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The initial report of an apparently familial enteropathy, characterized by protracted diarrhea from birth and hypoplastic villous atrophy, was in 1978 by Davidson et al. Electron microscopy of surface enterocytes from a jejunal biopsy specimen of one of their patients revealed intracytoplasmic inclusions composed of neatly arranged brush border microvilli. Similar inclusions have since been reported in other children presenting with protracted watery diarrhea starting soon after birth. The term ‘MID’ was proposed to designate the condition because it highlights the characteristic ultrastructural lesion and clearly differentiates the condition from other entities. The condition appears to be inherited as an autosomal recessive disorder. While consanguinity was not present in our case, Candy et al found that 20% of infants with this disease were the products of consanguineous relationships, and three of the nine infants reported by Cutz et al had a sibling affected. A high frequency of MID in the Navajo Indian population of Arizona has been observed. While uncommon, MID is the most common cause of severe refractory diarrhea in the neonatal period in North America. Distinctive intracytoplasmic inclusions are found in the absorptive cells of the small intestine and have been described in colonocytes in MID. However, as in this case, colonocytes may be normal. This suggests that there may be variability in the severity of this disorder or perhaps even different molecular defects resulting in a similar phenotype. MID is also characterized pathologically by a severe, generalized, hypoplastic enteropathy of the small intestine. A variable degree of villous atrophy is also seen in intestinal epithelial dysplasia or ‘tufting’ disease, another cause of intractable diarrhea in infancy. The characteristic finding in intestinal epithelial dysplasia is disorganization of the surface enterocytes with focal tufting. Unlike these two causes of neonatal diarrhea, the ultrastructure of the enterocyte is normal in congenital chloride diarrhea, diarrhea secondary to defective sodium-hydrogen exchange, primary malabsorption of bile acids and congenital short bowel. Watery diarrhea in the neonate may also be due to carbohydrate malabsorption, which results in primarily osmotic diarrhea. In our patient, the diagnosis of secretory diarrhea was supported by the persistence of profuse watery diarrhea when not being fed, the absence of a stool osmolar gap when fed monosaccharide-containing formulas, and elevated sodium and chloride concentrations in the stool. The history was not typical of congenital chloride diarrhea or diarrhea secondary to a deficiency of sodium-hydrogen exchange. These disorders are both characterized by a maternal history of polyhydramnios (consistent with intrauterine diarrhea) and abdominal distension of the neonate at birth. Our patient and other patients reported to have MID do not have these features, although the reason for the postnatal onset of diarrhea is not known. In addition, patients with congenital chloride diarrhea develop metabolic alkalosis, while our patient was typical of patients previously reported to have MID, in that he manifested acidosis due to bicarbonate loss in the stools. The functional consequence of hypoplastic enteropathy is an inability to absorb ingested nutrients and profuse watery diarrhea resulting from a net secretory state in the intestine. In vivo and in vitro studies of small intestinal electrolyte transport in these infants suggest that while mucosal surface area is much impaired, mucosal enterocytes retain the capacity for limited but active sodium-dependent mucosal to serosal glucose transport. Also, the watery diarrhea results from a combination of reduced mucosal to serosal ion fluxes, and elevated basal secretion of both chloride and sodium ions. While it has never been investigated, the possibility of a dysregulated, sodium-coupled, bicarbonate secretory process may explain the elevated basal sodium secretion and the massive luminal losses of bicarbonate that were observed in this infant and that are typical ofMID. Another possible explanation, at a molecular level, for the massive secretory diarrhea seen in these patients (despite apparent crypt hypoplasia) was posed by Michail et al. That study showed that the mRNA expression of three apical transporters involved in sodium absorption - sodium hydrogen exchangers (NHE-2 and NHE-3), and the sodium glucose transporter (SGLT1) - were markedly reduced. These data suggest that the morphological changes of MID are associated with secondary decreases in mRNA coding for apically located ion transport proteins. If you are concerned about high cost of meds these days but still want to make sure your problem is treated properly, it's a good idea to visit the Canadian Health&Care Mall for efficient medications of best quality, which will also be delivered to you any time any place.