Microvillus Inclusion Disease

Microvillus inclusion disease is a congenital disorder of enterocyte polarity and apical trafficking, caused most often by biallelic variants in MYO5B. It presents as intractable, profuse secretory diarrhoea in the first days of life (early onset), or from 2 to 3 months of age (late onset), with dependence on parenteral nutrition.

It is rare, with an estimated incidence below 1 in 100 000, and is more frequent in populations with consanguinity, including Navajo and Middle Eastern communities. Variants in STX3 and STXBP2 cause similar disease.

Stool volume is large (up to 150 to 300 mL/kg/day), persists during fasting, and causes dehydration, acidosis and failure to thrive. Some MYO5B variants also cause cholestasis.

Pathophysiology.

Failure of apical trafficking leads to loss of brush border microvilli and formation of intracellular microvillus inclusions in enterocytes. Villous atrophy, impaired sodium and nutrient absorption, and increased chloride secretion result.

• Early onset: severe watery diarrhoea within the first 72 hours of life, polyhydramnios, dehydration, metabolic acidosis and weight loss.
• Late onset: diarrhoea from 2 to 3 months of age, usually less severe.
• Failure to thrive, with PN dependence, and complications including catheter related sepsis and thrombosis, and cholestatic liver disease.

Red flags.

• Severe dehydration and shock with acidosis in a neonate.
• Catheter infection, jaundice, liver dysfunction or bleeding.
• Persistent diarrhoea during fasting.

• Persistent profuse diarrhoea that continues when feeds are stopped, with high stool sodium and acidosis.
• Small bowel biopsy: villous atrophy with normal crypts, absent brush border on periodic acid-Schiff stain and CD10 staining (cytoplasmic rather than apical), and microvillus inclusions on electron microscopy.
• Genetic testing (MYO5B, STX3, STXBP2) is confirmatory and increasingly replaces electron microscopy.
• Exclude infection, sodium diarrhoea, chloride diarrhoea, tufting enteropathy and allergy.

Differential diagnosis. Tufting enteropathy, congenital sodium diarrhoea, congenital chloride diarrhoea, autoimmune enteropathy, cow's milk protein allergy, infectious diarrhoea, glucose galactose malabsorption and immunodeficiency.

• Fluid and electrolyte replacement: IV fluids replacing stool losses volume for volume with sodium, potassium and bicarbonate.
• Parenteral nutrition with a central line (energy 80 to 100 kcal/kg/day, amino acids 2.5 to 3 g/kg/day, fish-oil-based or mixed lipid emulsion 1 g/kg/day), with trace elements and vitamins. Trophic enteral feeds are given in some cases.
• Line care: strict aseptic technique, ethanol locks or taurolidine locks, and early treatment of line sepsis. Monitor liver function for intestinal failure associated liver disease.
• Antisecretory drugs (octreotide, somatostatin analogues) have limited effect.
• Intestinal transplantation (isolated or combined with the liver) is considered for failing parenteral nutrition, repeated line complications or liver failure. Late onset disease may partly improve with age.
• Genetic counselling for the family.

Monitoring. Growth, electrolytes, liver function, central line complications, micronutrients and bone health.

Referral and escalation. Refer to a national intestinal failure and transplant unit early.