Genetic features and variants of hereditary pancreatitis in children

Abstract

Chronic pancreatitis is a polyetiological disease characterized by progressive structural changes of the pancreas with the development of its exo- and endocrine insufficiency. In childhood, possible causes of chronic pancreatitis may be obstruction of the ducts of pancreas due to gallstone disease, chronic cholecystitis with biliary sludge, anomalies of the excretory ducts; obesity and hyperlipidemia; injuries of the abdomen and infectious lesions of the gland. In recent years, due to better diagnostics, new probable variants of chronic pancreatitis have been found: autoimmune and hereditary. According to reviewing data, more than 70% of children with idiopathic chronic pancreatitis have genetic mutations of SFTR, PRSS1 and SPINK1 genes, both single and combined. This leads to disturbance of the balance of activation and inactivation of trypsinogen in the pancreatic tissue. Severe mutations can be an independent cause of chronic pancreatitis, mild mutations manifest after environmental impact. The study included: a) family cases of pancreatitis (16 families, 37 patients); b) patients with idiopathic pancreatitis, i. e., with the presence of acute recurrent or chronic pancreatitis of unknown etiology and the absence of similar diseases among relatives (n = 21). An analysis of 19 frequent mutations in 5 known genes (PRSS1, SPINK1, CTRC, CFTR, CPA1) associated with the development of NP was carried out. Results: mutations were detected in 11 of 58 patients (19%), and in two of 190 healthy donors (2%); p <0.0001. The cause of the development of pancreatitis was identified in members of 5 of 16 (31%) families, and only in 1 of 27 (4%) patients with an idiopathic form of the disease.