Phosphomannose isomerase deficiency as a cause of congenital hepatic fibrosis and protein-losing enteropathy

Abstract

ITHIN JUST a few months, three different groups W have reported a potentially treatable inborn error of glycoprotein metabolism presenting with congenital hepatic fibrosis and protein-losing enteropathy (l-3). The disorder causes defective protein glycosylation due to a deficiency of the enzyme phosphomannose isomerase (PMI). Inborn errors of metabolism are not usually associated with a developmental disorder of the liver and protein loss in the gut. This defect might lead to new insights in fetal development of intrahepatic bile ducts and disorders like ductal plate malformation. Niehues et al. (1) reported a young male patient with a severe protein-losing enteropathy, recurrent thrombosis and vomiting. Antithrombin III activity was reduced. Simultaneously, De Koning et al. (2) described three adolescent siblings of a consanguineous family with congenital hepatic fibrosis and recurrent episodes of vomiting accompanied by diarrhea. A few months later, Jaeken et al. (3) reported two additional patients with diarrhea, protein-losing enteropathy and decreased activities of antithrombin III, piotein C and protein S. Liver biopsy also showed congenital hepatic fibrosis. In all the patients the same enzyme defect, viz a deficiency of PMI, was found. However, the authors of these papers were not the first to recognize this peculiar combination of symptoms. The clinical phenotype of protein-losing enteropathy, congenital hepatic fibrosis and antithrombin III deficiency was first described by Pedersen & Tygstrup (4) in 1980. In their original paper two siblings were reported with recurrent thrombosis, gastro-intestinal protein loss and con-