Figures & data
Figure 1 The clinical spectrum of LAL-deficiency. The clinical spectrum of LAL-deficiency ranges from severe variants with early death, previously referred to as Wolman disease, to milder variants manifesting during childhood or adulthood, known as CESD.
Abbreviations: CESD, cholesteryl ester storage disease; LAL, lysosomal acid lipase; CE, cholesteryl esters; TG, triglycerides.
Figure 2 Summary of the mechanisms of disease. Cholesterol is physiologically taken up as cholesteryl esters via the LDL receptor – endocytosis pathway into lysosomes and then hydrolyzed by LAL enzyme (A). In cases of defective LAL activity cholesteryl esters and triglycerides accumulate in lysosomes, leading to universal microvesicular hepatic steatosis with development of fibrosis (C). Cholesterol accumulation causes orange coloration of the fatty liver (B), which is different from the triglyceride accumulation characteristic of common-type non-alcoholic fatty liver disease. (A) Published with permission of Alexion Pharmaceuticals. (B) and (C) Reproduced from Zandanell S, Primavesi F, Aigner E. Hepatosteatosis from Lysosomal Acid Lipase Deficiency. J Gastrointest Surg. 2019;23(3):601-602 (http://creativecommons.org/licenses/by/4.0/).Citation44
Abbreviations: LAL, lysosomal acid lipase; CE, cholesteryl ester; TG, triglyceride; LAL, lysosomal acid lipase; LDL, low-density lipoprotein.
Figure 3 Development of the clinical manifestations in LAL-D. Although the mechanisms are universal as depicted in the sequence of events on the left, clinical manifestations and consequences range from liver disease to atherosclerosis and malabsorption.
Abbreviations: LAL, lysosomal acid lipase; CE, cholesteryl esters; TG, triglycerides; ALT, aspartate transaminase; AST, alanine aminotransferase; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol; ESLD, end-stage liver disease; MCI, myocardial infarction.
Figure 4 Hepatosplenomegaly. In LAL-D, the relative degree of hepatomegaly is usually prevalent over the relative degree of splenomegaly. The exclusion of hematological disorders should prompt the work-up for inherited storage disorders.
Abbreviation: LAL-D, lysosomal acid lipase deficiency.
Figure 5 Vacuolated lymphocyte. Vacuolated lymphocytes may provide a diagnostic clue in many but not all lysosomal storage disorders. Although not massive in LAL-D, the presence of vacuolated lymphocytes can provide important diagnostic hints toward an underlying lysosomal storage disorder.
Abbreviation: LAL-D, lysosomal acid lipase deficiency.
