New Genetic Test Revolutionizes Diagnosis of Hereditary Pancreatitis

A groundbreaking genetic test developed at the Mayo Clinic is transforming how healthcare providers diagnose and manage hereditary pancreatitis. This condition, characterized by inflammation of the pancreas, can lead to chronic pain, frequent hospitalizations, and severe complications such as diabetes, kidney failure, and pancreatic cancer. The new gene panel, known as the Mayo ID: PANGP, is the result of collaborative efforts among scientists, clinicians, and genetic counselors at the clinic.

Pancreatitis presents diagnostic challenges due to its various forms, which can be acute, recurrent, or chronic. In many instances, the underlying cause remains unclear. Symptoms typically include abdominal pain, fever, nausea, rapid pulse, and unintended weight loss. According to the Institute for Health Metrics and Evaluation, approximately 2.75 million new cases of pancreatitis were diagnosed globally in 2021, bringing the total to 5.9 million cases when existing ones are included.

Genetic factors are among the many potential causes of pancreatitis. “When we can’t find a clear cause, genetic testing becomes key,” stated Motaz Ashkar, M.B.B.S., a gastroenterologist at Mayo Clinic. The new panel expands the previous test from four to nine genes, reflecting the latest research and clinical insights.

Unlike many commercial tests that include numerous genes, Mayo’s panel is intentionally focused. “There’s a mindset in genetic testing that bigger is better,” noted Linda Hasadsri, M.D., Ph.D., a clinical molecular geneticist at Mayo Clinic. “But if you include genes with weak or unproven associations, you risk giving patients results that are confusing or meaningless.” The panel comprises established genes such as PRSS1, SPINK1, CFTR, and CTRC, along with newer additions like CPA1, CASR, and CLDN2, which are increasingly recognized for their roles in pancreatitis and pancreatic cancer risk.

The test employs whole exome sequencing, which examines all disease-causing genes in an individual’s DNA. This method allows for a comprehensive analysis of the coding regions across the genome. However, some genes, particularly PRSS1, present testing challenges. “PRSS1 is the most common cause of hereditary pancreatitis worldwide, especially in children,” Dr. Hasadsri explained. “But it’s notoriously difficult to test accurately, leading to many false positives and negatives from other labs.”

To mitigate these issues, Mayo Clinic developed a custom assay with multiple supplementary methods to confirm results and prevent misdiagnosis. The laboratory has also integrated reflex testing capabilities, meaning that if a provider orders the panel and results are inconclusive, further testing can occur without requiring a new sample or additional billing.

The clinical implications of this genetic test are significant. A positive result can clarify a patient’s symptoms and guide treatment options while informing cancer surveillance strategies. “If someone has a PRSS1 pathogenic mutation, their risk of pancreatic cancer is higher,” Dr. Ashkar noted. “We can start monitoring them earlier and more frequently.”

Moreover, the test enables family screening. If a patient tests positive, relatives—even those without symptoms—can be screened. “That allows for early intervention and lifestyle changes that could prevent disease progression,” Dr. Hasadsri added. Even negative results carry weight, as they can rule out hereditary causes, thus alleviating unnecessary anxiety and testing.

Looking ahead, the team at Mayo Clinic is considering the development of a polygenic risk score test for pancreatitis. This would evaluate multiple risk factors to provide a comprehensive risk assessment for the disease. As the understanding of genetic contributions to pancreatitis continues to evolve, this innovative testing approach promises to enhance patient care significantly.