# Case Report: Diagnosis of Gaucher disease in a toddler with acute respiratory failure

## TL;DR

A toddler with acute respiratory failure was diagnosed with Gaucher disease through genetic testing and enzyme activity analysis.

## Contribution

The paper reports a new likely pathogenic GBA1 variant and an unusual clinical presentation of Gaucher disease.

## Key findings

- Rapid whole genome sequencing identified a novel likely pathogenic variant in the GBA1 gene.
- Low leukocyte acid β-glucosidase activity confirmed the diagnosis of Gaucher disease.
- The case highlights the importance of multidisciplinary approaches and rapid genetic testing in diagnosing rare diseases.

## Abstract

A 22-month-old male infant presented with cyanosis and stridor after a trivial fall and then developed acute respiratory distress. The respiratory status of the patient 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.L483P, and a paternally inherited novel likely pathogenic variant, p.P358l. The diagnosis of Gaucher disease was confirmed with low leukocyte acid β-glucosidase 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 a condition of 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.