Cholesteryl ester storage disease: Review of the findings in 135 reported patients with an underdiagnosed disease

  • Bernstein D
  • Hülkova H
  • Bialer M
 et al. 
  • 122

    Readers

    Mendeley users who have this article in their library.
  • 118

    Citations

    Citations of this article.

Abstract

Cholesteryl ester storage disease (CESD) is caused by deficient lysosomal acid lipase (LAL) activity, predominantly resulting in cholesteryl ester (CE) accumulation, particularly in the liver, spleen, and macrophages throughout the body. The disease is characterized by microvesicular steatosis leading to liver failure, accelerated atherosclerosis and premature demise. Although CESD is rare, it is likely that many patients are unrecognized or misdiagnosed. Here, the findings in 135 CESD patients described in the literature are reviewed. Diagnoses were based on liver biopsies, LAL deficiency and/or LAL gene (LIPA) mutations. Hepatomegaly was present in 99.3% of patients; 74% also had splenomegaly. When reported, most patients had elevated serum total cholesterol, LDL-cholesterol, triglycerides, and transaminases (AST, ALT, or both), while HDL-cholesterol was decreased. All 112 liver biopsied patients had the characteristic pathology, which is progressive, and includes microvesicular steatosis, which leads to fibrosis, micronodular cirrhosis, and ultimately to liver failure. Pathognomonic birefringent CE crystals or their remnant clefts were observed in hepatic cells. Extrahepatic manifestations included portal hypertension, esophageal varices, and accelerated atherosclerosis. Liver failure in 17 reported patients resulted in liver transplantation and/or death. Genotyping identified 31 LIPA mutations in 55 patients; 61% of mutations were the common exon 8 splice-junction mutation (E8SJM-1G>A), for which 18 patients were homozygous. Genotype/phenotype correlations were limited; however, E8SJM-1G>A homozygotes typically had early-onset, slowly progressive disease. Supportive treatment included cholestyramine, statins, and, ultimately, liver transplantation. Recombinant LAL replacement was shown to be effective in animal models, and recently, a phase I/II clinical trial demonstrated its safety and indicated its potential metabolic efficacy. © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Author-supplied keywords

  • Cholesteryl ester storage disease
  • Elevated serum transaminases
  • Hepatomegaly
  • Lysosomal acid lipase deficiency
  • Lysosomal storage disease
  • Micronodular cirrhosis
  • Microvesicular steatosis
  • Non-alcoholic fatty liver disease (NAFLD)
  • Non-alcoholic steatohepatitis
  • Type 2b dyslipidemia

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Donna L. Bernstein

  • Helena Hülkova

  • Martin G. Bialer

  • Robert J. Desnick

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free