Distinguishing Lysosomal Acid Lipase Deficiency From Familial Hypercholesterolemia

Figures

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  Figure 1. Intracellular Biochemical Features of LAL Deficiency Hepatic low-density lipoprotein cholesterol (LDL-C) metabolism in (left) an individual who is healthy and (right) a patient with a deficiency in lysosomal acid lipase (LAL). In the patient with lysosomal acid lipase deficiency, there is impaired catabolism of low-density lipoprotein particles within the lysosome, thus resulting in reduced hydrolysis of cholesterol esters (CE) and triglycerides (TG). Secondary to low intracellular levels of free cholesterol (FC) and fatty acids (FA), 3 biosynthetic pathways are activated: cholesterol biosynthesis (elevated [↑] 3-hydroxy-3-methyl-glutaryl-coenzyme A [HMG-CoA] reductase), cholesterol ester formation (elevated [↑] acyl-coenzyme A: cholesterol acyltransferase [ACAT]), and fatty acid biosynthesis. This increase in lipid and esterified sterol mass is associated with increased very low-density lipoprotein cholesterol (VLDL) production and secretion. FFA = free fatty acid; LDL-R = low density lipoprotein receptor; SREBP = sterol regulatory element binding protein.

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  Figure 2. LAL-D Diagnostic Algorithm Lysosomal acid lipase deficiency (LAL-D) can occur in patients with a body mass index BMI >30 kg/m2. ALT = alanine transaminase; AST = aspartate transaminase; FCH = familial combined hyperlipidemia; HDL-C = high density lipoprotein cholesterol; HeFH = hereditary familial hypercholesterolemia; LAL = lysosomal acid lipase; LDL = low-density lipoprotein.