Diagnosis of Gaucher Disease in Toddler with Acute Respiratory Failure: A Case Report

Sarah Householder ¹ Ruchit Nagar ¹ Nisarg Shah ² Jodi Forward ¹ Sean Bickerton ¹ Pramod Mistry ² E. Vincent Faustino ^2*

• ¹ Yale-New Haven Hospital, New Haven, United States
• ² School of Medicine, Yale University, New Haven, Connecticut, United States

A 22-month-old male presented with cyanosis and stridor after a trivial fall, then developed acute respiratory distress. The patient's respiratory status progressed rapidly to severe acute respiratory distress syndrome. Additional findings of hypersplenism prompted a comprehensive multidisciplinary approach and consideration of an inborn error of metabolism. Rapid whole genome sequence showed a compound heterozygote mutation in the GBA1 gene involving a maternally inherited known pathogenic variant, p.L484P, and a paternally inherited novel likely pathogenic variant, p.P358L. The diagnosis of Gaucher disease was confirmed with low leukocyte acid βglucosidase activity and the patient received recombinant macrophage-targeted enzyme replacement therapy. The patient eventually recovered but subsequent work-up demonstrated severe bulbar dysfunction with evidence of aspiration. Two months after discharge, the patient arrived at the hospital in cardiac arrest after a suspected aspiration event associated with hemoptysis. This case illustrates a previously undescribed presentation of Gaucher disease and a new likely pathogenic genetic variant for Gaucher disease. It highlights the role of a multidisciplinary approach, including rapid whole genome sequencing, to establish timely diagnosis and provide appropriate therapy for Gaucher disease.