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In fact, NBS lowered the age at diagnosis in patients with late onset of symptoms (&gt;28 days), and a trend towards improved long\u2010term neurological outcome was found for patients with argininosuccinate synthetase and lyase deficiency as well as argininemia identified by NBS. Three to 17 different drug combinations were used for maintenance therapy, but superiority of any single drug or specific drug combination above other combinations was not demonstrated. Importantly, non\u2010interventional variables of disease severity, such as age at disease onset and peak ammonium level of the initial hyperammonemic crisis (cut\u2010off level: 500 \u03bcmol\/L) best predicted the neurological outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Promising results of NBS for late onset UCD patients are reported and should be re\u2010evaluated in a larger and more advanced age group. However, non\u2010interventional variables affect the neurological outcome of UCD patients. Available evidence\u2010based guideline recommendations are currently heterogeneously implemented into practice, leading to a high variability of drug combinations that hamper our understanding of optimised long\u2010term and emergency treatment.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-016-9938-9","type":"journal-article","created":{"date-parts":[[2016,4,22]],"date-time":"2016-04-22T09:42:15Z","timestamp":1461318135000},"page":"661-672","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders"],"prefix":"10.1002","volume":"39","author":[{"given":"Roland","family":"Posset","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Division of Inherited Metabolic Diseases University Children's Hospital Heidelberg Im Neuenheimer Feld 430 Heidelberg D\u201069120 Germany"}]},{"given":"Angeles","family":"Garcia\u2010Cazorla","sequence":"additional","affiliation":[{"name":"Hospital San Joan de Deu, Servicio de Neurologia and CIBERER, ISCIII Barcelona Spain"}]},{"given":"Vassili","family":"Valayannopoulos","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, Service de Maladies Metaboliques H\u00f4pital Necker\u2010Enfants Malades Paris France"}]},{"given":"Elisa Le\u00e3o","family":"Teles","sequence":"additional","affiliation":[{"name":"Hospital de S. 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Malattie Metaboliche Ereditarie Padova Italy"}]},{"given":"Peter","family":"Burgard","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Inherited Metabolic Diseases University Children's Hospital Heidelberg Im Neuenheimer Feld 430 Heidelberg D\u201069120 Germany"}]},{"given":"Elisenda","family":"Cort\u00e8s\u2010Saladelafont","sequence":"additional","affiliation":[{"name":"Hospital San Joan de Deu, Servicio de Neurologia and CIBERER, ISCIII Barcelona Spain"}]},{"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 Lille 59037 France"}]},{"given":"Maria L.","family":"Couce","sequence":"additional","affiliation":[{"name":"Metabolic Unit, Department of Pediatrics Hospital Clinico Universitario de Santiago de Compostela Santiago de Compostela Spain"}]},{"given":"Jolanta","family":"Sykut\u2010Cegielska","sequence":"additional","affiliation":[{"name":"Screening Department Institute of Mother and Child Warsaw Poland"}]},{"given":"Johannes","family":"H\u00e4berle","sequence":"additional","affiliation":[{"name":"Division of Metabolism and Children's Research Centre University Children's Hospital Zurich Steinwiesstra\u00dfe 75 Zurich CH\u20108032 Switzerland"}]},{"given":"Allan M.","family":"Lund","sequence":"additional","affiliation":[{"name":"Centre for Inherited Metabolic Diseases, Department of Clinical Genetics Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"}]},{"given":"Anupam","family":"Chakrapani","sequence":"additional","affiliation":[{"name":"Birmingham Children's Hospital NHS Foundation Trust Steelhouse Lane Birmingham B4 6NH UK"},{"name":"Metabolic Unit Great Ormond Street Hospital and Institute for Child Health University College London London UK"}]},{"given":"Manuel","family":"Schiff","sequence":"additional","affiliation":[{"name":"H\u00f4pital Robert Debr\u00e9, Reference Centre for Inborn Errors of Metabolism APHP and Universit\u00e9 Paris\u2010Diderot Paris France"}]},{"given":"John H.","family":"Walter","sequence":"additional","affiliation":[{"name":"Manchester Academic Health Science Centre, Willink Biochemical Genetics Unit, Genetic Medicine University of Manchester Manchester UK"}]},{"given":"Jiri","family":"Zeman","sequence":"additional","affiliation":[{"name":"First Faculty of Medicine Charles University and General University of Prague Prague Czech Republic"}]},{"given":"Roshni","family":"Vara","sequence":"additional","affiliation":[{"name":"Evelina Children's Hospital, St Thomas\u2019 Hospital London UK"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Inherited Metabolic Diseases University Children's Hospital Heidelberg Im Neuenheimer Feld 430 Heidelberg D\u201069120 Germany"}]},{"name":"Additional individual contributors of the E\u2010IMD consortium","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2016,4,22]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.09.003"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-003-1347-z"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-003-1347-z"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.08.001"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.02.007"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0266-1"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)90518-X"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(79)91503-4"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-012-9484-z"},{"key":"e_1_2_13_11_1","doi-asserted-by":"crossref","unstructured":"BurgardPK\u00f6lkerSHaegeGLindnerMHoffmannGFNeonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders \u2013 review and meta\u2010analysis of observational studies published over more than 35 yearsJ Inherit Metab Dis2015.","DOI":"10.1007\/s10545-015-9901-1"},{"key":"e_1_2_13_12_1","volume-title":"R Foundation for Statistical Computing","author":"R Core Team","year":"2015"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.11.004"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066596"},{"key":"e_1_2_13_15_1","volume-title":"Human energy requirements: report of a joint FAO\/WHO\/UNU expert consultation. 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