Hepatic and Extrahepatic Sources and Manifestations in Endoplasmic Reticulum Storage Diseases

Int J Mol Sci. 2021 May 28;22(11):5778. doi: 10.3390/ijms22115778.

Abstract

Alpha-1-antitrypsin (AAT) and fibrinogen are secretory acute phase reactant proteins. Circulating AAT and fibrinogen are synthesized exclusively in the liver. Mutations in the encoding genes result in conformational abnormalities of the two molecules that aggregate within the rough endoplasmic reticulum (RER) instead of being regularly exported. That results in AAT-deficiency (AATD) and in hereditary hypofibrinogenemia with hepatic storage (HHHS). The association of plasma deficiency and liver storage identifies a new group of pathologies: endoplasmic reticulum storage disease (ERSD).

Keywords: alpha-1-antitrypsin; deficiency; extrahepatic; fibrinogen; hepatic; manifestation.

Publication types

  • Review

MeSH terms

  • Afibrinogenemia / genetics
  • Afibrinogenemia / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Hepatocytes / cytology
  • Hepatocytes / metabolism
  • Hepatocytes / ultrastructure
  • Humans
  • Kupffer Cells / metabolism
  • Kupffer Cells / ultrastructure
  • Liver / cytology
  • Liver / metabolism*
  • Microscopy, Electron, Transmission
  • Mutation
  • alpha 1-Antitrypsin / genetics
  • alpha 1-Antitrypsin / metabolism
  • alpha 1-Antitrypsin Deficiency / genetics
  • alpha 1-Antitrypsin Deficiency / metabolism*

Substances

  • alpha 1-Antitrypsin