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

(This article belongs to the Special Issue Nutritional Treatment and Screening for Inherited Metabolic Diseases).

Detalles Bibliográficos
Autores: Martín-Hernández, Elena, Bellusci, Marcello, Pérez-Mohand, Patricia, Correcher Medina, Patricia, Blasco-Alonso, Javier, Morais-López, Ana, de las Heras, Javier, Meavilla Olivas, Silvia María, Dougherty-de Miguel, Lucy, Couce, María Luz, Villarroya, Elvira Cañedo, García Jiménez, María Concepción, Moreno-Lozano, Pedro Juan, Vives, Inmaculada, Gil-Campos, Mercedes, Stanescu, Sinziana, Ceberio-Hualde, Leticia, Camprodón, María, Cortès-Saladelafont, Elisenda, López-Urdiales, Rafael, Murray Hurtado, Mercedes, Márquez Armenteros, Ana María, Sierra Córcoles, Concha, Peña-Quintana, Luis, Ruiz-Pons, Mónica, Alcalde, Carlos, Castellanos-Pinedo, Fernando, Dios, Elena, Barrio-Carreras, Delia, Martín-Cazaña, María, García-Peris, Mónica, Andrade, José David, García-Volpe, Camila, de los Santos, Mariela, García-Cazorla, Angels, del Toro, Mireia, Felipe-Rucián, Ana, Comino Monroy, María José, Sánchez-Pintos, Paula, Matas, Ana, Gil Ortega, David, Martín-Rivada, Álvaro, Bergua, Ana, Belanger-Quintana, Amaya, Vitoria, Isidro, Yahyaoui, Raquel, Pérez, Belén, Morales-Conejo, Montserrat, Quijada-Fraile, Pilar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/385752
Acceso en línea:http://hdl.handle.net/10261/385752
Access Level:acceso abierto
Palabra clave:Urea cycle disorders (UCDs)
Arginase 1 (ARG1)
Argininosuccinate lyase (ASL)
Argininosuccinate synthetase (ASS1)
Carbonic anhydrase VA (CA-VA)
Citrin
Carbamoylphosphate synthetase (CPS1)
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)
N-acetylglutamate synthase (NAGS)
Ornithine/citrulline antiporter (ORNT)
Ornithine transcarbamylase (OTC)
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oai_identifier_str oai:digital.csic.es:10261/385752
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
title Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
spellingShingle Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
Martín-Hernández, Elena
Urea cycle disorders (UCDs)
Arginase 1 (ARG1)
Argininosuccinate lyase (ASL)
Argininosuccinate synthetase (ASS1)
Carbonic anhydrase VA (CA-VA)
Citrin
Carbamoylphosphate synthetase (CPS1)
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)
N-acetylglutamate synthase (NAGS)
Ornithine/citrulline antiporter (ORNT)
Ornithine transcarbamylase (OTC)
title_short Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
title_full Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
title_fullStr Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
title_full_unstemmed Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
title_sort Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish Registry
dc.creator.none.fl_str_mv Martín-Hernández, Elena
Bellusci, Marcello
Pérez-Mohand, Patricia
Correcher Medina, Patricia
Blasco-Alonso, Javier
Morais-López, Ana
de las Heras, Javier
Meavilla Olivas, Silvia María
Dougherty-de Miguel, Lucy
Couce, María Luz
Villarroya, Elvira Cañedo
García Jiménez, María Concepción
Moreno-Lozano, Pedro Juan
Vives, Inmaculada
Gil-Campos, Mercedes
Stanescu, Sinziana
Ceberio-Hualde, Leticia
Camprodón, María
Cortès-Saladelafont, Elisenda
López-Urdiales, Rafael
Murray Hurtado, Mercedes
Márquez Armenteros, Ana María
Sierra Córcoles, Concha
Peña-Quintana, Luis
Ruiz-Pons, Mónica
Alcalde, Carlos
Castellanos-Pinedo, Fernando
Dios, Elena
Barrio-Carreras, Delia
Martín-Cazaña, María
