Interstitial lung disease in lysosomal storage disorders

Area of Science:

• Biochemistry
• Genetics
• Pulmonology

Background:

• Lysosomes are vital organelles for macromolecule degradation and recycling.
• Lysosomal storage diseases (LSDs) arise from genetic mutations impacting lysosomal enzyme function.
• Three LSDs—Gaucher disease (GD), Niemann-Pick disease (ASMD), and Fabry disease (FD)—are linked to lung involvement, including interstitial lung disease (ILD).

Purpose of the Study:

• To review the pulmonary manifestations of Gaucher disease, Niemann-Pick disease, and Fabry disease.
• To highlight the importance of early diagnosis and treatment for LSDs with lung involvement.
• To discuss the role of enzyme replacement therapy (ERT) in managing these conditions.

Main Methods:

• Review of literature on LSDs with pulmonary manifestations.
• Analysis of diagnostic findings such as bronchoalveolar lavage fluid and lung biopsy.
• Evaluation of treatment outcomes, particularly ERT, for affected patients.

Main Results:

• Foamy cells observed in bronchoalveolar lavage fluid and lung biopsies are indicative of GD and ASMD.
• ILD is a rare but serious complication of GD.
• ILD is frequent in ASMD, often accompanied by splenomegaly, thrombocytopenia, and low HDL-cholesterol; ERT with olipudase alfa shows promise.
• FD commonly presents with COPD-like symptoms and heart failure-related dyspnea.
• Early ERT has significantly improved outcomes, preventing pulmonary failure in GD.

Conclusions:

• Early detection and intervention with ERT are critical for mitigating irreversible organ damage in GD, ASMD, and FD.
• Prompt initiation of ERT can prevent or partially reverse organ failure in these LSDs.
• Understanding the specific pulmonary presentations of these LSDs aids in timely diagnosis and management.