INTRACTABLE DIARRHEA OF INFANCY WITH EPITHELIAL AND BASEMENT-MEMBRANEABNORMALITIES

We describe a form of intractable diarrhea in six children (four girls ) with similar clinical histories and identical histopathologic featur es. The children had watery diarrhea of neonatal onset requiring total parenteral nutrition, Two had siblings who had died of diarrhea in th e first year of life; two others are sisters, Repeated duodenal or jej unal biopsies revealed villous atrophy with normal or hyperplastic and regenerative cryptae, normal cellularity of the lamina mesenteril pro pria, and no signs of T-cell activation. The main histologic features are epithelial dysplasia with focal crowding and disorganization of th e surface enterocytes, pseudocystic formation of the glands, and abnor mal regenerative cryptae. The basement membrane components were studie d with polyclonal antibodies on frozen specimens,, and were compared w ith biopsy specimens from patients with celiac disease or autoimmune e nteropathy. Relative to the control subjects, there was faint and irre gular deposition of laminin at the epithelium-lamina mesenterii propri a interface, whereas deposits of heparan sulfate proteoglycan were lar ge and lamellar, The primary or secondary nature of these modification s of the basement membrane remains to be determined, but the modificat ions might be related to epithelial abnormalities and to the severity of this neonatal diarrhea, which resisted all treatment and necessitat ed permanent total parenteral nutrition.