García-Peris, Mónica
Andrade, José David
García-Volpe, Camila
de los Santos, Mariela
García-Cazorla, Angels
del Toro, Mireia
Felipe-Rucián, Ana
Comino Monroy, María José
Sánchez-Pintos, Paula
Matas, Ana
Gil Ortega, David
Martín-Rivada, Álvaro
Bergua, Ana
Belanger-Quintana, Amaya
Vitoria, Isidro
Yahyaoui, Raquel
Pérez, Belén
Morales-Conejo, Montserrat
Quijada-Fraile, Pilar
author Martín-Hernández, Elena
author_facet Martín-Hernández, Elena
Bellusci, Marcello
Pérez-Mohand, Patricia
Correcher Medina, Patricia
Blasco-Alonso, Javier
Morais-López, Ana
de las Heras, Javier
Meavilla Olivas, Silvia María
Dougherty-de Miguel, Lucy
Couce, María Luz
Villarroya, Elvira Cañedo
García Jiménez, María Concepción
Moreno-Lozano, Pedro Juan
Vives, Inmaculada
Gil-Campos, Mercedes
Stanescu, Sinziana
Ceberio-Hualde, Leticia
Camprodón, María
Cortès-Saladelafont, Elisenda
López-Urdiales, Rafael
Murray Hurtado, Mercedes
Márquez Armenteros, Ana María
Sierra Córcoles, Concha
Peña-Quintana, Luis
Ruiz-Pons, Mónica
Alcalde, Carlos
Castellanos-Pinedo, Fernando
Dios, Elena
Barrio-Carreras, Delia
Martín-Cazaña, María
García-Peris, Mónica
Andrade, José David
García-Volpe, Camila
de los Santos, Mariela
García-Cazorla, Angels
del Toro, Mireia
Felipe-Rucián, Ana
Comino Monroy, María José
Sánchez-Pintos, Paula
Matas, Ana
Gil Ortega, David
Martín-Rivada, Álvaro
Bergua, Ana
Belanger-Quintana, Amaya
Vitoria, Isidro
Yahyaoui, Raquel
Pérez, Belén
Morales-Conejo, Montserrat
Quijada-Fraile, Pilar
author_role author
author2 Bellusci, Marcello
Pérez-Mohand, Patricia
Correcher Medina, Patricia
Blasco-Alonso, Javier
Morais-López, Ana
de las Heras, Javier
Meavilla Olivas, Silvia María
Dougherty-de Miguel, Lucy
Couce, María Luz
Villarroya, Elvira Cañedo
García Jiménez, María Concepción
Moreno-Lozano, Pedro Juan
Vives, Inmaculada
Gil-Campos, Mercedes
Stanescu, Sinziana
Ceberio-Hualde, Leticia
Camprodón, María
Cortès-Saladelafont, Elisenda
López-Urdiales, Rafael
Murray Hurtado, Mercedes
Márquez Armenteros, Ana María
Sierra Córcoles, Concha
Peña-Quintana, Luis
Ruiz-Pons, Mónica
Alcalde, Carlos
Castellanos-Pinedo, Fernando
Dios, Elena
Barrio-Carreras, Delia
Martín-Cazaña, María
García-Peris, Mónica
Andrade, José David
García-Volpe, Camila
de los Santos, Mariela
García-Cazorla, Angels
del Toro, Mireia
Felipe-Rucián, Ana
Comino Monroy, María José
Sánchez-Pintos, Paula
Matas, Ana
Gil Ortega, David
Martín-Rivada, Álvaro
Bergua, Ana
Belanger-Quintana, Amaya
Vitoria, Isidro
Yahyaoui, Raquel
Pérez, Belén
Morales-Conejo, Montserrat
Quijada-Fraile, Pilar
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dc.contributor.none.fl_str_mv Lucane Pharma
Immedica
Pérez, Belén [0000-0002-3190-1958]
dc.subject.none.fl_str_mv Urea cycle disorders (UCDs)
Arginase 1 (ARG1)
Argininosuccinate lyase (ASL)
Argininosuccinate synthetase (ASS1)
Carbonic anhydrase VA (CA-VA)
Citrin
Carbamoylphosphate synthetase (CPS1)
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)
N-acetylglutamate synthase (NAGS)
Ornithine/citrulline antiporter (ORNT)

Ornithine transcarbamylase (OTC)
topic Urea cycle disorders (UCDs)
Arginase 1 (ARG1)
Argininosuccinate lyase (ASL)
Argininosuccinate synthetase (ASS1)
Carbonic anhydrase VA (CA-VA)
Citrin
Carbamoylphosphate synthetase (CPS1)
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)
N-acetylglutamate synthase (NAGS)
Ornithine/citrulline antiporter (ORNT)
Ornithine transcarbamylase (OTC)
description (This article belongs to the Special Issue Nutritional Treatment and Screening for Inherited Metabolic Diseases).
