Congenital hepatic fibrosis in 3 siblings with phosphomannose isomerase deficiency

Research output: Contribution to journalArticle


Congenital hepatic fibrosis is a rare disorder of intrahepatic bile ducts with the persistence of embryological bile duct structures in ductal plate configuration. Three siblings aged 18, 17 and 14 years old were found to have congenital hepatic fibrosis associated with a deficiency of the enzyme phosphomannose isomerase. The clinical symptoms were recurrent attacks of persistent vomiting with diarrhea and mild hepatomegaly. The biochemical abnormalities included elevated serum transferases during attacks, clotting factor deficiencies and persistent hypoalbuminemia. In the youngest patient protein-losing enteropathy was present. Liver biopsies of the three patients taken when they were 1, 3 and 14 years old showed an excess of bile duct structures in ductal plate configuration with mild fibrosis in the portal triads. In one patient the liver biopsy was repeated after 18 years and showed only a mild progression of fibrosis in the portal triads. Duodenal biopsies taken in infancy in two of the three patients did not show any abnormalities. Recognition of phosphomannose isomerase deficiency in association with congenital hepatic fibrosis and protein-losing enteropathy is important, because some of the clinical symptoms are potentially treatable by oral mannose therapy.


  • T. J. De Koning
  • P. G.J. Nikkels
  • L. Dorland
  • J. Bekhof
  • J. E.A.R. De Schrijver
  • J. Van Hattum
  • O. P. Van Diggelen
  • M. Duran
  • R. Berger
  • B. T. Poll-The
External organisations
  • Wilhelmina Children’s Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical and Health Sciences


  • CDG syndrome, Congenital hepatic fibrosis, Phosphomannose isomerase deficiency
Original languageEnglish
Pages (from-to)101-105
Number of pages5
JournalVirchows Archiv
Issue number1
Publication statusPublished - 2000 Jan 1
Publication categoryResearch
Externally publishedYes