Background: 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. Methods: 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. Results: 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, 5 had likely pathogenic variants. In 3 cases with diagnostic genetic results, there was a modification to clinical care attributable to information provided by exome sequencing. Conclusions: 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.

Osteocraniostenosis (OCS, OMIM #602361) is a severe, usually lethal condition characterized by gracile bones with thin diaphyses, a cloverleaf-shaped skull and splenic hypo/aplasia. The condition is caused by heterozygous mutations in the FAM111A gene and is allelic to the non-lethal, dominant disorder Kenny‐Caffey syndrome (KCS, OMIM #127000). Here we report two new cases of OCS, including one with a detailed pathological examination. We review the main diagnostic signs of OCS both before and after birth based on our observations and on the literature. We then review the current knowledge on the mutational spectrum of FAM111A associated with either OCS or KCS, including three novel variants, both from one of the OCS fetuses described here, and from further cases diagnosed at our centers. This report refines the previous knowledge on OCS and expands the mutational spectrum that results in either OCS or KCS.

Defects in peroxisomal transport interferes with β-oxidation of very long chain fatty acids (VLCFAs). Subsequent VLCFA accumulation triggers a cascade of events that eventually leads to adrenoleukodystrophy (ALD). c Attention-deficit/hyperactivity disorder (ADHD) can be one of the early manifestations of childhood cerebral ALD (CCALD). c Patients with adrenomyeloneuropathy (AMN) may have signs of occult self-halted CCALD on MRI, which can help point to a diagnosis of AMN.