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Exclusion of asfOTC\u2010D 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 (\u2264 28\u2009days) 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\u2010D), diagnosis was made after the onset of symptoms (59.9%) or by high\u2010risk 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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\u2010term outcome studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jimd.12031","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T08:08:54Z","timestamp":1549872534000},"page":"93-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders\u2014A successful strategy for clinical research of rare diseases"],"prefix":"10.1002","volume":"42","author":[{"given":"Roland","family":"Posset","sequence":"first","affiliation":[{"name":"Centre for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Inherited Metabolic Diseases University Hospital Heidelberg, Im Neuenheimer Feld 430 69120  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[{"name":"Centre for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Inherited Metabolic Diseases University Hospital Heidelberg, Im Neuenheimer Feld 430 69120  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas","family":"Boy","sequence":"additional","affiliation":[{"name":"Centre for Pediatric and Adolescent Medicine, Division of Neuropediatrics and Inherited Metabolic Diseases University Hospital Heidelberg, Im Neuenheimer Feld 430 69120  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto B.","family":"Burlina","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera di Padova U.O.C. Malattie Metaboliche Ereditarie  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Dionisi\u2010Vici","sequence":"additional","affiliation":[{"name":"Ospedale Pediatrico Bambino G\u00e9su U.O.C. Patologia Metabolica  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dries","family":"Dobbelaere","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies H\u00e9r\u00e9ditaires du M\u00e9tabolisme 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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeles","family":"Garcia\u2010Cazorla","sequence":"additional","affiliation":[{"name":"Hospital San Joan de Deu Institut Pedi\u00e0tric de Recerca, Servicio de Neurologia and CIBERER, ISCIII  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"de Lonlay","sequence":"additional","affiliation":[{"name":"Service de Maladies M\u00e9taboliques H\u00f4pital Necker\u2010Enfants Malades Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa Le\u00e3o","family":"Teles","sequence":"additional","affiliation":[{"name":"Unidade de Doen\u00e7as Metab\u00f3licas Servi\u00e7o de Pediatria, Hospital de S. 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