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

<b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> = 0.013). EO cases presented a higher mortality rate (35.8%) than late-onset (LO) cases (7.1%) (<i>p</i> < 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) (<i>p</i> < 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. <b>Conclusions</b>: 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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Journal
Nutrients
Published
2025-03-28
DOI
https://doi.org/10.3390/nu17071173
Primary Topic
Metabolism and Genetic Disorders
Type
article
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article

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

Elena de Dios, Belén Pérez, Raquel Yahyaoui, Ana María Márquez Armenteros et al.
Nutrients
Metabolism and Genetic Disorders
article

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

Elena de Dios, Belén Pérez, Raquel Yahyaoui, Ana María Márquez Armenteros, Inmaculada Vives, Delia Barrio-Carreras, Javier de las Heras, Mónica Ruiz‐Pons, Leticia Ceberio-Hualde, Amaya Bélanger-Quintana, Ana Bergua, Pilar Quijada‐Fraile, Pedro Moreno, José David Andrade, Concepción Sierra Córcoles, Lucía Dougherty‐de Miguel, Ana Felipe‐Rucián, Patricia Correcher Medina, Sinziana Stanescu, Mónica García-Peris, Luis Peña Quintana, Silvia María Meavilla Olivas, Isidro Vitoria, Álvaro Martín‐Rivada, Paula Sánchez‐Pintos, María Luz Couce, Mercedes Murray Hurtado, Javier Blasco‐Alonso, Marcello Bellusci, Camila García‐Volpe, Elvira Cañedo Villarroya, Àngels García‐Cazorla, Ana Moráis‐López, Elena Martín‐Hernández, Montserrat Morales‐Conejo, Mireia del Toro, Ana Matas-García, Rafael López‐Urdiales, Elisenda Cortès‐Saladelafont, M. Monroy, David Gil, Mariela de los Santos, Patricia Pérez‐Mohand, María Martín‐Cazaña, M.C. García Jiménez, Mercedes Gil‐Campos, María Camprodón, Fernando Castellanos-Pinedo, Carlos Losilla Alcalde
article en

Abstract

<b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>p</i> = 0.013). EO cases presented a higher mortality rate (35.8%) than late-onset (LO) cases (7.1%) (<i>p</i> < 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) (<i>p</i> < 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. <b>Conclusions</b>: 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.

NutrientsVol. 17(7)
Universidad de Las Palmas de Gran Canaria (ES), Hospital Sant Joan de Déu Barcelona (ES), Hospital Universitario Insular de Gran Canaria (ES), Hospital Universitario de Canarias (ES), Hospital Universitario La Paz (ES), Bellvitge University Hospital (ES), Hospital Universitari i Politècnic La Fe (ES), Hospital Universitario Nuestra Señora de Candelaria (ES), BioCruces Health research Institute (ES), Instituto Maimónides de Investigación Biomédica de Córdoba (ES), Complejo Hospitalario Universitario de Santiago (ES), Hospital Universitario 12 De Octubre (ES), Hospital Regional Universitario de Málaga (ES), Centre for Biomedical Network Research on Rare Diseases (ES), Hospital Infantil Universitario Niño Jesús (ES), Hospital Universitario Miguel Servet (ES), Centro de Investigación Biomédica en Red (ES), Complejo Hospitalario de Jaén (ES), Hospital Universitario Reina Sofía (ES), Hospital Materno-Infantil (ES), Centro de Implantología Cirugía Oral y Maxilofacial (ES), Centro de Biología Molecular Severo Ochoa (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitario Virgen del Rocío (ES), Hospital Universitari Germans Trias i Pujol (ES), Hospital Universitario Ramón y Cajal (ES), Hospital Virgen del Puerto (ES), Instituto de Investigación Biomédica de Málaga (ES)
Albert Einstein College of Medicine, Yeshiva University
Openalex Percentile: Top 92%
Metabolism and Genetic Disorders
DOIOpen Access PDFOpenAlex
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