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Hereditary pancreatitis(PCTT)

MedGen UID:
116056
Concept ID:
C0238339
Disease or Syndrome
Synonyms: Hereditary chronic pancreatitis; PCTT
SNOMED CT: Hereditary pancreatitis (68072000); Familial chronic pancreatitis (235956004); Hereditary chronic pancreatitis (235956004)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): CFTR (7q31.2); CTRC (1p36.21); PRSS1 (7q34); PRSS2 (7q34); SPINK1 (5q32)
 
Monarch Initiative: MONDO:0008185
OMIM®: 167800
Orphanet: ORPHA676

Definition

PRSS1-related hereditary pancreatitis (HP) is characterized by episodes of acute pancreatitis (AP) and recurrent acute pancreatitis (RAP: >1 episode of AP), with frequent progression to chronic pancreatitis (CP). Manifestations of acute pancreatitis can range from vague abdominal pain lasting one to three days to severe abdominal pain lasting days to weeks and requiring hospitalization. [from GeneReviews]

Additional description

From MedlinePlus Genetics
Hereditary pancreatitis is a genetic condition characterized by recurrent episodes of inflammation of the pancreas (pancreatitis). The pancreas produces enzymes that help digest food, and it also produces insulin, a hormone that controls levels of blood glucose, also called blood sugar. Episodes of pancreatitis can lead to permanent tissue damage and loss of pancreatic function.

Signs and symptoms of this condition usually begin in late childhood with an episode of acute pancreatitis. A sudden (acute) attack can cause abdominal pain, fever, nausea, or vomiting. An episode typically lasts from one to three days, although some people may experience severe episodes that last longer. Hereditary pancreatitis progresses to recurrent acute pancreatitis with multiple episodes of acute pancreatitis that recur over a period of at least a year; the number of episodes a person experiences varies. Recurrent acute pancreatitis leads to chronic pancreatitis, which occurs when the pancreas is persistently inflamed. Chronic pancreatitis usually develops by early adulthood in affected individuals. Signs and symptoms of chronic pancreatitis include occasional or frequent abdominal pain of varying severity, flatulence, and bloating. Many individuals with hereditary pancreatitis also develop abnormal calcium deposits in the pancreas (pancreatic calcifications) by early adulthood.

Years of inflammation damage the pancreas, causing the formation of scar tissue (fibrosis) in place of functioning pancreatic tissue. Pancreatic fibrosis leads to the loss of pancreatic function in many affected individuals. This loss of function can impair the production of digestive enzymes and disrupt normal digestion, leading to fatty stool (steatorrhea), weight loss, and protein and vitamin deficiencies. Because of a decrease in insulin production due to a loss of pancreatic function, about a quarter of individuals with hereditary pancreatitis will develop type 1 diabetes mellitus by mid-adulthood; the risk of developing diabetes increases with age.

Chronic pancreatic inflammation and damage to the pancreas increase the risk of developing pancreatic cancer. The risk is particularly high in people with hereditary pancreatitis who also smoke, use alcohol, have type 1 diabetes mellitus, or have a family history of cancer. In affected individuals who develop pancreatic cancer, it is typically diagnosed in mid-adulthood.

Complications from pancreatic cancer and type 1 diabetes mellitus are the most common causes of death in individuals with hereditary pancreatitis, although individuals with this condition are thought to have a normal life expectancy.  https://medlineplus.gov/genetics/condition/hereditary-pancreatitis

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Pancreatic pseudocyst
MedGen UID:
18280
Concept ID:
C0030299
Disease or Syndrome
Cyst-like space not lined by epithelium and contained within the pancreas. Pancreatic pseudocysts are often associated with pancreatitis.
Steatorrhea
MedGen UID:
20948
Concept ID:
C0038238
Finding
Greater than normal amounts of fat in the feces. This is a result of malabsorption of lipids in the small intestine and results in frothy foul-smelling fecal matter that floats.
Exocrine pancreatic insufficiency
MedGen UID:
75647
Concept ID:
C0267963
Disease or Syndrome
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
Pancreatic calcification
MedGen UID:
330843
Concept ID:
C1842406
Finding
The presence of abnormal calcium deposition lesions in the pancreas.
Abnormal thrombosis
MedGen UID:
871247
Concept ID:
C4025731
Anatomical Abnormality
Venous or arterial thrombosis (formation of blood clots) of spontaneous nature and which cannot be fully explained by acquired risk (e.g. atherosclerosis).
Pleural effusion
MedGen UID:
10805
Concept ID:
C0032227
Disease or Syndrome
The presence of an excessive amount of fluid in the pleural cavity.
Pancreatitis
MedGen UID:
14586
Concept ID:
C0030305
Disease or Syndrome
The presence of inflammation in the pancreas.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.

