title: Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001-2013.
abstract: Urea cycle disorders (UCDs) are rare inherited metabolic defects of ammonia detoxification. In about half of patients presenting with a UCD, the first symptoms appear within a few days after birth. These neonatal onset patients generally have a severe defect of urea cycle function and their survival and outcome prognoses are often limited. To understand better the current situation of neonatal onset in UCDs, we have performed a multicentre, retrospective, non-interventional case series study focussing on the most severe UCDs, namely defects of carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (ASS).
  
  
  
  Data of 63 patients were collected (27 patients with ASS deficiency, 23 patients with OTC deficiency, and 12 patients with CPS1 deficiency, one patient definite diagnosis not documented). The majority of patients (43/63, 68 %) had an initial ammonia concentration exceeding 500 μmol/L (normal < 100), of which most (26/43, 60.5 %) were also encephalopathic and were treated with hemodialysis. In patients surviving the initial crisis, recurrence of hyperammonemic events within the first 1.5 years of life occurred frequently (mean 3.6 events, range 0-20). Of all patients, 16 (25.4 %) died during or immediately after the neonatal period.
  
  
  
  We observed in this cohort of neonatal onset UCD patients a high rate of initial life-threatening hyperammonemia and a high risk of recurrence of severe hyperammonemic crises. These corresponded to a high mortality rate during the entire study period (30.2 %) despite the fact that patients were treated in leading European metabolic centers. This underlines the need to critically re-evaluate the current treatment strategies in these patients.
authors.affiliation: Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, 8032, Zürich, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Unsinn
authors.affiliation: Department of Paediatrics, Medical School Hannover, Hannover, Germany.
authors.forename: Anibh
authors.initials: A
authors.lastname: Das
authors.affiliation: Reference Center for Inherited Metabolic Disorders, Necker-Enfants Malades University Hospital and IMAGINE Institute, Paris, France.
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.affiliation: University Children's Hospital, Düsseldorf, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Thimm
authors.affiliation: Hospital for Children and Adolescents, Centre of Paediatric Research (CPR), University of Leipzig, Leipzig, Germany.
authors.forename: Skadi
authors.initials: S
authors.lastname: Beblo
authors.affiliation: Department of Pediatrics University Hospital, Division of Inherited Metabolic Disorders, Padova, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Burlina
authors.affiliation: University Children's Hospital, Vienna, Austria.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Konstantopoulou
authors.affiliation: Department of Paediatrics, Medical School Hannover, Hannover, Germany.
authors.forename: Sebene
authors.initials: S
authors.lastname: Mayorandan
authors.affiliation: Reference Center for Inherited Metabolic Disorders, Necker-Enfants Malades University Hospital and IMAGINE Institute, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.affiliation: Cytonet GmbH & Co. KG, Weinheim, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rennecke
authors.affiliation: Cytonet GmbH & Co. KG, Weinheim, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Derbinski
authors.affiliation: Department of Pediatrics, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Division of Metabolism and Children's Research Center, University Children's Hospital Zurich, 8032, Zürich, Switzerland. Johannes.Haeberle@kispi.uzh.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
mesh_terms: D001120:Arginine / Q000627:therapeutic use; D002675:Child, Preschool; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D007223:Infant; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D008297:Male; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D020160:Sodium Benzoate / Q000627:therapeutic use; D056806:Urea Cycle Disorders, Inborn / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery
chemical_list: D001120:Arginine; D020160:Sodium Benzoate
keywords: Argininosuccinate synthetase deficiency; Carbamoyl phosphate synthetase 1 deficiency; Dialysis; Ornithine transcarbamylase deficiency; Urea cycle disorders; hyperammonemic crisis; neonatal hyperammonemia