An unusual case of hypercholesterolaemia with liver dysfunction

Although rare, the presentation of the genetic disease spectrum associated with lysosomal acid lipase (LAL) deficiency, a disorder named cholesteryl ester storage disease (CESD) or the more severe form of Wolman's disease, is an important condition to recognise. LAL plays an essential role in lipid catabolism and a deficiency in this enzyme results in accumulation of cholesterol esters in multiple tissues. The first clinical manifestation is often hepatomegaly, despite the multi-system nature of the disorder. Other associated features include splenomegaly, adrenal calcification, malabsorption, hypercholesterolaemia or mixed hyperlipidaemia predisposing to premature atherosclerosis, as well as liver dysfunction, which can lead to cirrhosis and liver failure. Diagnosis can be made through genetic screening, LAL activity measurement or on liver biopsy. Recent advances in treatment of LAL deficiency have been made with development of a recombinant human LAL (sebelipase alpha). Adjunctive treatment with lipid-lowering therapy continues to be standard management.