Professional guidelines

PubMed

Fu Y, Lucas AL
Gastrointest Endosc Clin N Am 2022 Jan;32(1):27-43. doi: 10.1016/j.giec.2021.08.006. PMID: 34798985
Goggins M, Overbeek KA, Brand R, Syngal S, Del Chiaro M, Bartsch DK, Bassi C, Carrato A, Farrell J, Fishman EK, Fockens P, Gress TM, van Hooft JE, Hruban RH, Kastrinos F, Klein A, Lennon AM, Lucas A, Park W, Rustgi A, Simeone D, Stoffel E, Vasen HFA, Cahen DL, Canto MI, Bruno M; International Cancer of the Pancreas Screening (CAPS) consortium
Gut 2020 Jan;69(1):7-17. Epub 2019 Oct 31 doi: 10.1136/gutjnl-2019-319352. PMID: 31672839Free PMC Article
Singh VK, Yadav D, Garg PK
JAMA 2019 Dec 24;322(24):2422-2434. doi: 10.1001/jama.2019.19411. PMID: 31860051

Curated

UK NICE Guideline NG104, Pancreatitis, 2020

Recent clinical studies

Etiology

Klein AP
Nat Rev Gastroenterol Hepatol 2021 Jul;18(7):493-502. Epub 2021 May 17 doi: 10.1038/s41575-021-00457-x. PMID: 34002083Free PMC Article
Singh VK, Yadav D, Garg PK
JAMA 2019 Dec 24;322(24):2422-2434. doi: 10.1001/jama.2019.19411. PMID: 31860051
Mayerle J, Sendler M, Hegyi E, Beyer G, Lerch MM, Sahin-Tóth M
Gastroenterology 2019 May;156(7):1951-1968.e1. Epub 2019 Jan 18 doi: 10.1053/j.gastro.2018.11.081. PMID: 30660731Free PMC Article
Hasan A, Moscoso DI, Kastrinos F
Gastrointest Endosc Clin N Am 2018 Oct;28(4):587-603. doi: 10.1016/j.giec.2018.06.001. PMID: 30241646
Uretsky G, Goldschmiedt M, James K
Am Fam Physician 1999 May 1;59(9):2507-12. PMID: 10323357

Diagnosis

Klein AP
Nat Rev Gastroenterol Hepatol 2021 Jul;18(7):493-502. Epub 2021 May 17 doi: 10.1038/s41575-021-00457-x. PMID: 34002083Free PMC Article
Singh VK, Yadav D, Garg PK
JAMA 2019 Dec 24;322(24):2422-2434. doi: 10.1001/jama.2019.19411. PMID: 31860051
Hasan A, Moscoso DI, Kastrinos F
Gastrointest Endosc Clin N Am 2018 Oct;28(4):587-603. doi: 10.1016/j.giec.2018.06.001. PMID: 30241646
Lal A, Lal DR
Pediatr Surg Int 2010 Dec;26(12):1193-9. Epub 2010 Aug 10 doi: 10.1007/s00383-010-2684-4. PMID: 20697897
Uretsky G, Goldschmiedt M, James K
Am Fam Physician 1999 May 1;59(9):2507-12. PMID: 10323357

