SPINK-1 Polymorphism as a Pancreatitis Risk Factor

Abstract

Genetic etiologies are responsible for 10% of pancreatitis cases. Serine protease inhibitor Kazal-type 1 (SPINK-1) polymorphisms are seen in approximately 2% of the US population and are attributed to 5-6% of all chronic pancreatitis cases and 15-40% of idiopathic pancreatitis cases. On average, irrespective of gender, those with SPINK-1 polymorphisms who develop pancreatitis do so at a younger age (mid 20's) when compared to those without (mid 30's). A 56 y.o. male with a past medical history of recurrent chronic pancreatitis with heterogeneous SPINK-1 mutation (diagnosed at age 27) presented with severe left lower quadrant (LLQ) abdominal pain. The patient had 7 pancreatitis flares within the past year. He had a remote alcohol and smoking history though he denied recent use. On admission, the patient's vitals were within normal limits and physical exam was significant only for LLQ tenderness and hypoactive bowel sounds. Labs revealed AST 14 U/L, ALT 12 U/L, Alk Phos 63 U/L, lipase 43 U/L, total cholesterol 138 mg/dL, triglycerides 129 mg/dL, and INR 1.4. CT abdomen/pelvis w/ contrast revealed an enlarging known pseudocyst in the pancreatic tail measuring 3.4 x 5.3 cm as well as peripancreatic inflammatory changes surrounding the distal body and extending along the spleen. [Figure 1.] Patient saw resolution of symptoms post supportive management and IV hydration. The SPINK-1 gene encodes a trypsin inhibitor, which in those with a gene polymorphism, fails to adequately prevent trypsinogen from autoactivating and damaging the pancreas. [Figure 2] SPINK-1 mutations predispose patients to acute pancreatitis, earlier onset chronic pancreatitis, and pancreatic cancer. Mutations do not follow autosomal dominant or recessive patterns and heterozygotes and homozygotes display similar rates of disease process making the mutation a disease modifier rather than a direct cause. Treatment for hereditary pancreatitis is the same as that of other causes of pancreatitis. Rarely, in severe cases of chronic pancreatitis, pancreatectomy with islet cell transplantation is considered. Though regular genetic testing is not used for SPINK-1, early identification of those with polymorphisms may help lead to lifestyle modifications to reduce overall risk of disease development. Our patient's unfortunate history of pancreatitis is likely secondary to previous insults from alcohol and smoking in the setting of heterozygous SPINK-1 mutation.2899_A Figure 1. 5.2x2.7 cystic lesion was noted on initial CT abdomen with contrast. (Left) Subsequent CT abdomen with contrast two months later (on current admission) showed the lesion had increased to 5.3x 3.4cm. (Right)2899_B Figure 2. Pathogenesis of SPINK-1 polymorphism in the development of Pancreatitis.