Category Archives: Health

While the basic defect is unknown, it has been proposed that the ultrastructural lesion that characterizes MID is best explained as an example of a normal cell component assembled in an abnormal location. The microvilli appear to be assembled on the inner surface of the intracytoplasmic vesicles rather than at the apical cell surface. Furthermore, the prominent periodic acid-Schiff staining of the apical cytoplasm (rather than the brush border), the immunofluores-cent staining of specific brush border enzymes in the apical cytoplasm and the accumulation of secretory granules in the apical region of some cells all suggest that an abnormality of exocytosis exists. Brush border proteins normally reach the plasma membrane at the base of the apical microvilli. They are synthesized in the rough endoplasmic reticulum, processed and assembled as membrane proteins in the Golgi apparatus, and transported to the cell surface along a chain of connecting intracytoplasmic vesicles. However, against this theory, normal exocytosis and localization of two brush border-targeted enzymes (sucrase-isomaltase and dipeptidylpeptidase intravenous) have been demonstrated in biopsies and organ cultures from MID patients. These studies suggested that both direct and indirect constitutive pathways of exocytosis were intact in MID. It was hypothesized that there may be an as yet uncharacterized regulated pathway of exocytosis in enterocytes that is abnormal in MID. (more…)

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. (more…)

A barium study showed no evidence of a congenital short bowel or an obstruction. Hirschsprung’s disease was excluded when a full thickness rectal biopsy showed normal ganglion cells. Urinary catecholamines were assessed to rule out a neuroendocrine tumour and were reported to be in the normal range. Assessments revealed no immunological abnormality. At four months of age, when the patient weighed 3.0 kg, endoscopic duodenal biopsies were obtained. With examination by light microscopy, sections of small intestinal mucosa exhibited partial to total villous atrophy, a hypocel-lular lamina propria and crypt hypoplasia. The poorly defined brush border in the surface epithelium and the periodic acid-Schiff positivity of the apical cytoplasm of the entero-cytes suggested MID. Suction biopsies of the rectal mucosa were unremarkable. Because of the increased risk of perforation associated with suction jejunal biopsies in malnourished infants, repeat jejunal biopsy with a Carey capsule and primary fixation of tissue for electron microscopy were delayed until the child was six months of age and weighed 5.5 kg. Electron microscopic evaluation of this second proximal small intestinal biopsy revealed intracytoplasmic microvillous inclusion bodies, confirming the diagnosis of MID (Figure 1). (more…)

A nine-day-old white male presented with a history of watery diarrhea that had developed gradually in the first few days after birth. He was born to nonconsanguineous parents at 36 weeks’ gestation. The pregnancy was uncomplicated, with no evidence of polyhydramnios. There was meconium-stained liquor at delivery, but the immediate postnatal period was uneventful. Birth weight was 2.74 kg. The patient was discharged on day 3 weighing 2.43 kg. At home, he was breastfed every 2 to 3 h and continued to have three stools per day, of which at least one was described as watery. On day 9, he was brought to the hospital because he was lethargic and feeding poorly. In the emergency room, he was noted to be poorly responsive and was estimated to be 10% dehydrated, weighing only 1.8 kg. The physical examination was otherwise unremarkable. He was hypernatremic and acidotic, with a capillary blood pH of 6.97 but only a modest anion gap of 22 mmol/L (normal 5 to 15 mmol/L). Oral feeding was stopped, and fluids were replaced intravenously. Bicarbonate was infused to partially correct the acidosis. Broad spectrum antibiotic therapy was initiated after cultures were taken. Of the many possible causes of watery diarrhea (Table 1), a viral or allergic enteropathy was initially considered to be most likely. However, stool cultures and rapid screens for rotavirus and adenovirus were subsequently negative. Blood, urine and cerebrospinal fluid were sterile. (more…)