Rapid exome sequencing in PICU patients with new-onset metabolic or neurological disorders

Genomic assessment previously took months to result and was unable to impact clinical care in the pediatric intensive care unit (PICU). The advent of rapid exome sequencing potentially changes this. We investigated the impact of rapid exome sequencing in a pilot study on pediatric patients admitted to a single PICU with new-onset metabolic/neurologic disease.

Rapid exome sequencing (7 days to verbal result) was performed on (n = 10) PICU patients age < 6 years admitted with new-onset metabolic/neurologic disease. The primary outcome of interest was inpatient LOS, which served as a proxy for inpatient cost.

A significant reduction in median LOS was identified when comparing PICU patients who underwent rapid exome sequencing to historical controls. From those patients who underwent rapid sequencing, five had likely pathogenic variants. In three cases with diagnostic genetic results, there was a modification to clinical care attributable to information provided by exome sequencing.

This pilot study demonstrates that rapid exome sequencing is feasible to do in the PICU, that genetic results can be returned quickly enough to impact critical care decision-making and management. In a select population of PICU patients, this technology may contribute to a decrease in hospital length of stay.

Ten prospectively enrolled PICU patients with defined clinical criteria and their parents underwent rapid exome sequencing. Fifty percent received a genetic diagnosis, and medical management was affected for 60% of those patients. Median hospital LOS was significantly decreased in this selective subset of PICU patients. Genetic disorders and congenital anomalies are a leading cause of pediatric mortality. Genomic assessment previously took weeks to months for results and was therefore unable to acutely impact clinical care in the pediatric intensive care unit (PICU). The recent advent of rapid exome sequencing changes this in selected patients. Rapid exome sequencing is feasible to do in a PICU. Genetic results can be returned quickly enough to impact critical care decision-making. When done in a carefully selected subset of pediatric patients, rapid exome sequencing can potentially decrease hospital LOS.