Therapy

Scholten L, Latenstein AE, Aalfs CM, Bruno MJ, Busch OR, Bonsing BA, Koerkamp BG, Molenaar IQ, Ubbink DT, van Hooft JE, Fockens P, Glas J, DeVries JH, Besselink MG; Dutch Pancreatic Cancer Group
United European Gastroenterol J 2020 Oct;8(8):865-877. Epub 2020 Jul 23 doi: 10.1177/2050640620945534. PMID: 32703081Free PMC Article
Singh VK, Yadav D, Garg PK
JAMA 2019 Dec 24;322(24):2422-2434. doi: 10.1001/jama.2019.19411. PMID: 31860051
Rivera Rivera ED, Chugh A, Cordova J, Young S
Pediatr Ann 2016 Feb;45(2):e50-3. doi: 10.3928/00904481-20160115-01. PMID: 26878183
Bruenderman EH, Martin RC 2nd
J Surg Res 2015 Mar;194(1):212-9. Epub 2014 Oct 13 doi: 10.1016/j.jss.2014.06.046. PMID: 25479908Free PMC Article
Lowenfels AB, Maisonneuve P
Jpn J Clin Oncol 2004 May;34(5):238-44. doi: 10.1093/jjco/hyh045. PMID: 15231857

Prognosis

Singh VK, Yadav D, Garg PK
JAMA 2019 Dec 24;322(24):2422-2434. doi: 10.1001/jama.2019.19411. PMID: 31860051
Mayerle J, Sendler M, Hegyi E, Beyer G, Lerch MM, Sahin-Tóth M
Gastroenterology 2019 May;156(7):1951-1968.e1. Epub 2019 Jan 18 doi: 10.1053/j.gastro.2018.11.081. PMID: 30660731Free PMC Article
Rustgi AK
Genes Dev 2014 Jan 1;28(1):1-7. doi: 10.1101/gad.228452.113. PMID: 24395243Free PMC Article
Lal A, Lal DR
Pediatr Surg Int 2010 Dec;26(12):1193-9. Epub 2010 Aug 10 doi: 10.1007/s00383-010-2684-4. PMID: 20697897
Uretsky G, Goldschmiedt M, James K
Am Fam Physician 1999 May 1;59(9):2507-12. PMID: 10323357

Clinical prediction guides

Singh VK, Yadav D, Garg PK
JAMA 2019 Dec 24;322(24):2422-2434. doi: 10.1001/jama.2019.19411. PMID: 31860051
Mayerle J, Sendler M, Hegyi E, Beyer G, Lerch MM, Sahin-Tóth M
Gastroenterology 2019 May;156(7):1951-1968.e1. Epub 2019 Jan 18 doi: 10.1053/j.gastro.2018.11.081. PMID: 30660731Free PMC Article
Whitcomb DC, Shelton CA, Brand RE
Gastroenterology 2015 Oct;149(5):1252-1264.e4. Epub 2015 Aug 6 doi: 10.1053/j.gastro.2015.07.057. PMID: 26255042
Malats N
Pancreatology 2001;1(5):472-6. doi: 10.1159/000055850. PMID: 12120227
Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD
Nat Genet 1996 Oct;14(2):141-5. doi: 10.1038/ng1096-141. PMID: 8841182

Recent systematic reviews

Gandhi S, de la Fuente J, Murad MH, Majumder S
Clin Transl Gastroenterol 2022 Mar 28;13(3):e00463. doi: 10.14309/ctg.0000000000000463. PMID: 35142721Free PMC Article
Scholten L, Latenstein AE, Aalfs CM, Bruno MJ, Busch OR, Bonsing BA, Koerkamp BG, Molenaar IQ, Ubbink DT, van Hooft JE, Fockens P, Glas J, DeVries JH, Besselink MG; Dutch Pancreatic Cancer Group
United European Gastroenterol J 2020 Oct;8(8):865-877. Epub 2020 Jul 23 doi: 10.1177/2050640620945534. PMID: 32703081Free PMC Article
Bruenderman EH, Martin RC 2nd
J Surg Res 2015 Mar;194(1):212-9. Epub 2014 Oct 13 doi: 10.1016/j.jss.2014.06.046. PMID: 25479908Free PMC Article
Mekitarian Filho E, Carvalho WB, Silva FD
J Pediatr (Rio J) 2012 Mar-Apr;88(2):101-14. doi: 10.2223/JPED.2163. PMID: 22543443

Supplemental Content

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    • PubMed
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      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2020
      UK NICE Guideline NG104, Pancreatitis, 2020

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