Trio-Based Whole-Genome Sequencing for Critically Ill Pediatric Patients in Korea

Abstract

This study aimed to implement genome sequencing using an automated pipeline for critically ill pediatric patients within a real-world healthcare system. Twenty patients under 36 months of age, admitted to the NICU/PICU or suspected of having rapidly progressive genetic disorders, were enrolled. Trio-based genome sequencing was performed using an optimized processing pipeline, which automatically performed mapping, variant calling, annotation, and in silico pathogenicity assessment. Among 20 enrolled patients, 11 (55%) were from the NICU, and 16 (80%) presented with neurological manifestations as their chief complaint. The median time from symptom onset to study enrollment was 73 days for 18 patients referred from other hospitals and less than a week for 2 in-hospital patients. The median turnaround time (TAT) for rWGS was 10 days, with the shortest being 5 days. A definite or presumed genetic diagnosis was made in 11 patients (55%), including 10 of 16 with neurological symptoms (62.5%) and 1 of 4 with non-neurologic symptoms (25%). Management plans were modified for 8 of the 11 patients (72.7%), including medication changes, diet modifications, and preimplantation genetic testing for future pregnancies. This study highlights the feasibility and clinical utility of WGS in critically ill pediatric patients in Korea, demonstrating a high diagnostic yield and significant impact on patient management, particularly among those presenting with neurologic symptoms. Establishing a nationwide fast-track system and providing detailed testing indications are required for effective implementation. Further automation and resource optimization could reduce the TAT and improve the efficacy of rWGS in critical care settings.