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

Tripeptidyl peptidase II (TPPII) deficiency is an extremely rare autosomal recessive primary immunodeficiency caused by biallelic mutations in the TPP2 gene. It manifests with a combination of immune dysregulation, recurrent infections, autoimmune cytopenias, and developmental delay. Gastrointestinal features resembling very early-onset inflammatory bowel disease (VEO-IBD) may dominate the early clinical picture, complicating diagnosis.

We report a female infant born to third-degree consanguineous parents who presented in the neonatal period with profuse diarrhea following ingestion of Acorus calamus (a traditional herbal root). Her illness progressed rapidly with intestinal perforation, septic shock, and prolonged hospitalization. Surgical exploration revealed multiple perforations in the ileum and colon. Despite parenteral nutrition and elemental feeding, she had persistent diarrhea, poor weight gain, and signs of inflammatory colitis.

Immunologic evaluation showed low naïve CD4+ and CD8+ T cells, decreased memory B cells, and absence of class-switched B cells. Whole exome sequencing identified a homozygous missense mutation in TPP2 (c.3392C>T; p.Ser1131Phe), with both parents confirmed as heterozygous carriers. These findings confirmed the diagnosis of TPPII deficiency. She required long-term nutritional support, immunosuppressants (steroids and sirolimus), and broad-spectrum antimicrobial prophylaxis. Hematopoietic stem cell transplantation (HSCT) was considered as a potential curative option.

This case adds to the limited global reports of TPPII deficiency and highlights a unique presentation dominated by neonatal gastrointestinal involvement and immune dysfunction. It emphasizes the importance of early genetic testing and immunologic profiling in infants with unexplained colitis and multisystem disease. Timely diagnosis can facilitate appropriate management and consideration of curative therapies such as HSCT.

To be updated shortly..