Tufting Enteropathy

Tufting enteropathy (intestinal epithelial dysplasia) is a congenital enteropathy presenting with severe intractable watery diarrhoea in the first weeks of life, caused by variants in EPCAM or, less often, SPINT2. Histology shows distinctive focal epithelial tufts, villous atrophy and crypt hyperplasia.

The incidence is about 1 in 50 000 to 100 000 live births in Western Europe, higher in populations with consanguinity, such as the Arabian Gulf. Inheritance is autosomal recessive.

EPCAM disease is often isolated or associated with punctate keratitis. SPINT2 disease is syndromic, with choanal atresia, hypertelorism and corneal erosions, and carries a link to congenital sodium diarrhoea. Most children depend on parenteral nutrition, though a minority (especially with milder EPCAM variants) achieve enteral autonomy.

Pathophysiology.

Defective epithelial cell adhesion and basement membrane interaction (from EPCAM loss of function) disturbs the organisation of enterocytes, causing tufts, villous atrophy and impaired absorption. Secretory diarrhoea results.

• Profuse watery diarrhoea beginning in the first weeks (often within 2 weeks), persisting during fasting, with dehydration and failure to thrive.
• Metabolic acidosis, electrolyte disorders and poor growth.
• Extraintestinal features: punctate keratitis, choanal atresia, dysmorphism and skin or hair anomalies.
• Complications: catheter sepsis, thrombosis, cholestasis and metabolic bone disease.

Red flags.

• Neonatal dehydration and acidosis with secretory diarrhoea.
• Corneal disease or choanal atresia in a child with diarrhoea.
• Fever with central line, liver dysfunction or bleeding.

• Small bowel (and colon) biopsy: villous atrophy, crypt hyperplasia, and epithelial tufts of crowded, teardrop shaped enterocytes on the surface. Tufts may be sparse in early biopsies, and the biopsy may need repeating.
• Genetic testing of EPCAM (including deletion analysis) and SPINT2.
• Stool electrolytes to confirm secretory diarrhoea, and exclusion of infection, allergy, microvillus inclusion disease and immunodeficiency.
• Ophthalmic examination, nasal assessment and liver tests.

Differential diagnosis. Microvillus inclusion disease, congenital sodium diarrhoea, congenital chloride diarrhoea, autoimmune enteropathy, coeliac disease, infection, protein allergy, and other genetic diarrhoeal disorders.

• Rehydration and electrolyte replacement tailored to stool losses and blood gas.
• Parenteral nutrition through a tunnelled central venous catheter, with energy 80 to 100 kcal/kg/day, amino acids 2.5 to 3 g/kg/day and lipid emulsion up to 1 g/kg/day, with fish-oil-based emulsions to reduce liver disease. Enteral feeds are introduced gradually using an amino-acid-based or extensively hydrolysed formula, as tolerated.
• Line protection: aseptic technique, lock therapy and early treatment of infection. Monitor for intestinal failure associated liver disease, bone disease and growth.
• Immunosuppression (steroids) and other drugs have not shown consistent benefit.
• Intestinal transplantation (with or without liver) for parenteral nutrition failure, or complications such as recurrent sepsis, thrombosis of central veins or liver failure.
• Treat keratitis with ophthalmology, and manage choanal atresia surgically.
• Genetic counselling.

Monitoring. Growth, electrolytes, liver function, central venous access, micronutrients, bone health and eyes.

Referral and escalation. Refer to a paediatric intestinal failure and transplant centre early.