CFTR variant-associated hereditary pancreatitis complicated by diabetes mellitus: a case report and literature review

Hereditary pancreatitis (HP) is a rare autosomal dominant disorder characterized by recurrent episodes of pancreatic inflammation leading to chronic pancreatic damage. We report a 38-year-old Chinese male with a heterozygous cystic fibrosis transmembrane conductance regulator ( CFTR ) intronic variant (c.1210-11T>G) who presented with pancreatic diabetes (type 3c diabetes) and an otherwise “silent” pancreatic phenotype. He had a family history of similar manifestations (father and brother with pancreatogenic diabetes). Genetic testing identified the CFTR c.1210-11T>G variant, which is known to affect splicing (TG12-5T allele). The variant meets ACMG criteria for pathogenicity. Segregation analysis confirmed all affected relatives carried this variant. No other significant genetic findings (e.g. SPINK1 , PRSS1 ) were detected. The patient’s presentation was dominated by diabetes with minimal abdominal symptoms; however, pancreatic imaging revealed changes consistent with chronic pancreatitis (pancreatic atrophy and ductal irregularity). The diagnosis of hereditary chronic pancreatitis was established based on clinical, imaging and genetic criteria. In the Discussion, we compare this case to reported CFTR -related pancreatitis cases and highlight the importance of considering CFTR variants in familial idiopathic pancreatitis with diabetes. This case underscores that CFTR single heterozygous variants (especially bicarbonate-defective alleles) can cause a pancreatitis-predominant phenotype. It also emphasizes the need for comprehensive genetic testing in atypical diabetes.