P4.37: Extra-Intestinal Manifestations of Children with Genetically Confirmed Microvillus Inclusion Disease

Abstract

Objectives: Microvillous inclusion disease (MVID): congenital disorder caused by MYO5B or STX3 mutations. Pathognomonic features are severe intractable diarrhoea and malabsorption due to intestinal brush border atrophy, accumulation of lysosomal granules and microvillus inclusions in the apical cytoplasm of enterocytes. All epithelial tissues express MYO5B but gut involvement is classically described. Method: Two males: A, 2-year-old Pakistani and B, 12-month-old Kuwaiti with MYO5B mutation. Results: Patient A: Neonatal secretory diarrhea with high fluid and electrolyte requirements, deteriorated on feed introduction. Duodenal histology: blunted villi, hyperplastic crypts, loss of surface epithelium, goblet cell depletion and apoptosis. Periodic acid–Schiff (PAS) and CD10 staining suggested MVID, confirmed by electron microscopy (EM). Genetics: homozygosity of MYO5B gene: c.1087C>T mutation. He was discharged on home parenteral nutrition (PN) at 10 months with ongoing high volume and sodium demands, gradually worsening diarrhea and minor transaminitis in his first year but otherwise stable liver function. Annual PN screening showed low TMP/GFR (0.89mmol/L), elevated cystatin C (1.27mg/L), biochemical evidence of renal tubular leak and radiological signs of rickets but no nephrocalcinosis. Fanconi syndrome was diagnosed. Currently on 24hr PN (250ml/kg) with large amounts of electrolytes, phosphate, acetate with over 20 watery stools/day. He was referred for small bowel (SB) transplantation. Patient B: Neonatal watery diarrhea and severe acidosis with feed introduction. He was commenced on PN, tertiary referral to London at 2months; arriving in poor nutritional status, marked conjugated hyperbilirubinemia and transaminitis. SB mucosal biopsies demonstrated total villous atrophy, focally vacuolated superficial epithelium and few intraepithelial lymphocytes. PAS and CD10 staining suggested MVID confirmed by EM. Genetics: compound heterozygosity for MYO5B gene mutations; c.1576C>T; p. and c.2111del; p. variant. Liver biopsy: lobular cholestasis, hepatocyte giant cell transformation and bridging fibrosis. He currently tolerates small amount of an amino-acid based formula and 170ml/kg/day PN with 10-hours break; with stable diarrhea (6–7/day). Due to severe liver injury and long term PN, he is being assessed for combined liver and SB transplantation. Conclusion: MVID has variable phenotypes, with other organ involvement such as liver and kidney apart from the gut.