BACKGROUND: Lysosomal acid lipase deficiency is an autosomal recessive metabolic 
disease with a wide range of severity from Wolman Disease to Cholesterol Ester 
Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has 
been approved by drug agencies for treatment of this lysosomal disease. 
Ezetimibe is an azetidine derivative which blocks Niemann Pick C1-Like 1 
Protein; as its consequence, plasmatic concentration of low density lipoproteins 
and other apoB-containing lipoproteins, that are the substrate of lysosomal acid 
lipase, are decreased. Furthermore, ezetimibe acts by blocking inflammasome 
activation which is the cause of liver fibrosis in steatohepatitis and in 
lysosomal storage diseases.
RESULTS: Two patients with Cholesterol Ester Storage Disease were treated with 
ezetimibe for 9 years and a third patients for 10 years. Treatment was 
supplemented with low dose of atorvastatin in the first two patients during the 
last 6 years. All patients showed a significant reduction of alanine 
aminotransferase, cholesterol and triglyceride. Furthermore, no progression of 
liver fibrosis was demonstrated.
CONCLUSION: In this observational case series, ezetimibe is effective, safe, and 
sustainable treatment for lysosomal acid lipase deficiency. Further studies are 
warranted to demonstrate that ezetimibe is an alternative therapy to enzyme 
replacement therapy.