Health Outcomes of Patients with Distal Urea Cycle Disorders Detected by Newborn Screening: Data from the Spanish National Registry

Urea cycle disorders (UCDs) are rare inherited metabolic diseases associated with toxic hyperammonemia, leading to severe neurological damage and early mortality. Early diagnosis of distal UCDs through newborn screening (NBS) enables presymptomatic intervention; however, comparative real-world outcome data remain limited. We conducted a retrospective, multicenter study using data from the Spanish UCD Registry to describe the clinical characteristics and compare health outcomes between patients diagnosed through NBS (n = 40) and those diagnosed after clinical presentation (n = 53). Patients identified by NBS showed a markedly more favorable clinical prognosis, with a mortality rate of 2.5% compared with 15.1% in the unscreened cohort, as well as significantly lower rates of neurological involvement, fewer hospital admissions due to metabolic decompensation, and a reduced need for liver transplantation. Screening also identified a high prevalence of argininosuccinate synthetase deficiency (ASS1D) cases with attenuated biochemical profiles, highlighting the relevance of sensitive screening cutoffs. These findings provide real-world evidence that presymptomatic diagnosis through NBS is associated with improved survival and long-term neurological outcomes in patients with distal UCDs.

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Journal
International Journal of Neonatal Screening
Published
2026-06-18
DOI
https://doi.org/10.3390/ijns12020044
Primary Topic
Metabolism and Genetic Disorders
Type
article
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article

Health Outcomes of Patients with Distal Urea Cycle Disorders Detected by Newborn Screening: Data from the Spanish National Registry

Belén Pérez, Raquel Yahyaoui, Inmaculada Vives, Delia Barrio-Carreras et al.
International Journal of Neonatal Screening
Metabolism and Genetic Disorders
article

Health Outcomes of Patients with Distal Urea Cycle Disorders Detected by Newborn Screening: Data from the Spanish National Registry

Belén Pérez, Raquel Yahyaoui, Inmaculada Vives, Delia Barrio-Carreras, Amaya Bélanger-Quintana, Pilar Quijada‐Fraile, Lucía Dougherty‐de Miguel, Silvia Meavilla Olivas, Ana Felipe‐Rucián, Sinziana Stanescu, Paula Sánchez‐Pintos, María Luz Couce, Javier Blasco‐Alonso, Marcello Bellusci, Àngels García‐Cazorla, Ana Moráis‐López, David Gil, Ana Bergua Martínez, Patricia Pérez‐Mohand, Mercedes Gil‐Campos, Camila García Volpe, M. Concepción García García Jiménez, José David Andrade Andrade Guerrero, Elena Martín-Hernández, Mariela de los Santos Mercedes, María José Comino Comino Monroy
article en

Abstract

Urea cycle disorders (UCDs) are rare inherited metabolic diseases associated with toxic hyperammonemia, leading to severe neurological damage and early mortality. Early diagnosis of distal UCDs through newborn screening (NBS) enables presymptomatic intervention; however, comparative real-world outcome data remain limited. We conducted a retrospective, multicenter study using data from the Spanish UCD Registry to describe the clinical characteristics and compare health outcomes between patients diagnosed through NBS (n = 40) and those diagnosed after clinical presentation (n = 53). Patients identified by NBS showed a markedly more favorable clinical prognosis, with a mortality rate of 2.5% compared with 15.1% in the unscreened cohort, as well as significantly lower rates of neurological involvement, fewer hospital admissions due to metabolic decompensation, and a reduced need for liver transplantation. Screening also identified a high prevalence of argininosuccinate synthetase deficiency (ASS1D) cases with attenuated biochemical profiles, highlighting the relevance of sensitive screening cutoffs. These findings provide real-world evidence that presymptomatic diagnosis through NBS is associated with improved survival and long-term neurological outcomes in patients with distal UCDs.

International Journal of Neonatal ScreeningVol. 12(2)
Hospital Sant Joan de Déu Barcelona (ES), Hospital Universitario La Paz (ES), Research Institute Hospital 12 de Octubre (ES), Hospital Universitario 12 De Octubre (ES), Vall d'Hebron Institut de Recerca (ES), Hospital Regional Universitario de Málaga (ES), Hospital Universitario Miguel Servet (ES), Hospital Universitario Reina Sofía (ES), Vall d'Hebron Hospital Universitari (ES), Hospital Universitario Virgen de la Arrixaca (ES), Hospital Universitario Ramón y Cajal (ES), Hospital Provincial de Conxo (ES), Universidad Autónoma de Madrid (ES), Universidad de Málaga (ES)
Good health and well-being
Openalex Percentile: Top 8%
Metabolism and Genetic Disorders
DOIOpen Access PDFOpenAlex
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