The SPINK1 c.101A>G variant in a 6-year-old with recurrent pancreatitis: causal mutation or phenotypic modifier?

Abstract

The serine peptidase inhibitor Kazal-type 1 (SPINK1) p.Asn34Ser variant is a pancreatitis risk factor often linked to a c.-4141G>T upstream enhancer mutation that reduces protective enzyme expression. Symptoms usually begin in late adolescence or early adulthood and typically require environmental triggers. Early pediatric presentation is exceptionally rare. A six-year-old male presented with recurrent periumbilical and epigastric abdominal pain. Investigations revealed elevated serum amylase and lipase levels and a mildly enlarged pancreas. Fecal elastase-1 testing indicated severe exocrine pancreatic insufficiency. There was a positive paternal history of early-adulthood pancreatitis. Confirmatory whole-exome sequencing identified a heterozygous c.101A>G (p.Asn34Ser) SPINK1 mutation. Initial management included bowel rest, analgesics, and intravenous hydration, followed by pancreatic enzyme replacement therapy. Parents were counseled to strictly avoid environmental triggers, such as high-fat meals. At the six-month follow-up, the patient remained asymptomatic and pain-free, with successful weight gain. Identifying SPINK1 variants in early-childhood recurrent pancreatitis is critical. Understanding its pathogenic mechanism, potentially driven by linked upstream regulatory mutations, guides targeted interventions. Early enzyme replacement and strict trigger avoidance are essential to prevent future attacks and to optimize pediatric growth.