title: The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation.
abstract: BACKGROUND
  The clinical presentation of patients with organic acidurias (OAD) and urea cycle disorders (UCD) is variable; symptoms are often non-specific.
  
  
  OBJECTIVE
  To improve the knowledge about OAD and UCD the E-IMD consortium established a web-based patient registry.
  
  
  RESULTS
  We registered 795 patients with OAD (n = 452) and UCD (n = 343), with ornithine transcarbamylase (OTC) deficiency (n = 196), glutaric aciduria type 1 (GA1; n = 150) and methylmalonic aciduria (MMA; n = 149) being the most frequent diseases. Overall, 548 patients (69 %) were symptomatic. The majority of them (n = 463) presented with acute metabolic crisis during (n = 220) or after the newborn period (n = 243) frequently demonstrating impaired consciousness, vomiting and/or muscular hypotonia. Neonatal onset of symptoms was most frequent in argininosuccinic synthetase and lyase deficiency and carbamylphosphate 1 synthetase deficiency, unexpectedly low in male OTC deficiency, and least frequently in GA1 and female OTC deficiency. For patients with MMA, propionic aciduria (PA) and OTC deficiency (male and female), hyperammonemia was more severe in metabolic crises during than after the newborn period, whereas metabolic acidosis tended to be more severe in MMA and PA patients with late onset of symptoms. Symptomatic patients without metabolic crises (n = 94) often presented with a movement disorder, mental retardation, epilepsy and psychiatric disorders (the latter in UCD only).
  
  
  CONCLUSIONS
  The initial presentation varies widely in OAD and UCD patients. This is a challenge for rapid diagnosis and early start of treatment. Patients with a sepsis-like neonatal crisis and those with late-onset of symptoms are both at risk of delayed or missed diagnosis.
authors: Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany. Stefan.Koelker@med.uni-heidelberg.de.
authors: Stefan
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authors: Servicio de Neurologia and CIBERER, ISCIII, Hospital San Joan de Deu, Barcelona, Spain.
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authors: Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Reference Center for Inherited Metabolic Disease, Necker-Enfants Malades University Hospital and IMAGINE Institute, Paris, France.
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authors: Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria.
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authors: 1st Pediatric Department, Metabolic Laboratory, General Hospital of Thessaloniki 'Hippocration', Thessaloniki, Greece.
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authors: Servicio de Neurologia and CIBERER, ISCIII, Hospital San Joan de Deu, Barcelona, Spain.
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authors: Metabolic Unit, Department of Pediatrics, Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
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authors: Dobbelaere
authors: First Faculty of Medicine, Charles University and General University of Prague, Prague, Czech Republic.
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authors: U.O.C. Malattie Metaboliche Ereditarie, Azienda Ospedaliera di Padova, Padova, Italy.
authors: Francesca
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authors: Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors: Florian
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authors: Gleich
authors: Department of Laboratory Diagnostics, The Children's Memorial Health Institute, Warsaw, Poland.
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authors: Gradowska
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authors: Division of Metabolism and Children's Research Centre, University Children's Hospital Zurich, Steinwiesstraße 75, CH-8032, Zurich, Switzerland.
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authors: Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
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authors: Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Reference Center for Inherited Metabolic Disease, Necker-Enfants Malades University Hospital and IMAGINE Institute, Paris, France.
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authors: de Lonlay
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authors: Rodrigues
authors: Clinic for Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria.
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authors: Service Gastroentérologie and Hépatologie Pédiatrique, Cliniques Universitaires St Luc, Université Catholique de Louvain, Bruxelles, Belgium.
authors: Etienne
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authors: Sokal
authors: Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
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authors: Children's National Medical Center, 111 Michigan Avenue, N.W., Washington, DC, 20010, USA.
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authors: Inborn Metabolic Disease Unit, Hospital Virgen de la Arrixaca de Murcia, El Palmar, Spain.
authors: Inmaculada Vives
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authors: Pinera
authors: Manchester Academic Health Science Centre, Willink Biochemical Genetics Unit, Genetic Medicine, University of Manchester, Manchester, UK.
authors: John H
authors: JH
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authors: Erasmus MC-Sophia Kinderziekenhuis, Erasmus Universiteit Rotterdam, Rotterdam, Netherlands.
authors: Monique
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authors: Williams
authors: Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
authors: Peter
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authors: Burgard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis*; D001928:Brain Diseases, Metabolic / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D005060:Europe; D005260:Female; D050770:Glutaryl-CoA Dehydrogenase / Q000172:deficiency*; D006801:Humans; D022124:Hyperammonemia / Q000175:diagnosis*; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability; D008297:Male; D008875:Middle Aged; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000175:diagnosis*; D012042:Registries; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis*; D014839:Vomiting; D055815:Young Adult
chemical_list: D050770:Glutaryl-CoA Dehydrogenase