A national approach to rapid genomic diagnosis in acute pediatrics

Abstract

Background/Aim: Implementation of rapid genomic testing in neonatal and pediatric intensive care units (NICUs/PICUs) is gathering momentum, and requires the development of systems capable of consistent delivery across multiple sites. Methods: We developed a rapid genomic diagnosis program involving 10 Australian hospitals and two laboratories with the aim of providing test results in <5 days for acutely unwell pediatric patients with suspected monogenic disorders. Rapid exome sequencing (rES) was performed as trios when possible, and analysis utilized multidisciplinary expertise. Experience was shared between clinical sites, laboratories, and professional groups to enable collective learning. Results: The program considered 123 patients for rES over 10 months, and approved 114 (93%). Five families declined testing (4.4%), and nine (7.9%) were withdrawn due to change in clinical circumstances. Of 100 patients tested, 53 received a diagnosis. Twelve of the diagnoses (23%) were made using approaches augmenting standard ES analysis: mitochondrial genome sequencing, ES-based copy number analysis, matchmaking of emerging genes, reverse phenotyping and RNA analysis. Median time from hospital admission to consent was 6 days (range 0-64 days); median time from sample receipt to clinical ES report was 3 days (range 2-7 days). The total cost of testing was AU $1,123,000 (AU$11,230 per case). Changesin management following a result occurred in 77% of diagnosed patients and 10% of undiag-nosed patients. Conclusions: We demonstrate the feasibility of a national, highly integrated clinical-laboratory approach to rapid genomic diagnosis, which delivers results within a timeframe relevant to acute pediatrics, while optimizing clinical utility and resource allocation.L6298896572019-11-25 <br />