Isolated deficient alpha 6 beta 4 integrin expression in the gut associated with intractable diarrhea

Background: An infant born with pyloric atresia had development of intracta ble diarrhea and was found to have total epithelial detachment of gastric a nd small and large bowel mucosa. She had no skin abnormalities. Parental co nsanguinity and pyloric atresia in a sibling who died without autopsy sugge st an inherited origin for this disorder. The purpose of this study was to examine defects in intestinal and skin cell adhesion. Methods: Histologic, immunohistochemical, and ultrastructural characteristi cs of the skin and gut of the patient were compared with that of normal con trol subjects. Distribution of adhesion molecules was determined. Results: Immunofluorescent analysis of the digestive mucosa showed alpha 6 beta 4 integrin expression deficiency at the epithelial cell-lamina propria junction. Ultrastructural examination of the digestive mucosa revealed a c omplete epithelial detachment with a cleavage plane lying between the lamin a densa and the basal pole of the enterocytes. Consistent with the absence of skin blistering, integrin alpha 6 beta 4 was expressed at the dermal-epi dermal junction. Electron micrographs of skin biopsy specimens showed the p resence of normal hemidesmosomes and the absence of dermal-epidermal dysadh esion. Conclusion: It was postulated that this patient had protracted diarrhea rel ated to epithelial detachment of the digestive mucosa as a consequence of a deficiency of an integrin alpha 6 beta 4 isoform specific to the gut.