Evaluating Genomic Testing in Pediatric Inborn Errors of Immunity: An Optimal Model of Care

While genomic testing is integral to the management of pediatric inborn errors of immunity (IEI), few studies have examined strategies to support its optimal integration into routine healthcare. Thus, this study aimed to: (i) describe a pediatric IEI cohort and genomic testing practices, and (ii) assess the impact of implementing a multidisciplinary genomic model of care (MoC) on service outcomes.

A comprehensive chart audit was conducted for patients (≤ 18years) who received IEI genomic testing in Queensland, Australia, from 2017 to 2025. Descriptive analyses captured demographics, clinical characteristics, genomic testing and results, and management outcomes. Inferential analyses assessed changes in genomic practices pre-MoC (< 2021) and post-MoC (≥ 2021).

322 patients met eligibility criteria (n = 481 genomic tests). Diagnostic yield (mean:26.7%) varied by testing indication, with the highest rate among phagocytic defects (n = 4/4;100%) and severe combined immunodeficiency (n = 8/10;80.0%). Very early-onset inflammatory bowel disease had the lowest diagnostic yield (n = 3/68;4.4%), prompting local changes to testing criteria. Among patients with an IEI molecular diagnosis (n = 79), 89.9% received a management change recommendation. Genomic testing was widely used pre-MoC (n = 259 genomic tests). All outcomes significantly improved from pre-MoC to post-MoC (p < 0.05, chi-square test): duplicate testing eliminated (13.5% to 0.0%); variants of uncertain significance reduced (37.7% to 7.1%); informed consent documentation improved (70.5% to 88.4%); and diagnostic yield increased (14.5% to 27.4%).

Implementing a multidisciplinary genomic MoC in pediatric IEI improved clinical and health service outcomes. Building on these findings, this study offers practical recommendations for integrating genomic testing into routine pediatric IEI practice, to enhance diagnostic pathways and health service performance.