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/385752
url http://hdl.handle.net/10261/385752
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/nu17071173
https://doi.org/10.3390/nu17071173
No
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422587266727936
spelling Understanding the Natural History and the Effects of Current Therapeutic Strategies on Urea Cycle Disorders: Insights from the UCD Spanish RegistryMartín-Hernández, ElenaBellusci, MarcelloPérez-Mohand, PatriciaCorrecher Medina, PatriciaBlasco-Alonso, JavierMorais-López, Anade las Heras, JavierMeavilla Olivas, Silvia MaríaDougherty-de Miguel, LucyCouce, María LuzVillarroya, Elvira CañedoGarcía Jiménez, María ConcepciónMoreno-Lozano, Pedro JuanVives, InmaculadaGil-Campos, MercedesStanescu, SinzianaCeberio-Hualde, LeticiaCamprodón, MaríaCortès-Saladelafont, ElisendaLópez-Urdiales, RafaelMurray Hurtado, MercedesMárquez Armenteros, Ana MaríaSierra Córcoles, ConchaPeña-Quintana, LuisRuiz-Pons, MónicaAlcalde, CarlosCastellanos-Pinedo, FernandoDios, ElenaBarrio-Carreras, DeliaMartín-Cazaña, MaríaGarcía-Peris, MónicaAndrade, José DavidGarcía-Volpe, Camilade los Santos, MarielaGarcía-Cazorla, Angelsdel Toro, MireiaFelipe-Rucián, AnaComino Monroy, María JoséSánchez-Pintos, PaulaMatas, AnaGil Ortega, DavidMartín-Rivada, ÁlvaroBergua, AnaBelanger-Quintana, AmayaVitoria, IsidroYahyaoui, RaquelPérez, BelénMorales-Conejo, MontserratQuijada-Fraile, PilarUrea cycle disorders (UCDs)Arginase 1 (ARG1)Argininosuccinate lyase (ASL)Argininosuccinate synthetase (ASS1)Carbonic anhydrase VA (CA-VA)CitrinCarbamoylphosphate synthetase (CPS1)Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH)N-acetylglutamate synthase (NAGS)Ornithine/citrulline antiporter (ORNT)Ornithine transcarbamylase (OTC)(This article belongs to the Special Issue Nutritional Treatment and Screening for Inherited Metabolic Diseases).<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.This research was partially funded by Lucane SL and Immedica Pharma Spain. Medical writing support was funded by Immedica Pharma Spain.Peer reviewedMultidisciplinary Digital Publishing InstituteLucane PharmaImmedicaPérez, Belén [0000-0002-3190-1958]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/385752reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.3390/nu17071173https://doi.org/10.3390/nu17071173Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3857522026-05-22T06:33:51Z
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