Lysosomal acid lipase deficiency: The forgotten link between liver and cardiovascular disease

Abstract

Lysosomal acid lipase-deficiency (LAL-D) is a rare and systemic condition, secondary to lipase A gene mutations, responsible for lysosomal accumulation of cholesteryl esters and triglycerides in many tissues. It is a very heterogeneous disease in terms of the age of onset, severity, and the type of clinical and radiological manifestations. Dyslipidemia, hepatomegaly, and hepatosteatosis with increased levels of transaminases are the most common features. In association with liver dysfunction and evolution to cirrhosis, there is an increased risk of premature atherosclerosis and cardiovascular disorders, secondary to a generalized alteration of lipid profile and lipoprotein dysfunction associated with LAL-D. Therefore, we provide an update on the frequently under-recognized LAL-D, focusing on the late-onset form: Cholesteryl ester storage disease.

Keywords: Cholesteryl ester storage disease; Lysosomal acid lipase deficiency; Dyslipidemia; Non-alcoholic fatty liver disease; Lipase A

Core Tip: Lysosomal acid lipase deficiency is a rare disease caused by the mutation of the lysosomal acid lipase A gene and characterized by the lysosomal accumulation of cholesteryl esters and triglycerides in many tissues. Its late onset form, cholesteryl ester storage disease, is frequently misrecognized because of a mild and nonspecific presentation that resembles more common illnesses such as metabolically associated steatotic liver disease and dyslipidemia. This review summarizes the current knowledge on cholesteryl ester storage disease and aims to increase the awareness of the disease among clinicians.