BACKGROUND: Acid sphingomyelinase deficiency (ASMD), [Niemann-Pick Disease Types 
A and B (NPD A and B)], is an inherited metabolic disorder resulting from 
deficiency of the lysosomal enzyme acid sphingomyelinase. Accumulation of 
sphingomyelin in hepatocytes, reticuloendothelial cells, and in some cases 
neurons, results in a progressive multisystem disease that encompasses a broad 
clinical spectrum of neurological and visceral involvement, including: infantile 
neurovisceral ASMD (NPD A) that is uniformly fatal by 3years of age; chronic 
neurovisceral ASMD (intermediate NPD A/B; NPD B variant) that has later symptom 
onset and slower neurological and visceral disease progression; and chronic 
visceral ASMD (NPD B) that lacks neurological symptoms but has significant 
disease-related morbidities in multiple organ systems. The purpose of this study 
was to characterize disease-related morbidities and causes of death in patients 
with the chronic visceral and chronic neurovisceral forms of ASMD.
METHODS: Data for 85 patients who had died or received liver transplant were 
collected by treating physicians (n=27), or abstracted from previously published 
case studies (n=58). Ages at symptom onset, diagnosis, and death; cause of 
death; organ involvement, and morbidity were analyzed.
RESULTS: Common disease-related morbidities included splenomegaly (96.6%), 
hepatomegaly (91.4%), liver dysfunction (82.6%), and pulmonary disease (75.0%). 
The overall leading causes of death were respiratory failure and liver failure 
(27.7% each) irrespective of age. For patients with chronic neurovisceral ASMD 
(31.8%), progression of neurodegenerative disease was a leading cause of death 
along with respiratory disease (both 23.1%) and liver disease (19.2%). Patients 
with chronic neurovisceral disease died at younger ages than those with chronic 
visceral disease (median age at death 8 vs. 23.5years).
CONCLUSIONS: The analysis emphasizes that treatment goals for patients with 
chronic visceral and chronic neurovisceral ASMD should include reducing 
splenomegaly and improving liver function and respiratory status, with the 
ultimate goal of decreasing serious morbidity and mortality.