Microvillus atrophy is the leading cause of secretory diarrhea in the first weeks of life. A group of infants with a familial enteropathy characterized by protracted diarrhea from birth and villus hypoplastic atrophy had been described in 1978 by Davidson et al. The term microvillus atrophy was first used to identify the disease in 1982. The typical clinical presentation is watery profuse secretory diarrhea starting in the first hours of life. The peak age of onset is the early neonatal period. Although later-onset cases have been described, cases have never been described beyond the first 2-3 months of life.

The three variants of the disease have been identified: congenital microvillus atrophy, late-onset microvillus atrophy, and atypical microvillus atrophy.

In congenital microvillus atrophy, diarrhea starts in the first few days of life and is immediately life threatening. Oral alimentation in nutritionally significant amounts is impossible. In late-onset microvillus atrophy, diarrhea starts later in life, usually in the second month. Diarrhea tends to be less severe than in the other form, and some alimentation is possible. A few cases have been termed atypical microvillus atrophy, in which the onset can be congenital or late, but the histologic picture is different.

The hallmark of the disease is the electron microscopic finding of disrupted enterocytic microvilli (i.e, digitations of the apical membrane of the intestinal epithelial cell protruding into the lumen) and the appearance of characteristic inclusion vacuoles, the inner surfaces of which are lined by typical microvilli. Both lesions are seen only on electron microscopy. In a notable percentage of consanguineous families, more than one child is affected; therefore, the disease appears to be transmitted as an autosomal recessive trait.

The pathogenesis of the disease remains unknown. Severe perturbations of the microvillar cytoskeleton may disrupt the transport of brush border components that have been assembled at the apical membrane. Biopsy samples from the small intestine of 2 infants with congenital microvillus atrophy were examined to analyze the membrane protein of the brush border. The samples demonstrated striking diminutions of the myosin bands. The genetic defect appears likely to cause abnormal binding of the myosin to the actin cable. In one patient with late-onset microvillus atrophy, the molecular defect involved a protein, supposedly identified as vinculin.

Other studies have suggested an alternative hypothesis, namely that a defect in the autophagocytosis pathway or an increase in enterocyte apoptosis and proliferation explains the abnormalities observed in congenital microvillus diesease.

Reference:

http://emedicine.medscape.com/article/928100-overview