Combined SPINK1 mutations induce early-onset severe chronic pancreatitis in a child with severe obesity

SUMMARY: The most frequent causes of pancreatitis classically have been known to be gallstones or alcohol. However, genetics can also play a key role in predisposing patients to both chronic and acute pancreatitis. The serine protease inhibitor Kazal type 1 (SPINK 1) gene is known to be strongly associated with pancreatitis. Patients with these underlying genetic mutations can have severe diseases with a high morbidity rate and frequent hospitalization. We report an Arab girl who presented with acute pancreatitis at the age of 7 years progressing to recurrent chronic pancreatitis over a few years. She had severe obesity from the age of 4 years and developed type 2 diabetes at the age of 12. She had a normal biliary system anatomy. Genetic analysis showed that she had combined heterozygous mutations in the SPINK1 gene (SPINK1, c.101A>G p.(Asn34Ser) and SPINK1, c.56-37T>C). Her parents were first-degree cousins, but neither had obesity. Mother was detected to have the same mutations. She had type 2 diabetes but never presented with pancreatitis. This case is the first to be reported from the Arab region with these combined mutations leading to recurrent chronic pancreatitis. It illustrates the importance of diagnosing the underlying genetic mutation in the absence of other known causes of pancreatitis. Considering the absence of pancreatitis history in the mother who did not have obesity but harboured the same mutations, we point out that severe obesity might be a triggering factor of pancreatitis in the presence of the mutations in SPINK1 gene in this child. While this is not an assumption from a single patient, we show that not all carriers of this mutation develop the disease even within the same family. Triggering factors like severe obesity might have a role in developing the disease. LEARNING POINTS: Acute recurrent pancreatitis and chronic pancreatitis are uncommon in children but might be underdiagnosed. Biliary tract anomalies and dyslipidaemias are known causative factors for pancreatitis, but pancreatitis can be seen in children with intact biliary system. Genetic diagnosis should be sought in children with pancreatitis in the absence of known underlying predisposing factors. SPINK1 mutations can predispose to an early-onset severe recurrent pancreatitis and acute pancreatitis.