In the first group, histologic analysis differentiates diseases characterized by mononuclear infiltration of the lamina propria with activated T-cells, such as various forms of autoimmune diarrhea. On the other hand, a rather heterogeneous group of primary intestinal epithelial changes without mononuclear infiltration includes severe diarrheal diseases such as microvillous atrophy/microvillous inclusion disease (MVA/MVID) and tufting enteropathy.

MVA/MVID is best diagnosed electronmicroscopally by demonstrating typical autophagic vacuoles containing microvilli. Tufting enteropathy or intestinal epithelial dysplasia presents under the light microscope with focal crowding of disorganized enterocytes extruding from the tips of the villi.

Intractable, often total parenteral nutrition dependent diarrheal diseases caused by congenital molecular intestinal transport defects Include congenital chloride diarrhea (CCD) and congenital sodium diarrhea (CSD). CCD is associated with over 30 mutations detected in the SLC26L3 gene which encodes a chloride/bicarbonate exchanger and is clinically characterized by massive losses of chloride and fluid via the feces leading to hypochloremia and metabolic alkalosis. CSD is caused by defect in sodium absorption due to a block in the exchange proton versus sodium leading to hyponatremia and metabolic acidosis. We have recently found a gene and so far five specific mutations associated with patients suffering from CSD in three different countries. We are currently performing studies of RNA expression to characterize the function of this gene and the functional consequences caused by the mutations found so far.