Early-onset pancreatitis linked to genetics, family history in children

In children, mutations in cationic trypsinogen (PRSS1) and in chymotrypsin C (CTRC), as well as a family history are strongly associated with early-onset pancreatitis, especially in those less than 6 years old, while those with later-onset disease are more likely to have non-genetic risk factors, according to study results published in the Journal of Pediatrics.

“It’s widely known that alcohol and smoking are easily identifiable risk factors in adults who develop pancreatitis,” said Matthew Giefer, MD, director of gastrointestinal endoscopy, Seattle Children’s Hospital, Seattle, WA. “However, determining the underlying causes of the disease in children has been challenging to uncover. This study allowed us to test and evaluate the association between age of onset and characteristics of patients with acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP).”

In this study, Dr. Giefer and fellow researchers sought to determine whether age of onset of pediatric ARP or CP was associated with unique features or disease course. From INSPPIRE (International Study Group of Pediatric Pancreatitis: In Search for a CuRE) centers, they gathered data for 342 children with ARP or CP between September 2012 and March 2016.

INSPPIRE is the nation’s first and only multicenter, National Institutes of Health-funded pediatric pancreatitis registry.

Of these children, 38% (n=129) were less than 6 years old at the time of first diagnosis of ARP, 32% (n=111) were aged 6 to 11 years, and 30% (n=102) were age 12 or older.

Their most significant findings were in the youngest cohort—patients aged 5 years and younger—with early-onset pancreatitis. A full 71% had at least one pancreatitis-associated gene mutation, a significantly larger proportion than in those with later-onset pancreatitis. PRSS1 mutations were found in 43% of patients, and CTRC mutations in 14%.

Using the Cochran-Armitage trend test and Jonckheere-Terpstra test, Dr. Giefert and colleagues assessed differences between the age groups, and found that the following factors were associated with early-onset disease:

• Mutations in cationic trypsinogen (PRSS1; P < 0.01);
• Mutations in chymotrypsin C (CTRC; P=0.01);
• Family history of acute pancreatitis (P=0.02); family history of CP (P < 0.01);
• The presence of biliary cysts (P=0.04); and
• Chronic renal failure (P=0.02).

These researchers also found that later-onset disease was more likely in patients with:

• Hypertriglyceridemia (P=0.04);
• Ulcerative colitis (P=0.02);
• Autoimmune diseases (P < 0.0001); or
• Medication use (P < 0.01).

Dr. Giefer and colleagues also found that patients with later-onset disease were more likely to have visits to the emergency department (P < 0.05) and to have diabetes (P < 0.01).

“Building upon previous data related to the PRSS1 mutations found in patients with early-onset pancreatitis, we learned that combined with our current data, patients with PRSS1 are more likely to have an aggressive disease course,” said Dr. Giefer. “The more we understand and discover important details such as this, the closer we are to developing treatments that could modify the disease course in patients.”

He now plans further research on disease course, treatment responses, and outcomes, as well as whether these are dependent on the age of a first pancreatitis attack in children.

“Overall, this research sheds light on a disease that not only affects adults, but an increasing number of children. The findings provide us with an improved understanding of the genetic factors involved in early-onset pancreatitis, which will help the pediatric community to improve the evaluation and treatment process for patients,” Dr. Giefer concluded.