Genetic Abnormalities in Pancreatitis: An Update on Diagnosis, Clinical Features, and Treatment

Abstract

Several pancreatitis susceptibility genes have been identified to date. A relationship between a mutation in the cationic trypsinogen (protease serine 1, PRSS1) gene and hereditary pancreatitis (HP) was first identified in 1996. Currently, HP has been defined as either two or more individuals within a family exhibiting pancreatitis for two or more generations, or pancreatitis linked to mutation of the PRSS1 gene. In 2000, a mutation in the serine protease inhibitor gene (Kazal type 1: SPINK1) was reported to be related to sporadic pancreatitis of unknown etiology. This paper reviews and summarizes the current published data on the pancreatitis susceptibility genes, mainly PRSS1 and SPINK1 genes, and introduces a diagnostic and therapeutic approach for dealing with patients with these gene mutations. Patients with these genetic predispositions, both children and adults, have often been initially diagnosed with idiopathic acute pancreatitis, in approximately 20–50% of pediatric cases and 28–80% of adult cases. In such patients, where the etiology is unknown, genetic testing, which requires pre-test and post-test genetic counselling, may prove helpful. Patients with chronic pancreatitis (CP) due to SPINK1 gene mutation and HP patients have a potentially high risk of pancreatic exocrine insufficiency, diabetes mellitus, and, of particular importance, pancreatic cancer. Thus, these patients require careful long-term follow-up and management. Specifically, symptomatic CP patients often need endoscopic therapy or surgery, often following a step-up approach beginning with endoscopic therapy and progressing to surgery if necessary, which is similar to the therapeutic approach for patients with CP due to other etiologies. It is important that clinicians are aware of the characteristics of patients with pancreatitis susceptibility genetic abnormalities.

Genetic Risk Factors in Early-Onset Nonalcoholic Chronic Pancreatitis: An Update

“…Genetic counseling both before and after molecular testing is strongly recommended in all patients. Importantly, CP patients having genetic variants should be carefully followed by the clinicians since they may have a high risk of developing further medical complications such as pancreatic exocrine insufficiency, diabetes mellitus and pancreatic cancer [85].…”

Genetic determinants of pancreatitis: relevance in severe hypertriglyceridemia

“…Acute pancreatitis is hallmarked by inflammation of the pancreas, resulting in severe epigastric pain, along with elevated serum pancreatic enzymesparticularly pancreatic lipase -sometimes together with radiographic findings [2 ]. Acute pancreatitis has an annual incidence of 10 to 35 per 100 000 individuals in North America, and compared to other acute conditions it is associated with relatively longer duration of hospitalization and higher mortality [3].…”

“…Acute pancreatitis episodes may recur leading to long term complications such as chronic pancreatitis, pancreatic pseudocyst formation, pancreatic necrosis, and pancreatic failure with endocrine and exocrine insufficiency [2 & ]. The pathophysiology of acute pancreatitis has been attributed to diverse mechanisms including pathological calcium signaling, mitochondrial dysfunction, endoplasmic reticulum stress, an impaired unfolded protein response and impaired autophagy [2 ]. However, the most well accepted core mechanism is autodigestion due to premature trypsinogen activation into trypsin, which is the main enzyme responsible for the activation of digestive enzymes following its secretion into the duodenum.…”

Canine Pancreatitis: The Development of the Pancreatic Inflammatory Condition and the Clinical-Therapeutic Approach

“…Research on the study of pancreatitis in humans has been gaining enormous importance. This fact can be explained due to new investigations of a genetic character that show the occurrence of changes in the enzyme trypsin (7,12). According to Watson (7) the "pathophysiology of this disease is believed to be similar in dogs and cats".…”

“…A small portion of the trypsin precursors undergo their own activation process inside the zymogen granules. However, autolysis does not occur due to inactivation mediated by other substances such as molecules auxiliary to segregation, in addition to inhibitors responsible for trypsin secretion -PSTI, also known as inhibitors of Kazal serine protease type-1 (SPINK 1) (7,12).…”