Hereditary Pancreatitis
Trypsinogen Gene Mutations

Hereditary Pancreatitis is a rare genetic condition characterized by recurrent episodes of acute pancreatitis attacks. In about half of these cases the problem progresses to chronic pancreatitis, which is severe scarring of the pancreas. Symptoms of an acute attack include abdominal pain, nausea, and vomiting. Laboratory test during an attack usually detect high blood levels of amylase and lipase, which are enzymes released from the pancreas. The first attack typically occurs within the first two decades of life but can begin at any age. In the United States, it is estimated that at least 1,000 individuals are affected with hereditary pancreatitis.


At this time, there is no cure for HP. Treating the symptoms associated with HP is the choice method of medical management. Patients may be prescribed pancreatic enzyme supplements to treat maldigestion, insulin to treat diabetes, analgesics and narcotics to control pain, and lifestyle changes to reduce the risk of pancreatic cancer (for example, NO SMOKING!).

Dietary recommendations to help control pain with digestion include the consumption of small meals throughout the day that are high in carbohydrates and low in protein and fat. Pancreatic enzymes such as Creon, Pancrease, and Violiase are helpful in providing improved digestion and a reduction in diarrhoea and pain for some patients with more advanced disease.

Exposure to smoking and alcohol are known to dramatically increase the risk for pancreatic attacks among individuals with HP. Smoking is strongly discouraged as it doubles the risk for pancreatic cancer. Similarly, alcohol consumption is not recommended for these patients because alcohol is a known risk factor for both acute and chronic pancreatitis. Therefore it is recommended that all HP patients avoid smoking and alcohol consumption.


HP is a genetic disorder, which means that it is usually passed from one generation to the next.

The symptoms of HP are caused by a change to a specific gene. Genes are the packages of information that control how our bodies look and function. A single gene appears to be involved in 60-75% of hereditary pancreatitis families. This gene produces the "cationic trypsinogen" enzyme, which breaks down the proteins present in the foods we eat. (In some research papers cationic trypsinogen is called PRSS1).

When a change to a gene occurs, the gene may no longer function properly. These gene changes are called mutations. Currently, there are two common, and more that 6 uncommon cationic trypsinogen gene mutations that are associated with hereditary pancreatitis. The major mutations are known as cationic trypsinogen "R122H", "N29I".

Families with HP might carry one of these mutations, but usually not more than one type of mutation. It is also possible that a family with a strong history of HP may not carry any of the currently known mutations. For this reason, it is believed that additional genes and mutations that cause HP are awaiting discovery. (Every concerned person is encouraged to join ongoing research studies through the University of Pittsburgh 1-888-PITT DNA, or an affiliated medical centre)


HP symptoms can develop at any age, but most patients have their first pancreatic attack before the age of 20. In addition, there is a great deal of variability in the frequency and severity of pancreatic attacks. Some affected relatives may only have a few episodes of pain, while others in the same family experience more severe symptoms. The cause for this variation in symptoms is unknown.

Individuals who have inherited either the R122H or the N29I mutation have an 80% risk of developing clinical symptoms of HP over the course of their lifetime. Although the remaining 20% of these mutation carriers do not show any symptoms, it is important to remember that they still have a risk of having a child who inherits their HP mutation and is affected with HP.

Much less is known about the other mutations, and it is believed that are rare in the population. Without additional knowledge about these mutations, it is not possible to predict how many people will eventually develop symptoms of pancreatitis.


All of our genes come in pairs. We inherit one set of genes from each of our parents. Hereditary pancreatitis is inherited in a dominant manner, which means that only one copy of the HP gene needs to have a mutation in order for an individual to become affected with HP.

When a parent carries an HP mutation in one of their genes, then each child has a 50% (or 1 in 2) chance of inheriting that mutation. It is important to remember that this risk to inherit an HP mutation is 50% for each pregnancy. The risk to have an affected child is actually less than 50% (it is approximately 40%) since one out of five individuals with the R122H or N29I mutation remain symptom-free over their lifetime.