Elevation of gamma-glutamyl transferase in adult: Should we think about progressive familiar intrahepatic cholestasis?

Dig Liver Dis. 2016 Feb;48(2):203-5. doi: 10.1016/j.dld.2015.11.002. Epub 2015 Dec 1.

Abstract

Background: There are three types of progressive familial intrahepatic cholestasis (PFIC). Type 3 is characterized by elevated gamma-glutamyl transferase (γ-GT) and it can be diagnosed in adolescence/adulthood. The genetic defect of PFIC 3 appears to explain the pathogenesis of intrahepatic cholestasis of pregnancy (ICP).

Aims: Draw attention to this rare disease, especially in adulthood, and clarify the association between ICP and PFIC 3.

Results: We describe a series of cases from a Portuguese northern family with two brothers presenting chronic cholestasis since adolescence. Brother 1: since 15-years-old with pruritus and elevated γ-GT ∼6x. Brother 2: pre-term, due to severe maternal pruritus and jaundice, since 13-years-old with pruritus, jaundice and ∼8x γ-GT elevation. Common causes of cholestasis were excluded and liver histologies were nonspecific. Research for mutation on ABCB4 gene showed mutations in both alleles.

Conclusion: Disease and mechanisms that determine cholestasis are complex and their understanding may provide new therapeutics.

Keywords: Cholestasis; Gamma-glutamyl transferase; MDR3; Progressive familial intrahepatic cholestasis.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / deficiency*
  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adolescent
  • Cholestasis, Intrahepatic / complications
  • Cholestasis, Intrahepatic / enzymology*
  • Cholestasis, Intrahepatic / genetics*
  • Female
  • Humans
  • Jaundice, Obstructive / etiology
  • Male
  • Mothers
  • Mutation
  • Pedigree
  • Portugal
  • Pregnancy
  • Pregnancy Complications / genetics*
  • Pruritus / etiology
  • Siblings*
  • gamma-Glutamyltransferase / blood*

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • multidrug resistance protein 3
  • gamma-Glutamyltransferase
  • gamma-glutamyltransferase, human

Supplementary concepts

  • Cholestasis, progressive familial intrahepatic 3
  • Intrahepatic Cholestasis of Pregnancy