Genetic intractable diarrhea of infancy

Genetic intractable diarrhea of infancy (also known as congenital intractable diarrhea) is a group of rare inherited disorders characterized by severe, persistent, watery diarrhea that begins in the first weeks to months of life and does not respond to standard medical management. These conditions primarily affect the gastrointestinal system, specifically the intestinal epithelium, leading to profound malabsorption of nutrients and fluids. The diarrhea is typically so severe that affected infants develop life-threatening dehydration, electrolyte imbalances, metabolic acidosis, and failure to thrive. Without aggressive intervention, the condition can be fatal in early infancy. This Orphanet grouping (ORPHA:363300) encompasses multiple genetic etiologies that converge on the clinical phenotype of intractable infantile diarrhea. Underlying causes may include defects in enterocyte structure and function (such as microvillus inclusion disease caused by MYO5B mutations, or tufting enteropathy caused by EPCAM or SPINT2 mutations), congenital chloride or sodium diarrhea, and other rare monogenic disorders affecting intestinal epithelial transport or development. Diagnosis typically requires a combination of clinical evaluation, intestinal biopsy with electron microscopy, and genetic testing to identify the specific molecular defect. Treatment is largely supportive and often requires long-term total parenteral nutrition (TPN) to maintain adequate hydration and nutritional status. Some patients may eventually tolerate partial enteral feeding depending on the underlying genetic cause. Intestinal transplantation may be considered in cases refractory to medical management or when complications of long-term TPN, such as liver disease, develop. Prognosis varies significantly depending on the specific genetic etiology, with some forms carrying a more favorable outlook than others. Early genetic diagnosis is important for guiding management, family counseling, and identifying patients who may benefit from emerging targeted therapies.

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