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Mechanism of Disease In cells missing the vital LAL enzyme, upregulation of cholesterol synthesis resulting from cellular dysfunction leads to ongoing lysosomal accumulation 1 LAL-D is characterized by Disrupted Cholesterol Metabolism and Intracellular Accumulation of Lipids Across Organ Systems 1,3 LAL-D LEADS TO PROGRESSIVE MULTISYSTEM ORGAN DAMAGE 2 LAL-D is characterized by disrupted cholesterol metabolism and intracellular accumulation of lipids across organ systems 2 Lipa Mutation 1 Missing or decreased LAL enzyme 1 Lysosomal accumulation of CE/TG 1 Dysregulated lipid metabolism 1 Liver 1,2 Hepatomegaly Hepatic injury ALT AST POSSIBLE/POTENTIAL CONSEQUENCes Microvesicular or mixed steatosis Fibrosis Cirrhosis Portal hypertension Liver failure HEART 1,2 Dyslipidemia LDL-C HDL-C POSSIBLE/POTENTIAL CONSEQUENCes Accelerated atherosclerosis Coronary artery disease Stroke Myocardial infarction Spleen 1,2,4 Splenomegaly POSSIBLE/POTENTIAL CONSEQUENCes Anemia Thrombocytopenia Risk of traumatic rupture and/or splenectomy Intestine 1,2 Intestinal lipid accumulation POSSIBLE/POTENTIAL CONSEQUENCes Abdominal pain Malabsorption Growth failure Abbreviations: ALT, alanine aminotransferase

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Acetyl coenzyme A: a central metabolite and second messenger