Centre de référence
des maladies rares
du pancréas

Hereditary Pancreatitis Relateed To PRSS1 Mutations

What is PRSS1-related hereditary pancreatitis?

Chronic pancreatitis of genetic origin due to mutations of the PRSS1 gene (serine protease 1) which codes for cationic trypsinogen. Transmission is autosomal dominant, penetrance is high but incomplete (> 80%). Prevalence is 6/100,000.

The mutation provokes an alteration of a self-cleavage site of the trypsin molecule. As it accumulates, trypsin activates the pancreatic enzymatic cascade in an early, unsuitable manner around the acinar cells, thus provoking repeated, acute pancreatitis.

How is it diagnosed ?

Two circumstances are evocative: young age at the start of symptoms or a family history of pancreatitis.

An analysis for mutation of the PRSS1 gene is performed after the patient's written consent is obtained.

What is its specific treatment ?

There is no specific treatment for chronic hereditary pancreatitis. In particular, there is no gene therapy. Treatments are above all symptomatic (pain care) and related to complications. In all cases, treatments must be multi-disciplinary, and social and psychological dimensions must always be taken into account.

Medical treatment is above all symptomatic, and the whole range of analgesics for WHO steps 1, 2 or 3 must be used as needed. However, care must be taken in case of long-term use of opioids (chronic usage > 6 months). They are thus of limited interest, and there is a real risk of dependence and social withdrawal (particularly in teenage patients). All alternatives must thus be envisaged: relaxation therapy, hypnosis, treatments of neuropathic pain (pregabalin, etc.), antidepressants, feeding exclusively by tube for four weeks during inflammatory phases in order to break the pain cycle, endoscopy, surgery, etc. It is essential:

- to obtain suitable health and diet advice to minimise the risk of flare-ups: to stop smoking, limit alcohol consumption, follow a balanced diet with limited consumption of cooked fats (fried foods, etc.) ;

- take an annual test for diabetes, exocrine pancreatic insufficiency and cholestasis. The risk of occurrence of pancreatic adenocarcinoma is increased with PRSS-related hereditary pancreatitis, in particular in smokers. This justifies testing starting at age 40 with an annual MRI of the pancreas..