Congenital enteropathy due to enteropeptidase deficiency

Congenital enteropathy due to enteropeptidase deficiency (also known as enterokinase deficiency) is an extremely rare inherited disorder affecting the digestive system. Enteropeptidase (formerly called enterokinase) is an enzyme produced by the cells lining the duodenum (the first part of the small intestine). Its critical role is to activate trypsinogen into trypsin, which in turn activates other pancreatic digestive enzymes. When enteropeptidase is absent or deficient, the cascade of pancreatic enzyme activation is impaired, leading to severe maldigestion and malabsorption of proteins and, to a lesser extent, fats. The condition typically presents in infancy or early childhood with chronic diarrhea, failure to thrive, edema (swelling due to low protein levels in the blood — hypoproteinemia), and hypoalbuminemia. Affected infants may also exhibit vomiting, abdominal distension, and iron-deficiency anemia. The stool may be fatty or foul-smelling due to malabsorption. Laboratory findings characteristically show low levels of trypsin activity in duodenal fluid despite normal pancreatic secretion of other components. Treatment is based on oral pancreatic enzyme replacement therapy (pancreatin or pancrelipase), which bypasses the need for enteropeptidase-mediated activation by providing already-activated or exogenous pancreatic enzymes. With appropriate enzyme supplementation and nutritional support, including a protein-rich diet, affected children generally show significant clinical improvement, with resolution of diarrhea, edema, and catch-up growth. The long-term prognosis with treatment is generally favorable. The condition is caused by pathogenic variants in the TMPRSS15 gene (previously known as PRSS7), which encodes enteropeptidase.

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