title: Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases.
abstract: BACKGROUND
  Advances in the diagnosis and treatment of urea cycle disorders (UCDs) have led to a higher survival rate. The purpose of this study is to describe the characteristics of patients with urea cycle disorders in Spain.
  
  
  METHODS
  Observational, cross-sectional and multicenter study. Clinical, biochemical and genetic data were collected from patients with UCDs, treated in the metabolic diseases centers in Spain between February 2012 and February 2013, covering the entire Spanish population. Heterozygous mothers of patients with OTC deficiency were only included if they were on treatment due to being symptomatic or having biochemistry abnormalities.
  
  
  RESULTS
  104 patients from 98 families were included. Ornithine transcarbamylase deficiency was the most frequent condition (64.4%) (61.2% female) followed by type 1 citrullinemia (21.1%) and argininosuccinic aciduria (9.6%). Only 13 patients (12.5%) were diagnosed in a pre-symptomatic state. 63% of the cases presented with type intoxication encephalopathy. The median ammonia level at onset was 298 μmol/L (169-615). The genotype of 75 patients is known, with 18 new mutations having been described. During the data collection period four patients died, three of them in the early days of life. The median current age is 9.96 years (5.29-18), with 25 patients over 18 years of age. Anthropometric data, expressed as median and z-score for the Spanish population is shown. 52.5% of the cases present neurological sequelae, which have been linked to the type of disease, neonatal onset, hepatic failure at diagnosis and ammonia values at diagnosis. 93 patients are following a protein restrictive diet, 0.84 g/kg/day (0.67-1.10), 50 are receiving essential amino acid supplements, 0.25 g/kg/day (0.20-0.45), 58 arginine, 156 mg/kg/day (109-305) and 45 citrulline, 150 mg/kg/day (105-199). 65 patients are being treated with drugs: 4 with sodium benzoate, 50 with sodium phenylbutyrate, 10 with both drugs and 1 with carglumic acid.
  
  
  CONCLUSIONS
  Studies like this make it possible to analyze the frequency, natural history and clinical practices in the area of rare diseases, with the purpose of knowing the needs of the patients and thus planning their care.
authors.affiliation: Pediatric Rares Diseases Unit, Metabolic and Mitochondrial Diseases, Pediatric Department, Hospital Universitario 12 de Octubre. Research Institute (i +12), Madrid, Spain, Avda de Córdoba s/n, 28041, Madrid, Spain. emartinhernandez@salud.madrid.org.
authors.forename: Elena
authors.initials: E
authors.lastname: Martín-Hernández
authors.affiliation: H.U. de Cruces, Bilbao, Spain. luisjose.aldamiz-echevarazuara@osakidetza.net.
authors.forename: Luis
authors.initials: L
authors.lastname: Aldámiz-Echevarría
authors.affiliation: H. Sant Joan de Déu, Barcelona, Spain. ecastejon@hsjdbcn.org.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Castejón-Ponce
authors.affiliation: H.U. Infantil del Niño Jesús, Madrid, Spain. cpedron.hnjs@salud.madrid.org.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Pedrón-Giner
authors.affiliation: C.H.U. de Santiago, Santiago de Compostela, Spain. Maria.Luz.Couce.Pico@sergas.es.
authors.forename: María Luz
authors.initials: ML
authors.lastname: Couce
authors.affiliation: H. Materno Infantil Carlos Haya, Málaga, Spain. serranonieto@hotmail.com.
authors.forename: Juliana
authors.initials: J
authors.lastname: Serrano-Nieto
authors.affiliation: H.U. Germans Trias i Pujol, Badalona, Spain. gpintos.germanstrias@gencat.cat.
authors.forename: Guillem
authors.initials: G
authors.lastname: Pintos-Morell
authors.affiliation: H.U. Ramón y Cajal, Madrid, Spain. amaya.belanger@salud.madrid.org.
authors.forename: Amaya
authors.initials: A
authors.lastname: Bélanger-Quintana
authors.affiliation: H.U. Ramón y Cajal, Madrid, Spain. mmartinezc.hrc@salud.madrid.org.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Martínez-Pardo
authors.affiliation: Pediatric Rares Diseases Unit, Metabolic and Mitochondrial Diseases, Pediatric Department, Hospital Universitario 12 de Octubre. Research Institute (i +12), Madrid, Spain, Avda de Córdoba s/n, 28041, Madrid, Spain. mgarciasilva@salud.madrid.org.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: García-Silva
authors.affiliation: Pediatric Rares Diseases Unit, Metabolic and Mitochondrial Diseases, Pediatric Department, Hospital Universitario 12 de Octubre. Research Institute (i +12), Madrid, Spain, Avda de Córdoba s/n, 28041, Madrid, Spain. pilar.quijadaf@salud.madrid.org.
authors.forename: Pilar
authors.initials: P
authors.lastname: Quijada-Fraile
authors.affiliation: H. Infantil La Fe, Valencia, Spain. vitoria_isi@gva.es.
authors.forename: Isidro
authors.initials: I
authors.lastname: Vitoria-Miñana
authors.affiliation: H. Infantil La Fe, Valencia, Spain. dalmau_jai@gva.es.
authors.forename: Jaime
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: H.U. La Paz, Madrid, Spain. maquedalama@gmail.com.
authors.forename: Rosa A
authors.initials: RA
authors.lastname: Lama-More
authors.affiliation: H.U. Virgen del Rocío, Sevilla, Spain. mbuenod@yahoo.es.
authors.forename: María Amor
authors.initials: MA
authors.lastname: Bueno-Delgado
authors.affiliation: H. Vall d'Hebrón, Barcelona, Spain. mdeltoro@vhebron.net.
authors.forename: Mirella
authors.initials: M
authors.lastname: Del Toro-Riera
authors.affiliation: H.U. Miguel Servet, Zaragoza, Spain. igarciaji@salud.aragon.es.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: García-Jiménez
authors.affiliation: C.H. de Jaén, Jaén, Spain. conchasierra@hotmail.com.
authors.forename: Concepción
authors.initials: C
authors.lastname: Sierra-Córcoles
authors.affiliation: H.U. Ntra. Sra. de la Candelaria, Santa Cruz de Tenerife, Spain. monicarpons@yahoo.es.
authors.forename: Mónica
authors.initials: M
authors.lastname: Ruiz-Pons
authors.affiliation: H.U. Materno Infantil de Las Palmas, Las Palmas de Gran Canaria, Spain. lpenqui@gobiernodecanarias.org.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Peña-Quintana
authors.affiliation: H.C.U. Virgen de la Arrixaca, Murcia, Spain. vivesmas@hotmail.com.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Vives-Piñera
authors.affiliation: H.U. La Paz, Madrid, Spain. morais.lopez@salud.madrid.org.
authors.forename: Ana
authors.initials: A
authors.lastname: Moráis
authors.affiliation: C.H.U. de Albacete, Albacete, Spain. elenabalmaseda@hotmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Balmaseda-Serrano
authors.affiliation: H. Sant Joan de Déu, Barcelona, Spain. smeavillao@hsjdbcn.org.
authors.forename: Silvia
authors.initials: S
authors.lastname: Meavilla
authors.affiliation: H.U. de Cruces, Bilbao, Spain. PABLO.SANJURJOCRESPO@osakidetza.net.
authors.forename: Pablo
authors.initials: P
authors.lastname: Sanjurjo-Crespo
authors.affiliation: CEDEM. Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain. cpcerda@cbm.uam.es.
authors.forename: Celia
authors.initials: C
authors.lastname: Pérez-Cerdá
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D013030:Spain / Q000453:epidemiology; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics*; D055815:Young Adult