Pancreatic agenesis: Year of the Zebra 2026

Pancreatic agenesis is an extremely rare condition where part or all of the pancreas fails to develop before birth. The pancreas is an elongated organ located in the posterior abdominal wall, lying mostly behind the stomach.

It has several different parts, including the head, uncinate process (a hook-shaped aspect of the organ that curves back toward the body from the head), neck, body, and tail.

The pancreas functions both as an exocrine gland, secreting pancreatic juices into the duodenum to help with digestion; and an endocrine gland, secreting the hormones insulin and glucagon directly into the bloodstream to regulate blood sugar metabolism.

Normally, around the 4th to 5th weeks of fetal development, the pancreas forms from two tiny buds that emerge from the primitive gut tube, called the dorsal and ventral pancreatic buds.

These buds eventually fuse together and mature into the fully formed pancreas.

In people with pancreatic agenesis, development doesn’t go as planned, so part or all of the pancreas doesn’t develop completely.

Even though there are only around 100 cases of pancreatic agenesis described in the literature, researchers have found several cases are linked to mutations in genes that guide pancreatic formation, especially the PDX1 gene, sometimes called the “master regulator” of pancreatic development.

Mutations in other genes like PTF1A, GATA6, and GATA4 can also disrupt pancreatic formation. Some of these mutations affect only the pancreas, while some mutations can cause additional abnormalities involving the heart, intestines, gallbladder, or nervous system.

Now, most cases of pancreatic agenesis involve the dorsal portion of the pancreas, which normally develops into the body and tail, where most of the insulin-producing cells are located.

As a result, individuals often develop diabetes very early in life. Patients with complete pancreatic agenesis might even first present with severe neonatal diabetes.

High blood sugar levels in infants can cause dehydration, frequent urination, vomiting, and poor feeding.