Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases


Por: Martin-Hernandez, E, Aldamiz-Echevarria, L, Castejon-Ponce, E, Pedron-Giner, C, Couce, ML, Serrano-Nieto, J, Pintos-Morell, G, Belanger-Quintana, A, Martinez-Pardo, M, Garcia-Silva, MT, Quijada-Fraile, P, Vitoria-Minana, I, Dalmau, J, Lama-More, RA, Bueno-Delgadi, MA, del Toro-Riera, M, Garcia-Jimenez, I, Sierra-Corcoles, C, Ruiz-Pons, M, Pena-Quintana, LJ, Vives-Pinera, I, Morais, A, Balmaseda-Serrano, E, Meavilla, S, Sanjurjo-Crespo, P and Perez-Cerda, C

Publicada: 30 nov 2014
Resumen:
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 mu mol/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.

Filiaciones:
Martin-Hernandez, E:
 Hosp Univ 12 Octubre, Res Inst 1 12, Pediat Rares Dis Unit, Dept Pediat, Madrid 28041, Spain

Aldamiz-Echevarria, L:
 Hosp Univ Cruces, Bilbao, Spain

Castejon-Ponce, E:
 Hosp St Joan de Deu, Barcelona, Spain

Pedron-Giner, C:
 Hosp Univ Infantil Nino Jesus, Madrid, Spain

Couce, ML:
 CHU Santiago, Santiago De Compostela, Spain

Serrano-Nieto, J:
 H Materno Infantil Carlos Haya, Malaga, Spain

:
 Hosp Badalona Germans Trias & Pujol, Badalona, Spain

Belanger-Quintana, A:
 Hosp Univ Ramon & Cajal, Madrid, Spain

Martinez-Pardo, M:
 Hosp Univ Ramon & Cajal, Madrid, Spain

Garcia-Silva, MT:
 Hosp Univ 12 Octubre, Res Inst 1 12, Pediat Rares Dis Unit, Dept Pediat, Madrid 28041, Spain

Quijada-Fraile, P:
 Hosp Univ 12 Octubre, Res Inst 1 12, Pediat Rares Dis Unit, Dept Pediat, Madrid 28041, Spain

Vitoria-Minana, I:
 Hosp Infantil La Fe, Valencia, Spain

Dalmau, J:
 Hosp Infantil La Fe, Valencia, Spain

Lama-More, RA:
 Hosp Univ La Paz, Madrid, Spain

Bueno-Delgadi, MA:
 Hosp Univ Virgen Rocio, Seville, Spain

del Toro-Riera, M:
 Hosp Valle De Hebron, Barcelona, Spain

Garcia-Jimenez, I:
 Hosp Univ Miguel Servet, Zaragoza, Spain

Sierra-Corcoles, C:
 Ctr Hosp Jaen, Jaen, Spain

Ruiz-Pons, M:
 Hosp Univ Ntra Sra Candelaria, Santa Cruz De Tenerife, Spain

Pena-Quintana, LJ:
 Hosp Univ Materno Infantil Las Palmas, Las Palmas Gran Canaria, Spain

Vives-Pinera, I:
 Hosp Ctr Univ Virgen Arrixaca, Murcia, Spain

Morais, A:
 Hosp Univ La Paz, Madrid, Spain

Balmaseda-Serrano, E:
 CHU Albacete, Albacete, Spain

Meavilla, S:
 Hosp St Joan de Deu, Barcelona, Spain

Sanjurjo-Crespo, P:
 Hosp Univ Cruces, Bilbao, Spain

Perez-Cerda, C:
 Univ Autonoma Madrid, Fac Ciencias, CEDEM, E-28049 Madrid, Spain
ISSN: 17501172





Orphanet Journal of Rare Diseases
Editorial
BioMed Central, CAMPUS, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 9 Número:
Páginas:
WOS Id: 000347116400001
ID de PubMed: 25433810
imagen Green Published, gold

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