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cc-by (c) Martín Hernández et al., 2025
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/221674

Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry

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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 mol/L (IQR 410-1793) than in survivors at 294 mu mol/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.

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MARTÍN HERNÁNDEZ, Elena, BELLUSCI, Marcello, PÉREZ MOHAND, Patricia, CORRECHER MEDINA, Patricia, BLASCO ALONSO, Javier, MORAIS LÓPEZ, Ana, HERAS MONTERO, Javier de las, MEAVILLA OLIVAS, Silvia maria, DOUGHERTY DE MIGUEL, Lucy, COUCE, María luz, CAÑEDO VILLARROYA, Elvira, GARCÍA JIMÉNEZ, María concepción, MORENO LOZANO, Pedro juan, VIVES, Inmaculada, GIL CAMPOS, Mercedes, STANESCU, Sinziana, CEBERIO HUALDE, Leticia, CAMPRODÓN GÓMEZ, Maria, CORTÈS SALADELAFONT, Elisenda, LÓPEZ URDIALES, Rafael, MURRAY HURTADO, Mercedes, MÁRQUEZ ARMENTEROS, Ana maria, SIERRA CÓRCOLES, Concha, PEÑA QUINTANA, Luis, RUIZ PONS, Mónica, ALCALDE MARTÍN, Carlos, CASTELLANOS PINEDO, Fernando, DIOS, Elena, BARRIO CARRERAS, Delia, MARTÍN CAZAÑA, María, GARCÍA PERIS, Mónica, ANDRADE, José david, GARCÍA VOLPE, Camila, SANTOS MERCEDES, Mariela mercedes de los, GARCÍA CAZORLA, Àngels, TORO, Mireia del, FELIPE RUCIAN, Ana, COMINO MONROY, Maria jose, SÁNCHEZ PINTOS, Paula, MATAS GARCÍA, Ana, GIL ORTEGA, David, MARTÍN RIVADA, Álvaro, BERGUA MARTÍNEZ, Ana, BELANGER QUINTANA, Amaya, VITORIA MIÑANA, Isidro, YAHYAOUI, Raquel, PÉREZ GÓNZALEZ, María belen, MORALES CONEJO, Montserrat, QUIJADA FRAILE, Pilar. Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry. _Nutrients_. 2025. Vol. 17, núm. 7. [consulta: 5 de maig de 2026]. ISSN: 2072-6643. [Disponible a: https://hdl.handle.net/2445/221674]

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