Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Pancreatitis, chronic [K86.9]

OMIM numbers: 167800, 276000 (PRSS1), 167790 (SPINK1), 602421 (CFTR), 601405 (CTRC), 114850 (CPA1)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh

Scientific Background

Pancreatitis is generally divided into two forms – acute and chronic. Chronic pancreatitis is a complex, highly variable and chronic inflammatory syndrome, characterized by initially repetitive episodes of pancreatitis which may later develop into chronic inflammation of the pancreas. A progressive fibrosis of the pancreatic parenchyma, parenchymal calcification and pancreatic duct concrements eventually lead to irreversible destruction of the organ due to loss of exocrine and endocrine functioning. The risk of developing a ductal adenocarcinoma of the pancreas increases significantly.

Signs and symptoms include repetitive, severe abdominal pain with increased serum pancreatic enzymes, typical pancreatic pain, steatorrhea and diabetes mellitus. The incidence of chronic pancreatitis is estimated to be 3.5-10 in 100,000 within industrialized countries; the main cause is thought to be chronic alcohol abuse. Other risk factors are genetic changes, hypertriglyceridemia, autoimmunity and hypercalcemia, among others. In an attempt to categorize the disease into various clinical entities, in the literature terms such as hereditary, idiopathic, familial and sporadic pancreatitis are used. So far, there is no standard, universal definition; especially the term “hereditary pancreatitis” is used in different contexts.

According to the current state of knowledge, changes in the genes PRSS1 (cationic trypsinogen), SPINK1 (serine protease inhibitor Kazal type I), CFTR (cystic fibrosis transmembrane conductance regulator) and CTRC (chymotrypsin C) are thought to be predisposing and involved in the origin and penetrance of chronic pancreatitis to different degrees. Various inheritance patterns are seen, including what is known as digenic inheritance (transheterozygosity), i.e. mutations are present in two of the above-mentioned genes simultaneously. In approx. 49% of all patients suffering from chronic pancreatitis mutations in the above-mentioned genes can be detected. Stepwise diagnostics is done according to the frequency of described mutations.