De novo PRSS1 p.Asn29Ile mutation causing hereditary pancreatitis in an Indian child

Hereditary pancreatitis is a rare genetic disorder, usually associated with gain-of-function mutations in the PRSS1 gene. While in the Indian pediatric population, the SPINK1 mutations are more frequently reported, making PRSS1 mutations, particularly the de novo variants, rare. An 11-year-old school-going Indian girl presented with recurrent acute pancreatitis beginning at the age of 5 years. This progressed to chronic pancreatitis by the age of 10 years. Metabolic, autoimmune, structural, and infectious causes were excluded. The genetic test done revealed a heterozygous pathogenic PRSS1 c.86A>T (p.Asn29Ile) variant. In the absence of family history, this was consistent with a likely de novo mutation. No pathogenic variants were detected in SPINK1, CFTR, CTRC, or CPA1. Pancreatic enzyme replacement therapy and dietary modification reduced the frequency of attacks and preserved her growth. This case highlights the importance of genetic evaluation in children who present with unexplained recurrent pancreatitis, even when there is no positive family history. Early identification of PRSS1 mutation allows for appropriate counseling, long-term surveillance, and complication prevention.