@herstein.jacob @Ahmed7
It’s the only card i could find about hereditary pancreatitis and it’s very different from AMBOSS and UTD (i dont have step1 UW access or FA24)
I think some major changes should be done here
FA24 mentions SPINK1 mutations but nothing really about hereditary pancreatitis from what I can see
Step 1 UWorld QID 433 tests this by saying what would happen if trypsin could not be inactivated, answer = pancreatitis
“Serine peptidase inhibitor Kazal-type 1 (SPINK1) is secreted by pancreatic
acinar cells and functions as a trypsin inhibitor. It impedes the activity of
trypsinogen molecules that become prematurely activated within the pancreas.”
“Hereditary pancreatitis is a rare disorder that results from mutations involving the trypsinogen or SPINK1 gene. The most common mutation leads to the production of abnormal trypsin that is not susceptible to inactivating cleavage by trypsin.
Because a small amount of trypsinogen normally activates prematurely within the pancreatic acini and ducts, these protective mechanisms are critical for preventing recurrent attacks of acute pancreatitis.”
Educational objective “Educational objective:
Multiple inhibitory mechanisms exist to prevent premature activation of trypsinogen before it reaches the duodenal lumen, including cleavage inactivation of trypsin by trypsin itself and production of trypsin inhibitors (eg, SPINK1). Gene mutations that render trypsin insensitive to cleavage inactivation cause hereditary pancreatitis.”
@mohannadkh10 you have to let us know what the question was, how was it tested, why was the original card not sufficient? Why does “PRSS1” need to be added?
This is the question
A 12-year-old girl is brought to the physician because of a 2-hour history of severe epigastric pain, nausea, and vomiting. Her father has a history of similar episodes of abdominal pain and developed diabetes mellitus at the age of 30 years. Abdominal examination shows guarding and rigidity. Ultrasonography of the abdomen shows diffuse enlargement of the pancreas; no gallstones are visualized. Which of the following is the most likely underlying cause of this patient’s condition?
Defective bilirubin glucuronidation
Elevated serum amylase levels
Premature activation of trypsinogen
Defective elastase inhibitor
Impaired cellular copper transport
Why does PRSS1 should be added?
Because it’s the most common mutation causing HP
here is a text from the explanation " . [Hereditary pancreatitis]), which this patient most likely has, is usually caused by a mutated [PRSS1] gene that promotes intrapancreatic trypsinogen activation. Other genetic variants associated with chronic pancreatitis are mutations in SPINK 1 and CFTR genes."
The idea of premature activation of trypsinogen (answer in amboss q, also found in the educational objective in UW) is mentioned between the lines in the original card and I believe more focus should be added to it
The other thing I would like to change in the original card is to add something that can help us suspect HP (age and family hx, autosomal dominant most of the time) this is only because this is the only card about HP
The change I suggested doesn’t need to be the final one
I am suggesting turning the focus of the card from the etiology and gene mutations to the pathophysiology and clinical presentation
The question you mentioned did not mention any gene so I don’t think we need to change the gene that is closed;. It won’t help you get the question right IMO. I agree that changing the closes to better test the result of having a mutation that leads to too much trypsin is better
We can change to
“Hereditary pancreatitis is an autosomal dominant condition that leads to premature activation of {{c1::trypsinogen}} leading to recurrent bouts of pancreatitis in childhood” if needed, can add at the end of text ;due to SPINK1 mutations
Extra
- Caused by mutations in PRSS1 (most commonly) and SPINK1
I don’t think including a close on SPINK1 or PRSS1 is even necessary. Unless someone has done a question where that was the answer
Note that AMBOSS only says auto dominant for the PRSS1 gene AFAI can see
I agree with you on the part that there is no need to add a cloze for the gene mutation (we can add it in the extra)
Here is part of UTD article " Hereditary pancreatitis is an autosomal dominant disorder that accounts for a small fraction of cases of chronic pancreatitis. Autosomal dominant hereditary pancreatitis is most often associated with mutations in serine protease 1 gene (PRSS1 ) on chromosome 7q35, which encodes cationic trypsinogen. Rarely, autosomal dominant-appearing hereditary pancreatitis is identified in a kindred that does not have an identifiable PRSS1 mutation"
They said it’s autosomal dominant in the definition
Another thing i like to suggest is to add in the extra that it’s a risk factor for pancreatic cancer (i saw it in UW step2 tables) (mentioned in 14940, 3585 table)
Appreciate the good discussion here - would prefer something like @Ahmed7 version where we shift focus to the mechanism rather than specific mutation. Don’t think it is always AD, I believe SPINK1 is AR inheritance based on google searches.
Also, no need to add cancer risk - chronic pancreatitis as a risk for carcinoma is already very well-covered in the deck
“Hereditary” pancreatitis should be enough of a hint. So we can remove AD
This change can make you answer both the AMBOSS and UWorld question which covers step 1 and step 2.
The gene mutations can be in extra since AMBOSS & UWorld both are not making this the focus of their questions
Think it might make more sense to say “caused by” rather than “leads to” because the clinical condition is a result of the enzyme activation. Semantics, but I think the wording matters.
“Leads to” implies: hereditary pancreatitis (cause not specified) → enzyme activation → recurrent pancreatitis
“Caused by” implies: enzyme activation → hereditary pancreatitis
@Anking-Maintainers
Think we should close this one
support, if @mohannadkh10 comment above gets 5 likes we can push