Pulmonary involvement in siblings with Gaucher disease type III

Area of Science:

• Genetics and rare diseases
• Pulmonology
• Pediatric medicine

Background:

• Pulmonary involvement in Gaucher disease (GD) is uncommon but linked to L444P mutations in the GBA gene.
• GD type III typically presents with systemic symptoms, with pulmonary disease being a less frequent manifestation.

Observation:

• This report details two sisters with GD type III and pulmonary involvement.
• One sister experienced fatal respiratory failure due to GD complications.
• The other, homozygous for the L444P mutation, developed asymptomatic pulmonary disease after enzyme replacement therapy (ERT).

Findings:

• Homozygosity for the L444P mutation in the GBA gene is associated with a high risk of primary pulmonary disease in GD.
• Pulmonary disease in GD type III, particularly in L444P homozygotes, requires thorough investigation using HRCT, BAL cytology, and lung biopsy.
• The efficacy of ERT for pulmonary manifestations in these patients is not yet clearly defined.

Implications:

• Primary lung disease should be considered a significant clinical feature in children with GD who are homoallelic for the L444P mutation.
• Further research is needed to understand the long-term outcomes and optimal management strategies for pulmonary involvement in GD.
• This case highlights the importance of comprehensive screening and monitoring for pulmonary complications in at-risk GD populations.