Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease

J Hepatol. 2008 Nov;49(5):810-20. doi: 10.1016/j.jhep.2008.05.016. Epub 2008 Jun 10.

Abstract

Background/aims: Citrin deficiency caused by SLC25A13 gene mutations develops into adult-onset type II citrullinemia (CTLN2) and may be accompanied with hepatic steatosis and steatohepatitis. As its clinical features remain unclear, we aimed to explore the characteristics of fatty liver disease associated with citrin deficiency.

Methods: The prevalence of hepatic steatosis in 19 CTLN2 patients was examined, and clinical features were compared with those of non-alcoholic fatty liver disease (NAFLD) patients without known SLC25A13 gene mutations.

Results: Seventeen (89%) CTLN2 patients had steatosis, and 4 (21%) had been diagnosed as having NAFLD before appearance of neuropsychological symptoms. One patient had steatohepatitis. Citrin deficiency-associated fatty livers showed a considerably lower prevalence of accompanying obesity and metabolic syndrome, higher prevalence of history of pancreatitis, and higher serum levels of pancreatic secretory trypsin inhibitor (PSTI) than fatty livers without the mutations. Receiver operating characteristic curve analyses revealed that a body mass index < 20kg/m(2) and serum PSTI>29ng/mL were associated with citrin deficiency.

Conclusions: Patients presenting with non-alcoholic fatty liver unrelated to obesity and metabolic syndrome might have citrin deficiency, and serum PSTI may be a useful indicator for distinguishing this from conventional NAFLD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carrier Proteins / blood
  • Citrullinemia / diagnosis
  • Citrullinemia / etiology*
  • Citrullinemia / genetics
  • Citrullinemia / metabolism
  • Diagnosis, Differential
  • Fatty Liver / diagnosis
  • Fatty Liver / etiology*
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Female
  • Humans
  • Male
  • Membrane Transport Proteins / deficiency*
  • Membrane Transport Proteins / genetics*
  • Metabolic Syndrome / complications
  • Middle Aged
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins / deficiency*
  • Mitochondrial Proteins / genetics*
  • Models, Biological
  • Mutation
  • Obesity / complications
  • Trypsin Inhibitor, Kazal Pancreatic
  • Young Adult

Substances

  • Carrier Proteins
  • Membrane Transport Proteins
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Proteins
  • SLC25A13 protein, human
  • SPINK1 protein, human
  • Trypsin Inhibitor, Kazal Pancreatic