Exploring the Genetic Journey; a case of Hereditary Pancreatitis

Dr.Rithwik Sunil, Dr.Bhanu Vikraman pillai , Dr.RekhaHari, Dr. Anupa Thomas , Dr. C Jayakumar
 
 
Eleven year old child presented with abdominal pain, high grade fever and multiple episodes of vomiting since 1 day. 
He was dehydrated
Child was previously admitted with acute pancreatitis in 2019 and Feb 2023.
 
Except for those 2 admissions there is no other admission and in the family also there is history of 
At Aims he was dehydrated with severe abdominal pain mostly in the Right hypochondrium 
He was obese with acanthosis 
Weight:48.2kg(Between 2 & 3 SD)
Height:152cm( less than -3SD)
 
 
 
 
Differentials considered at this junction were:
Anicteric hepatitis
Acute cholecystitis 
Acute gastritis 
GER 
Chronic Pancreatitis 
Obstructive Pancreatic duct(? Pancreatic divisum)
Autoimmune Pancreatitis
 
 
 
Investigations
CBC done showed normal counts with neutrophlicpredominance
USG abdomen showed bulky pancreas with no calcification or peripancreatic fluid.
Presence of Grade 1 fatty liver noted
 
Labs Lipase3810 IU/L
LFT/RFT normal.
Fasting Lipid profile done was normal.
Fecal Elastase : 47
MRCP done showed no structural abnormality
 
ANA IFA was sent was normal
IgG4 subclass was also normal
WES(Whole Exome Sequencing) try
Pathogenic Mutation in PRSS1 in Exon 2 causing Hereditary Pancreatitis
 
 
Treatment
Child was started on IV fluids and IV analgesics other symptomatic medicines and was advised diet control.
Parents were counseled about the condition and educated about the recurrence of this condition in the future.
Child was stable at the time of discharge.
 
Hereditary Pancreatitis
 
 
1. Hereditary pancreatitis (HP) is an autosomal dominant genetic disorder of the pancreas with incomplete penetrance.  
2. HP presents with acute pancreatitis in early adolescence with a high rate of progression to chronic pancreatitis (CP) early adulthood.  
3. Genetically, HP is generally caused gain-of-function mutations in the cationic trypsinogen gene (PRSS1) .
4. A lifetime of pancreatic injury and inflammation increases the risk for the most adverse late complication of HP – pancreatic cancer. 
5. Patients with HP should be closely evaluated for pancreatic endocrine and exocrine insufficiency, counseled on lifestyle changes that may reduce severity and progression, and may be evaluated for total pancreatectomy with islet autotransplantation (TP-IAT) when chronic pain does not respond to therapeutic interventions.
 
6. The pathogenesis of hereditary pancreatitis iscaused mutations in the cationic trypsinogen gene (PRSS1).  
7. Trypsinogen is the zymogen precursor to trypsin, a serine protease that hydrolyzes peptide bonds following an arginine or lysine, preferably in the small intestine.  
8. Two gain-of-function mutations were identified, the first being R122H and the second, N29I .
 
Once the diagnosis is established, the focus is on minimizing recurrence and complications.  
A low fat diet in the form of multiple small meals a day and good hydration is often recommended but remains unproven.  Stress reduction with activities such as running has been reported to be of major benefit in some patients .
 
Take home message;
It is important to monitor these children forassessment of growth and nutritional status with serial plotting of height, weight, and body mass index on growth charts as well as tracking of pubertal development. 
They should also be screened for exocrine and endocrine pancreatic insufficiency.
They should also be advised about proper dietary practices and should also be regularly checked for fat soluble vitamin deficiencies.