Pancreatitis associated with SPINK1 mutation and pancreaticobiliary maljunction

Chronic Pancreatitis in Children

“…SPINK1, together with the protease inhibitor α1-antitrypsin, bind to activated trypsin and inhibit its activity 15 . Current research has identified various genes which have been recognized as being related to hereditary and idiopathic CP, such as PRSS1, CFTR and SPINK1 10,16,19,23,25 26 that there were various deregulated genes in the gallbladders of PBM children. The Bcl2 modifying factor (BMF) protein has a single Bcl2 homology domain, and belongs to the BH3-only proteins, which work as apoptotic activators 26 .…”

“…Factor group 16 Examples Toxic/metabolic: 11.0-16.0% 11,16,21 medications (ie, azathioprine sodium, 6-mercaptopurine, mesalamine 17 ), passive smoking exposure, hypertriglyceridemia, chronic kidney disease, alcohol use, active smoking, propionic acidemia 11 Genetic: 15.0% 21 , 67.0% 11 , 73.0% 16 CFTR 14.0-28.0% 11,22 , SPINK1 23 19.0-20.0% 11,22 , PRSS1 33.0-43.0% 11,22 , CTRC 3.0-7.0% 11,22 Autoimmune/Immunologic factors Autoimmune pancreatitis (AIP); 4.0-14.0% 11,16,21,22 Inflammatory bowel disease 17 Miscellaneous Acute recurrent pancreatitis, post-necrotic severe acute pancreatitis, vascular disease/ischemia, post-irradiation Obstruction: 33.0-45.0% 11,21,22 Pancreas divisum 16.0-35.0% 11,16,21 , annular pancreas, choledochal cysts or biliary cyst, pancreaticobiliary malunion 23 3.0-19.0% 11,16,24 , gallstones 4.0% 11,16 , sphincter of Oddi dysfunction, duct occlusion (e.g., tumor), duodenal diverticulum 17 , posttraumatic pancreatic duct scars CFTR=cystic fibrosis trans membrane conductance regulator gene; SPINK-1=serine protease inhibitor kazal type 1; PRSS1=protease, serine 1; CTRC=trypsinogen-degrading enzyme chymotrypsin C (Chymotrypsin C gene); CP=chronic pancreatitis protein levels in gallstone patients, and significantly higher in both the cytoplasm and nucleus of the PBM children than in the controls.…”

“…A PBM can lead to pancreatitis by biliopancreatic reflux 32 . The inborn PBM identification is proven by visualization of the biliary and pancreatic ductal systems on the ERCP 23,33 . One study reported that 72.0% of PBM cases could be detected on the MRCP 34 .…”

“…Most cases of CP have a history of acute pancreatitis. Symptoms raising suspicion for CP include presenting with abdominal pain 23 , 74.0-100.0% 9,11,16 , recurrent acute pancreatitis, 83.0% 11 , steatorrhea, 10.0% 11 , and diabetes, 1.0-9.0% 9,11 . The median age at the first attack of acute pancreatitis and diagnosis of CP are 6.8 (IQ 4.5, 12.1) and 9.9 (IQ 6.1, 14.0) years 11 , respectively.…”

“…MRCP is a noninvasive diagnostic method without contrast application that shows multiplanar visualization of the biliary and pancreatic ducts 34,37 . Standard MRCP is helpful and noninvasive in providing diagnostic figures similar to ERCP in a great proportion of pediatric CP 23 (Figure 1), and thus MRCP should be the primary imaging tool used, particularly if the chance of therapeutic…”