Introduction Adult cholesteryl ester storage disease (CESD) is characterized by an autosomal-recessive
deficiency of lysosomal acid lipase (LAL), which leads to accumulation of cholesteryl
esters/triglycerides in macrophages with consecutive hepatosplenic involvement. In
contrast to infantile Wolman disease, CESD follows a more benign clinical course.
Sebelipase-α (Kanuma®, Alexion) is a recombinant form of LAL approved in 2015 as
enzyme replacement therapy (ERT) for CESD.
Methods Single-center retrospective study of CESD patients between 1999-2021.
Results Three patients were diagnosed with CESD. Patient #1 was a 36-year-old woman with
hepatosplenomegaly and anemia, suspected for Gaucher´s disease. Palpebral xanthelasmata,
enlarged supraclavicular lymph nodes and severe splenomegaly were noted. LDL/HDL was
211/25 mg/dl. Bone marrow aspirates revealed sea-blue histiocytes. Plasma chitotriosidase
activity (CTA) was 827 nmol/ml/h (Ref. 20-100) and fibroblasts exhibited a 15-fold
increase of cholesteryl esters. LAL activity was reduced and mutational analysis confirmed
the diagnosis of CESD.
Pats. #2/#3 were siblings aged 30/32 with severe hepatomegaly and xanthelasmata. Total
cholesterol was 480/500 mg/dl, livers were massively enlarged, with only slight splenomegaly.
CTA was elevated 2-3 fold in both cases. Therapies with statins/colestyramin/colesevelam
and ERT with sebelipase alpha decreased liver volume.
Conclusion In patients with liver steatosis, hepatosplenomegaly and elevated LDL/HDL ratio/hypercholesterolemia,
CESD should be considered. Sebelipase-α improves visceral manifestations in this lysosomal
storage disease.
