Enteral feed was tolerated, however, the PN therapy still contributing to most of the required calories. Later, a gastrostomy tube was inserted and elemental milk formula was given. The infant required PN therapy through a central line. The enterocytes of the duodenum show denudation and loss of the microvilli on their luminal surface with uneven gapping and spacing as well.Īfter exclusion of MYO5B gene mutation, WES was performed, detecting a homozygous nonsense gene mutation in STX3 (g59562908 c>T NM_0041774:c.739C>T (p.(Arg247*). b Transmission electron microscopy (×25,000) shows microvillus inclusions and large membrane-bound microvillus inclusions in the apical cytoplasm of the enterocyte. Histology of duodenal biopsy specimens: a Hematoxylin and eosin stain (H&E, ×40), near total villous atrophy with no significant intraepithelial lymphocytosis, inflammation, or crypt hyperplasia. Histology of the small intestinal biopsy showed subtotal villous atrophy (Fig 1a), and the EM study was consistent with MVID (Fig. Abdominal ultrasound study was unremarkable. Extensive workup excluded infectious, metabolic, mitochondrial, immune deficiency, endocrine, and renal disorders.
#GAPPED ACIDOSIS FULL#
The infant required admission to the pediatric intensive care unit (PICU) because of hypotension, hypoglycemia, and metabolic acidosis.Ī full septic workup was done, and empirical intravenous antibiotic therapy was given. Family history was remarkable for early neonatal death due to undiagnosed metabolic acidosis in a sibling and cousins. Upon admission, he was found to be dehydrated, with stunted growth, and unremarkable systemic examination apart from mild abdominal distension. The infant was transferred to our institute for further workup because of severe vomiting, mild diarrhea, loss of weight, and metabolic acidosis, which had started at the age of 3 days. Birth weight was appropriate for gestational age. Case ReportĪ 19-day-old male Saudi infant was born at term by normal vaginal delivery to a non-consanguineous couple, following an uneventful pregnancy.
This report suggests that WES is a robust method for diagnosing difficult cases of congenital gastrointestinal disorders. To the best of our knowledge, this is the third reported case in the literature. We are reporting the case of an infant with a MVID variant, caused by STX3 homozygous gene mutation detected by WES.
Enterocytes in the classic and MVID variant display characteristic microvillus inclusions, which might arise from the fusion of apical transport or recycling vesicles under conditions of reduced delivery to the apical plasma membrane. Interestingly, tolerance towards enteral feeds was noted, however, still requiring partial parenteral nutrition (PN) and sodium bicarbonate supplements. These 2 children presented with watery diarrhea and severe metabolic acidosis. STX3 is an apical receptor involved in membrane fusion of apical vesicles in enterocytes. This new mutation was detected by WES, and it leads to loss of function of STX3. described 2 children with a MVID variant caused by a new homozygous mutation in the syntaxin 3 (STX3) gene. These mutations result in mislocalization of apical proteins and disrupted enterocyte polarization. In 2008, mutations in MYO5B were identified as causal for MVID. Immune staining techniques for small intestinal biopsy, directed against CD10, a neutral membrane-associated peptidase, can further help in the diagnosis of MVID. The accumulation of periodic acid-Schiff-positive granules within the apical cytoplasm of the immature enterocytes in the upper crypts is highly characteristic of MVID. Gastrointestinal endoscopy is usually normal, however, standard intestinal histology shows a variable degree of villous atrophy without marked crypt hyperplasia. All children with MVID require TPN, and they are at risk of developing cholestasis and liver failure secondary to TPN. Physical examination shows massive abdominal distension with fluid-filled bowel loops. Ĭhildren with the typical MVID will rapidly develop metabolic acidosis and signs of hypotonic dehydration because of profuse diarrheal losses. However, milder variants of MVID that present later have been reported. The typical MVID is a severe and intractable enteropathy requiring total parenteral nutrition (TPN) for the delivery of fluids and calories, and it is inevitably fatal without continuous intravenous nutrition or intestinal transplantation.
Microvillus inclusion disease (MVID) is a rare autosomal recessive disease that presents with severe and intractable secretory diarrhea in neonates and infants.
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