Hepatosteatosis from Lysosomal Acid Lipase Deficiency
KeywordsLAL deficiency Lysosomal acid lipase NAFLD Steatosis Herniotomy Laparoscopy
History and Clinical Course
Due to the suggestive histological picture with exclusively microvesicular steatosis, a test for activity of lysosomal acid lipase (LAL) was performed at the visit at the hepatology outpatient clinic and LAL activity was reported to be 0.0 nmol/3 h (normal 0.1–2.0 nmol/3 h) which is diagnostic of LAL deficiency (LAL-D). A homozygous mutation of E8SJM (c.894G>A) was confirmed. LAL-D is a rare and under-diagnosed autosomal-recessive lysosomal storage disease. Complete lack of LAL activity, traditionally known as Wolman disease, is lethal within the first year of life due to liver failure and malabsorption. Minimal residual LAL activity is referred to as cholesterol ester storage disease (CESD) and typically manifests in childhood or early adulthood with microvesicular hepatic steatosis progressing to fibrosis, cirrhosis, and potentially hepatocellular carcinoma.1 Orange coloration of steatosis is a result of predominant cholesterol deposition and different from the yellow appearance ensuing from triglyceride accumulation associated with more common fatty liver diagnoses such as nonalcoholic or alcoholic fatty liver disease. Hallmark laboratory abnormalities include high LDL, total cholesterol, and triglycerides which are mainly attributed to activation of de novo lipogenesis via SREBP1c as a result of low cytoplasmatic concentration of free cholesterol and fatty acids.2 Low HDL is a consequence of decreased activity of LXR-dependent HDL production.2 Children or adults with LAL-D usually progress to end-stage liver disease with its complications early in life and are at high risk of developing premature atherosclerosis with cerebral or myocardial infarction. It is crucial to raise awareness of this rare disease as specific enzyme replacement therapy with sebelipase alfa has become available and timely diagnosis may therefore be life-saving for affected subjects.3
SZ—drafting and critical revision of the manuscript for important intellectual content; FP—surgical care of patient; EA—establishing diagnosis, drafting, and finalizing of manuscript.
Open access funding provided by Paracelsus Medical University.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
- 3.Burton BK, Balwani M, Feillet F, Barić I, Burrow TA, Camarena Grande C, Coker M, Consuelo-Sánchez A, Deegan P, Di Rocco M, Enns GM, Erbe R, Ezgu F, Ficicioglu C, Furuya KN, Kane J, Laukaitis C, Mengel E, Neilan EG, Nightingale S, Peters H, Scarpa M, Schwab KO, Smolka V, Valayannopoulos V, Wood M, Goodman Z, Yang Y, Eckert S, Rojas-Caro S, Quinn AG. A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency. The New England Journal of Medicine 2015;373:1010–20.CrossRefGoogle Scholar
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