congenital enteropathy due to enteropeptidase deficiency

Congenital enteropathy due to enteropeptidase deficiency is a rare genetic disorder that primarily affects the digestive system. It is characterized by early-onset failure to thrive, edema, hypoproteinemia, persistent diarrhea, and fat malabsorption, all occurring in the context of very low or absent trypsin activity in the duodenal fluid. The condition is caused by pathogenic variants in the TMPRSS15 gene, which plays a crucial role in initiating the activation of digestive enzymes. Precise prevalence estimates are not well established, but the condition is considered rare.

Infants with this condition typically present with significant gastrointestinal challenges, including poor growth, feeding difficulties, and swelling due to low protein levels. They also experience persistent diarrhea and steatorrhea resulting from fat malabsorption, which is linked to a marked reduction in trypsin activity. Not all individuals experience every symptom, and the severity can vary considerably, underscoring the variability in clinical presentation.

The condition results from pathogenic variants in the TMPRSS15 gene, which encodes the enzyme enteropeptidase. Enteropeptidase is essential for converting trypsinogen to trypsin, a key step in protein digestion. Congenital enteropathy due to enteropeptidase deficiency follows an autosomal recessive inheritance pattern, meaning that an affected individual inherits two altered copies of the gene, one from each parent. Consequently, carrier parents have a 25% chance of having an affected child with each pregnancy.

Currently, management focuses on supportive care and symptom management rather than a specific disease-targeted therapy. Treatment is individualized and typically involves a multidisciplinary team to address nutritional deficiencies, manage dehydration, and support overall growth and development. Genetic counseling is recommended to help families understand the inheritance pattern and discuss family planning options. Patients should discuss all management strategies with their healthcare team to determine the most appropriate supportive interventions.

The outlook for congenital enteropathy due to enteropeptidase deficiency varies widely between individuals, with outcomes depending on symptom severity, age at diagnosis, and the quality of supportive care provided. While the early presentation of the condition can be challenging, timely nutritional support and comprehensive management may improve growth and overall health. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors and support groups for additional guidance.