Srbije, Belgrade)
Romania: Paula Avram (Institute for Mother and Child Care ‘Alfred Rusescu’, Bucharest)
Spain: Juan-Luque Moreno (CIBERER, Centro de Investigacíon Biomédica en Red de Enfermedades Raras); Angeles Garcia-Cazorla, Jaume Campistol, Carlos Ortez and Elisenda Cortès i Saladelafont (Hospital Sant Joan de Deu, Servicio de Neurologica, Barcelona); Elena Balmaseda and M. Carmen Carrascosa (Complejo Hospitalario Universitario de Albacete, Albacete); Guillem Pintos-Morell (University hospital ‘German Trias i Pujol’, Badalona); Antonia Ribes (Institut Bioquimica Clinica, Corporacio Sanitaria Clinic, Barcelona); Eduardo Lopéz (Pediatric Neurology Unit Department of Pediatrics, University Hospital Reina Sofia, Cordoba); Immaculada Vives and David Gil Ortega (Hospital Virgen de la Arrixaca de Murcia, El Palmar); Juana Maria de Haro Catellano (Secretaria Tecnica del CEI-Granada (HUVN), Edificio Licinio de la Fuente, Granada); Luis Pena-Quintana (Hospital Universitario Materno-Infantil de Canarias, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria); Magdalena Ugarte and Begona Merinero (Universidad Autonoma de Madrid, Madrid); Consuelo Pedròn-Giner (Hospital Infantil Universitario Niño Jesús, Sección de Gastroenterología y Nutrición, Madrid); Javier Blasco-Alonso (Hospital Materno-Infantil de Malaga, Unidad de Gastroenterologia, Hepatologia, Nutricion y Metabolopatias, Malaga); Angeles Ruiz Gómez (Hospital Universitario Son Espases, Palma de Mallorca); Maria L. Couce (Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela); Vicente Rubio (Instituto de Biomedicina de Valencia, Valencia); and Sergi Faber (Catalana de Trastorns Metabòlics Hereditaris, PO group)
Sweden: Sofia Nordin (Swedish Orphan Biovitrum AB [SOBI], Stockholm)
Switzerland: Jörn-Oliver Sass (Kinderspital Zürich, Universitäts-Kinderkliniken, Eleonoren-Stiftung, Department of Clinical Chemistry and Biochemistry, Zürich) and Jean-Marc Nuoffer (Universitätsspital Bern, Universitätsklinik für Kinderheilkunde, Bern)
Taiwan: Wu-Liang Hwu, Yin-Hsiu Chien and Ni-Chung Lee (National Taiwan University Hospital, Department of Medical Genetics, Taipei)
Turkey: Mübeccel Demirkol and Gülden Gökcay (Istanbul University, Children’s Hospital, Department of Nutrition and Metabolism, Istanbul)
UK: Victoria Riches (Birmingham Children’s Hospital NHS Foundation Trust, Birmingham); CLIMB, Children Living with Inherited Metabolic Diseases, National Information Centre for Metabolic Diseases (Crewe); Stephanie Grünewald and Nick Thompson (Great Ormond Street Hospital for Children NHS Trust, London); Robin Lachmann and Elaine Murphy (National Hospital for Neurology and Neurosurgery, Charles Dent Metabolic Unit, London, and representing the SSIEM Adult Metabolic Group); Roshni Vara (Evelina Children’s Hospital, St Thomas’ Hospital, Department of Inherited Metabolic Disease, London); John Walter and Andrew Morris (Central Manchester and Manchester Children’s University Hospital, Willink Biochemical Genetics Unit, Manchester); Bradford Teaching Hospitals NHS Trust, St Luke’s Hospital (Bradford); and EMDA, the European Metabolic Disorders Alliance (PO group)
USA: Kimberly Chapman (Children’s National Medical Center, Center for Genetic Medicine Research, Washington DC, and representing the Urea Cycle Disorders Consortium) and Jerry Vockley (Children’s Hospital of Pittsburgh of UPMC, Pittsburgh)
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Communicated by: Bridget Wilcken
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Synopsis
E-IMD has established an international network, has improved knowledge about organic acidurias and urea cycle disorders and has started harmonising diagnostic and therapeutic strategies. This is the prerequisite for establishing a European Reference Network for inherited metabolic diseases.
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Conflict of Interest
Stefan Kölker, Matthias R. Baumgartner, Peter Burgard, Anupam Chakrapani, Dries Dobbelaere, Florian Gleich, Johannes Häberle, Marshall L. Summar, and Steven Hannigan declare that they have no conflict of interest. Samantha Parker is employed by Orphan Europe Sarl being part of the Recordati Group.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients or their legal guardians for being included in the study.
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Statistical analysis: Peter Burgard, Florian Gleich and Stefan Kölker
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Kölker, S. et al. (2015). Networking Across Borders for Individuals with Organic Acidurias and Urea Cycle Disorders: The E-IMD Consortium. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 22. JIMD Reports, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_408
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