Cryptogenic Cirrhosis and Sitosterolemia: A Treatable Disease If Identified but Fatal If Missed

Ann Hepatol. 2017;16(6):970-978. doi: 10.5604/01.3001.0010.5290.

Abstract

Sitosterolemia is an autosomal recessive metabolic disease caused by mutations in ABCG5 or ABCG8 genes which encode for the (ATP)-binding cassette (ABC) transporters that are responsible for the trafficking of xenosterols. Liver involvement is not a recognized manifestation of this disease, and cirrhosis has been reported only once in the medical literature. We describe a fatal case of a 21-year old South Asian male who presented with decompensated cirrhosis, and biochemical abnormalities consistent with sitosterolemia. Genetic testing showed a homozygous pathogenic mutation in ABCG5, confirming the diagnosis. Sitosterolemia is a rare, but likely under-recognized condition, and a high degree of suspicion is imperative to make the diagnosis. We propose that sitosterolemia should be included in the differential diagnosis for patients with cryptogenic cirrhosis, especially as there are effective oral therapies to treat this condition. Newly diagnosed sitosterolemia patients should undergo a thorough hepatology evaluation and follow-up to evaluate for the presence, development, and progression of any hepatic involvement.

Keywords: Cryptogenic cirrhosis. Ascites. Idiopathic cirrhosis. Sitosterolemia. Phytosterolemia. Plant sterols. Premature coronary artery disease. Macrothrombocytopenia. ABCG5. ABCG8..

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics
  • Anemia, Hemolytic / etiology
  • Anticholesteremic Agents / therapeutic use
  • Biopsy
  • Coronary Angiography
  • Coronary Artery Disease / etiology
  • DNA Mutational Analysis
  • Diet, Fat-Restricted
  • Ezetimibe / therapeutic use
  • Fatal Outcome
  • Genetic Predisposition to Disease
  • Heredity
  • Homozygote
  • Humans
  • Hypercholesterolemia / complications*
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / therapy
  • Intestinal Diseases / complications*
  • Intestinal Diseases / diagnosis
  • Intestinal Diseases / genetics
  • Intestinal Diseases / therapy
  • Lipid Metabolism, Inborn Errors / complications*
  • Lipid Metabolism, Inborn Errors / diagnosis
  • Lipid Metabolism, Inborn Errors / genetics
  • Lipid Metabolism, Inborn Errors / therapy
  • Lipoproteins / genetics
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology*
  • Male
  • Microscopy, Electron
  • Mutation
  • Pedigree
  • Phenotype
  • Phytosterols / adverse effects*
  • Phytosterols / genetics
  • Risk Factors
  • Treatment Outcome
  • Xanthomatosis / etiology
  • Young Adult

Substances

  • ABCG5 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • Anticholesteremic Agents
  • Lipoproteins
  • Phytosterols
  • Ezetimibe

Supplementary concepts

  • Sitosterolemia