Health Outcomes of Patients with Distal Urea Cycle Disorders Detected by Newborn Screening: Data from the Spanish National Registry
Raquel Yahyaoui, Pilar Quijada-Fraile, Javier Blasco-Alonso, Inmaculada Vives, David Gil Ortega, Maria-Luz Couce, Paula Sánchez-Pintos, M. Concepción García Jiménez, Silvia Meavilla Olivas, Camila García Volpe, Mariela de los Santos Mercedes, Ángels García-Cazorla, Ana Felipe-Rucián, Lucy Dougherty-de Miguel, Ana Morais López, Ana Bergua Martínez, José David Andrade Guerrero, Sinziana Stanescu, Amaya Belanger, Mercedes Gil-Campos, María José Comino Monroy, Marcello Bellusci, Patricia Pérez-Mohand, Delia Barrio-Carreras, Belén Pérez, Elena Martín-HernándezUrea 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.