Summary

Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea sometimes causing irreversible intestinal failure. At present, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000-100,000 live births in Western Europe. The prevalence appears to be higher in areas with a high degree of consanguinity and in patients of Arabic origin. Infants develop a watery diarrhea within the first days after birth and the diarrhea persists in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal, rectal or esophageal atresia. IED is thought to be related to abnormal enterocyte development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients. Histology shows various degrees of villous atrophy, with minimal or absent mononuclear cell infiltration of the lamina propria, but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes and focal crowding, resembling tufts. Several associated specific features were reported including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG) in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of alpha2beta1 integrin adhesion molecules. A transgenic mice model in which the gene encoding the transcription factor Elf3 was disrupted presented morphologic features resembling IED. Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s) have not been yet identified making prenatal diagnosis unavailable. Some infants have a milder phenotype than others but in most patients the severity of the intestinal malabsorption (even with enteral feeding) makes them totally dependent on daily long-term parenteral nutrition with a subsequent risk of complications. IED develops into an indication for intestinal transplantation. The timing of referral for this indication is crucial before the onset of severe complications.

Expert reviewer(s)

• Pr Nicole BROUSSE
• Pr Olivier GOULET
• Dr Natacha PATEY-MARIAUD DE SERRES
• Dr Frank M. RUEMMELE
• Dr Julie SALOMON