Would You Figure It Out? Differential Diagnoses: Beyond the Usual

Abstract

The Synageva BioPharma-sponsored symposium discussed the differential diagnoses for liver diseases that may be under-recognised in clinical settings, with a focus on lysosomal acid lipase deficiency (LAL D). LAL D is a lysosomal storage disorder caused by deficient activity of the lysosomal acid lipase enzyme, resulting in the accumulation of cholesteryl esters and triglycerides throughout the body, predominantly in the liver, spleen, gastrointestinal tract, and blood vessel walls. LAL D is a progressive, multisystem disease with early mortality and significant morbidity that is characterised by hepatic dysfunction and dyslipidaemia. Evidence suggests that LAL D may be substantially underdiagnosed or misdiagnosed, which is critical given that disease progression can be unpredictable, with liver failure and/or accelerated atherosclerosis potentially contributing to early mortality. However, a definitive diagnosis of LAL D can be made using a LAL enzyme-based biochemical test, thereby allowing for active monitoring of patients to reduce the potential for disease complications. To raise awareness of LAL D, this symposium, chaired by Prof Vlad Ratziu, centered on the presentation of patient cases by Dr Lauren Johansen, Prof Christophe Moreno, and Prof Ali Canbay, who discussed the path to diagnosing LAL D in children and adults. In addition, Dr Mark Bechter of Synageva BioPharma provided an overview of current data from an ongoing Phase III clinical trial assessing the efficacy and safety of sebelipase alfa, a recombinant LAL replacement therapy, in children and adults with LAL D.