Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an 
autosomal recessive genetic disorder caused by different SMPD1 mutations. 
Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A 
(NPD A) and B (NPD B). NPD A is associated with a uniformly devastating disease 
course, with rapidly progressing psychomotor degeneration, leading to death 
typically by the age of 3 years, most often from respiratory failure. In 
contrast, the clinical phenotype and life expectancy of patients with NPD B may 
vary widely. Almost all patients have hepatosplenomegaly and an atherogenic 
lipid profile, and most patients have interstitial lung disease with progressive 
impairment of pulmonary function and hematologic abnormalities including 
cytopenias. Other common clinical manifestations include liver dysfunction, 
heart disease, skeletal abnormalities and growth delays. Some patients with ASMD 
who survive beyond early childhood have intermediate phenotypes (variant NPD B) 
characterized by combinations of non-neurologic and mild to severe neurologic 
symptoms. The physical and psychosocial burden of illness in patients with NPD B 
is substantial. Common symptoms include shortness of breath, joint or limb pain, 
abdominal pain, bleeding and bruising. The disease often leads to chronic 
fatigue, limited physical or social activity and difficulties in performing 
daily activities or work. Many patients die before or in early adulthood, often 
from pneumonia/respiratory failure or liver failure. Available treatments are 
limited to symptom management and supportive care. An enzyme replacement therapy 
currently in clinical development is expected to be the first treatment 
addressing the underlying pathology of the disease. Early diagnosis and 
appropriate management are essential for reducing the risk of complications. 
While knowledge about ASMD is evolving, more evidence about ASMD and the natural 
history across the disease spectrum is needed, to improve disease recognition, 
timely diagnosis and appropriate disease management.