Homozygous SPINK1-Related Pancreatitis Complicated by Exocrine Pancreatic Insufficiency: A Case Report

Background: Genetically mediated pancreatitis is a major cause of recurrent acute pancreatitis and chronic pancreatitis in children. While autosomal dominant hereditary pancreatitis is classically linked to PRSS1 mutations, variants in SPINK1 are increasingly recognized as important disease modifiers, particularly when present in a homozygous state. These variants may lead to early disease onset and rapid progression toward chronic pancreatitis and exocrine pancreatic insufficiency. Case Presentation: We report the case of a 16-year-old girl with recurrent acute pancreatitis beginning in childhood, occurring three to four times per year, without identifiable secondary causes or a family history. Imaging revealed dilation of the main pancreatic duct and features suggestive of chronic pancreatitis. Endoscopic ultrasound demonstrated parenchymal atrophy, intraductal lithiasis, and mucous plugging, consistent with lithiasic chronic pancreatitis. Genetic testing identified homozygous SPINK1 variants (c.101A>G [p.Asn34Ser] and c.56-37T>C), along with a homozygous intronic CFTR variant, supporting a diagnosis of genetically mediated pancreatitis Conclusion: This case illustrates the aggressive clinical course of homozygous SPINK1-associated pancreatitis in pediatric patients, characterized by early progression to chronic pancreatitis and severe exocrine pancreatic insufficiency. It highlights the critical role of early genetic testing, detailed endosonographic evaluation, and comprehensive functional assessment in children with recurrent pancreatitis. Early diagnosis and individualized multidisciplinary management are essential to optimize nutritional status, preserve pancreatic function, and improve long-term outcomes.