Rare hereditary cause of chronic pancreatitis in a young male: SPINK1 mutation

Abstract

Hereditary chronic pancreatitis associated with a mutation in the serine protease inhibitor, Kazal Type-1 (SPINK-1 gene) is extremely rare. The SPINK1 mutation results in trypsinogen activation which predisposes to chronic pancreatitis predominately when combined with CFTR gene mutations. It presents as either chronic or recurrent acute pancreatitis. Symptom control and management of complications is important. Active surveillance with cross-sectional imaging for pancreatic malignancy in individuals with hereditary pancreatitis is advocated due to individuals being high risk. We present an unusual case of a young male who initially presented with renal colic and was incidentally diagnosed with severe chronic pancreatitis on abdominal imaging, with genetic testing confirming a homozygous SPINK1 mutation.

Monogenic Causes in the Type 1 Diabetes Genetics Consortium Cohort: Low Genetic Risk for Autoimmunity in Case Selection

“…In the 29 families without affected parent, we also observed other dominant pathogenic variants, 1 in each of INS (frameshift predicted to evade nonsense-mediated decay; see Supplementary Figure 1 in ( 14 )), KCNJ11 (OMIM 616329), p.227Glu > Lys, de novo, found in both neonatal and acquired diabetes ( 15 , 16 ), GCK p.258Gly > Ser, Pathogenic, and KLF11 (OMIM 610508 VUS). Finally, 1 sibling pair shared a splicing variant in SPINK1 (OMIM 167800), reported in hereditary pancreatitis ( 17 ) a condition often resulting in diabetes and whose primary manifestations may be mild enough to be missed ( 18 , 19 ).…”

Multidisciplinary treatment of chronic active Epstein-Barr virus infection with multiple complications: a case report

“…Hereditary pancreatitis is linked to mutations in PRSS1, CFTR, SPINK1, CTSB, CASR, PSP/Reg, etc. (6)(7)(8)(9). But no genes associated with hereditary pancreatitis were found.…”

Imaging of Pancreatitis in Children

“…40,55,56 The main pathophysiology of genetic mutation is that the pancreas is auto-digested by various mechanisms such as disturbing the normal trypsin pathway, lacking in dilution and alkalinization of the pancreatic secretions or inducing endoplasmic reticulum stress. 39,57,58 Up to 80.0% of hereditary pancreatitis cases show PRSS1 mutation, while SPINK1 mutation is likely a disease modifier when concomitant with other genetic mutations and environmental factors. 39,58,59 Imaging of genetic mutation-related pancreatitis depends on the stage of disease (Figure 5A-D).…”

“…39,57,58 Up to 80.0% of hereditary pancreatitis cases show PRSS1 mutation, while SPINK1 mutation is likely a disease modifier when concomitant with other genetic mutations and environmental factors. 39,58,59 Imaging of genetic mutation-related pancreatitis depends on the stage of disease (Figure 5A-D). MRCP and genetic tests are recommended in every pediatric patient with ARP or lack of an obvious etiology of pancreatitis.…”