Rapid Diagnosis using Rapid Exome Sequencing for Children with Severe Acute Encephalopathy – a Case Series
2Metabolic Unit, Ruth Children’s Hospital
3Pediatric Neurology Unit, Ruth Children’s Hospital
4Pediatric Intensive Care Unit, Ruth Children’s Hospital
Introduction The increasing accessibility and quick turnaround time of next generation sequencing NGS is quickly transforming NGS into a powerful diagnostic tool even in critical care situations such as acute encephalopathy\encephalitis
Here, we describe a brief series of patients hospitalized with acute encephalopathy initially suspected to be infectious or inflammatory origin subsequently diagnosed with a monogenic disorder. Rapid and timely diagnosis informed clinical decisions in these cases
Methods: WES was performed during initial hospitalization for three unrelated patients with severe acute encephalopathy referred by the pediatric intensive care unit (PICU) team. All patients were previously healthy, 18- 36 months old with a history of consanguinity. One patient presenting with acute necrotizing encephalopathy (ANEC) had a sister who presented with ANEC one year prior.
Results: WES was diagnostic in all three cases. One patient had pathogenic variants in MOCS2, associated with late onset Molybdenum cofactor deficiency B. A second patient harbored likely pathogenic variants in NDUFS8 associated with Leigh disease. Surprisingly, the initial work-up and brain imaging was not suggestive. Finally, a likely pathogenic homozygous variant in the DBR1 gene was identified in the patients presenting with ANEC
Discussion and conclusion: As this case series demonstrates use of WES is shifting the paradigm of diagnostics even in critical care situations and should be considered in many situations early on during hospitalization. Timely and urgent use of NGS can provide rapid diagnosis preventing extensive and expensive work up while directing initial treatment as well as informing decisions regarding long term care.