Sistema de Salut de Catalunya
Institut Català de la Salut
[Martín-Hernández E, Bellusci M, Pérez-Mohand P] Unidad de Enfermedades Mitocondriales-Metabólicas Hereditarias, Hospital Universitario 12 de Octubre, Instituto de Investigación Imas12, MetabERN, CIBERER, Madrid, Spain. [Correcher Medina P] Unidad de Nutrición y Metabolopatías, Hospital Universitario La Fé, Valencia, Spain. [Blasco-Alonso J] Unidad de Gastroenterología, Hepatología y Nutrición Pediátrica, Laboratorio de Bioquímica, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Regional Universitario de Málaga, Málaga, Spain. [Morais-López A] Unidad de Nutrición Infantil y Enfermedades Metabólicas, Hospital Universitario La Paz, Madrid, Spain. [Dougherty-de Miguel L, Camprodón M, del Toro M, Felipe-Rucián A] Unitat de Malalties Metabòliques Hereditàries, Vall d’Hebron Hospital Universitari, Barcelona, Spain. MetabERN, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-05-27T06:54:46Z
2025-05-27T06:54:46Z
2025-04
N-acetylglutamate synthase; Arginase 1; Urea cycle disorders
N-acetilglutamat sintasa; Arginasa 1; Trastorns del cicle de la urea
N-acetilglutamato sintasa; Arginasa 1; Trastornos del ciclo de la urea
Background/Objectives: The present study updates the Spanish registry of patients with urea cycle disorders (UCD), originally established in 2013, to provide comprehensive epidemiological data and evaluate the impact of therapeutic strategies and newborn screening (NBS) on clinical outcomes. Methods: This retrospective, multicenter study focuses on 255 Spanish UCD patients. It includes all living and deceased cases up to February 2024, analyzing demographic, clinical, and biochemical variables. Results: The incidence of UCD in Spain over the past decade was 1:36,063 births. The most common defects were ornithine transcarbamylase deficiency (OTCD) and argininosuccinate synthetase deficiency. Early-onset (EO) cases comprised 32.7%, and 10.6% were diagnosed through NBS. Global mortality was 14.9%, higher in carbamoylphosphate synthetase 1 deficiency (36.8%) and male OTCD patients (32.1%) compared to other defects (p = 0.013). EO cases presented a higher mortality rate (35.8%) than late-onset (LO) cases (7.1%) (p < 0.0001). The median ammonia level in deceased patients was higher at 1058 µmol/L (IQR 410–1793) than in survivors at 294 µmol/L (IQR 71–494) (p < 0.0001). Diagnosis through NBS improved survival and reduced neurological impairment compared to symptomatic diagnosis. Neurological impairment occurred in 44% of patients, with worse neurological outcomes observed in patients with argininosuccinate lyase deficiency, arginase 1 deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria, EO presentations, pre-2014 diagnosis, and patients with higher levels of ammonia at diagnosis. Among transplanted patients (20.6%), survival was 95.2%, with no significant neurological differences compared to non-transplanted patients. Conclusions: This updated analysis highlights the positive impact of NBS and advanced treatments on mortality and neurologic outcomes. Persistent neurological challenges underscore the need for further therapeutic strategies.
This research was partially funded by Lucane SL and Immedica Pharma Spain. Medical writing support was funded by Immedica Pharma Spain.
Article
Published version
English
Metabolisme, Errors congènits del - Tractament; Metabolisme, Errors congènits del - Diagnòstic; Cribatge (Medicina); Registres hospitalaris; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Neonatal Screening; DISEASES::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Amino Acid Metabolism, Inborn Errors::Congenital, Hereditary, and Neonatal Diseases and Abnormalities::Genetic Diseases, Inborn::Metabolism, Inborn Errors::Urea Cycle Disorders, Inborn; Other subheadings::Other subheadings::/therapy; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Epidemiologic Methods::Data Collection::Registries; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::técnicas y procedimientos diagnósticos::técnicas de laboratorio clínico::cribado neonatal; ENFERMEDADES::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::alteraciones congénitas del metabolismo de los aminoácidos::enfermedades y anomalías neonatales congénitas y hereditarias::enfermedades genéticas congénitas::alteraciones congénitas del metabolismo::trastornos congénitos del ciclo de la urea; Otros calificadores::Otros calificadores::/terapia; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::métodos epidemiológicos::recopilación de datos::registros
MDPI
Nutrients;17(7)
https://doi.org/10.3390/nu17071173
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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