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Introduction: Microvillous Inclusion Disease (MVID) (OMIM#251850) is a rare autosomal recessive condition caused by mutations or deletions mostly in the MYH6 gene but also STX3 and STXBP2 genes. It is characterized by protracted diarrhea with severe congenital alteration of the intestinal epithelium resulting in watery diarrhea, metabolic acidosis, failure to thrive, and permanent malabsorption that normally leads to a lifelong dependency on total parenteral nutrition (TPN) and the eventual possibility of bowel transplantation . Histological hallmarks of MVID in small intestinal biopsies are hypoplastic, atrophic, or disorganized villi without crypt hypertrophy, or immune cell infiltrate and, at the intestinal cellular level, microvillus atrophy, intracellular accumulation of brush border enzymes, and microvillus inclusions in the cytoplasm. It is caused by a dysfunction of myosin Vb protein encoded by the MYO5B gene; at least 41 different mutations have been discovered . It is thought that these mutations can cause intracellular trafficking defects causing impairment of the apical enterocytes recycling and reduced expression of the apical proteins at the brush border membrane; also, this defect can cause fusion of transport vesicles of brush border proteins in the cytoplasm causing the Microvillous inclusions . Objective: Present a case of MVID with confirmed clinical features and histology with a novel mutation in MYH6 and RYR2 genes. Case report: We report two siblings, the oldest sibling is four years old, and the youngest is two years old; both are TPN-dependent and diagnosed as neonates with MVID both of whom presented with severe congenital diarrhea. Histopathology revealed epithelial cells with poorly formed brush borders and many cells with intracytoplasmic inclusions. Electron microscopy showed microvilli-containing inclusions within the apical cytoplasm in the enterocytes. Genetic results revealed that both siblings have maternally inherited heterozygous deletion of 2.62 kb in exons 32-33 of the MYO5B gene. Conclusions: There are very few MVID cases reported in the literature. To date, 188 patients are registered in the International Microvillous Inclusion Disease Patient Registry . None of those patients were reported to have a heterozygous deletion involving exons 32-33 of the MYO5B gene.
Gastroenterology | Pediatrics
Alatorre-Jimenez, Moises; Weller, Brandi; Orlick, Meike; and San Pablo, William, "Two Siblings With Microvillous Inclusion Disease" (2022). Posters. 295.