Very early-onset gastrointestinal and immune dysregulation due to TPP2 deficiency: A case report from south India

Background: Tripeptidyl peptidase II (TPPII) deficiency is a rare autosomal recessive primary immunodeficiency caused by mutations in the TPP2 gene. It is characterized by immune dysregulation, recurrent infections, autoimmunity, developmental delay, and very early-onset gastrointestinal manifestations that may mimic inflammatory bowel disease (IBD). Early diagnosis is essential to guide management and consider curative treatment options such as hematopoietic stem cell transplantation (HSCT).

Methods: We describe a single case from a tertiary pediatric center in South India. Clinical evaluation, endoscopic assessment, immunophenotyping, and whole exome sequencing (WES) were performed to investigate severe neonatal-onset gastrointestinal disease with systemic immune involvement.

Results: A female neonate born to third-degree consanguineous parents presented in the neonatal period with profuse diarrhea, progressing to intestinal perforation, recurrent sepsis, failure to thrive, and developmental delay. Endoscopic evaluation revealed colitis with ulceration and chronic inflammation. Immunologic assessment showed reduced naïve CD4? and CD8? T cells and decreased memory B cells. Whole exome sequencing identified a homozygous TPP2 variant (c.3392C>T; p.Ser1131Phe), with both parents confirmed as heterozygous carriers. The patient was managed with nutritional rehabilitation, corticosteroids, sirolimus, and prophylactic antimicrobials. HSCT was discussed as a definitive therapeutic option.

Conclusion: TPPII deficiency is a rare but important cause of very early-onset gastrointestinal disease with systemic immune dysregulation. This case highlights the need to suspect monogenic immune disorders in neonates presenting with severe, atypical enteropathy and multisystem involvement. Early immunologic evaluation and genetic confirmation are critical to guide targeted therapy and timely consideration of HSCT for improved outcomes.

Dr. Mounika Bazar, from India, has completed advanced training in Pediatric Gastroenterology, Hepatology, and Nutrition and is actively engaged in clinical practice and academic work. She has presented her research at national and international conferences and contributes to academic writing and clinical research. Her work reflects a commitment to academic excellence, with an evolving focus on healthcare systems, quality improvement, and medical education.