Lysosomes are intra-cellular organelles that are responsible for degrading and recycling
macromolecules. Lysosomal diseases (LDs) are a group of rare inherited diseases caused
by deleterious variants affecting genes that encode the lysosomal enzymes, their transporter
or their cofactor. Among LDs that are associated with lung involvement and/or interstitial
lung disease (ILD) acid sphingomyelinase deficiency [ASMD formerly called Niemann-Pick
A, AB and B diseases]) is the most common. An history of lower respiratory tract infections
and exertional dyspnoea are the most frequent respiratory manifestations. In ASMD,
ILD is frequent and is usually associated with spleen and/or liver enlargement, low
platelet count, and low level of high-density lipoprotein-cholesterol. A restrictive
lung functional pattern and a reduction in DLCO value are usually observed. Analysis
of bronchoalveolar lavage fluid and lung biopsy showing foamy cells can orientate
the diagnosis, based on the demonstration of an enzymatic deficiency in sphingomyelinase
in the blood, associated with biallelic pathogenic variants of the SMPD1 gene. An
enzyme replacement therapy (ERT), based on intravenous recombinant enzyme infusions
(olipudase alfa), is available from 2021 with very encouraging results both in pediatric
and adult patients affected with type B or AB. Olipudase alfa administration decreased
liver and spleen volume, increased DLCO value and improved radiological lung involvement.
Available enzyme replacement therapy supports an early diagnosis to implement therapy
before any irreversible organ damage
