Hereditary pancreatitis pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
Line 10: Line 10:
Pancreatitis associated with a known germline pathogenic variant.<ref name="pmid11030605">{{cite journal |vauthors=Whitcomb DC, Ulrich CD |title=Hereditary pancreatitis: new insights, new directions |journal=Baillieres Best Pract Res Clin Gastroenterol |volume=13 |issue=2 |pages=253–63 |year=1999 |pmid=11030605 |doi= |url=}}</ref>
Pancreatitis associated with a known germline pathogenic variant.<ref name="pmid11030605">{{cite journal |vauthors=Whitcomb DC, Ulrich CD |title=Hereditary pancreatitis: new insights, new directions |journal=Baillieres Best Pract Res Clin Gastroenterol |volume=13 |issue=2 |pages=253–63 |year=1999 |pmid=11030605 |doi= |url=}}</ref>


===Pathogenesis===
=== Pathogenesis: ===
 
==== Abnormal regulation of trypsin: ====
*
 
===Mode of inheritance:===
*Hereditary pancreatitis involves atleast 3 different patterns of inheritance:<ref name="pmid8964426">{{cite journal |vauthors=Whitcomb DC, Preston RA, Aston CE, Sossenheimer MJ, Barua PS, Zhang Y, Wong-Chong A, White GJ, Wood PG, Gates LK, Ulrich C, Martin SP, Post JC, Ehrlich GD |title=A gene for hereditary pancreatitis maps to chromosome 7q35 |journal=Gastroenterology |volume=110 |issue=6 |pages=1975–80 |year=1996 |pmid=8964426 |doi= |url=}}</ref><ref name="pmid8841182">{{cite journal |vauthors=Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD |title=Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene |journal=Nat. Genet. |volume=14 |issue=2 |pages=141–5 |year=1996 |pmid=8841182 |doi=10.1038/ng1096-141 |url=}}</ref><ref name="pmid9322498">{{cite journal |vauthors=Gorry MC, Gabbaizedeh D, Furey W, Gates LK, Preston RA, Aston CE, Zhang Y, Ulrich C, Ehrlich GD, Whitcomb DC |title=Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis |journal=Gastroenterology |volume=113 |issue=4 |pages=1063–8 |year=1997 |pmid=9322498 |doi= |url=}}</ref><ref name="pmid15017610">{{cite journal |vauthors=Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP |title=Clinical and genetic characteristics of hereditary pancreatitis in Europe |journal=Clin. Gastroenterol. Hepatol. |volume=2 |issue=3 |pages=252–61 |year=2004 |pmid=15017610 |doi= |url=}}</ref><ref name="pmid19407482">{{cite journal |vauthors=LaFemina J, Roberts PA, Hung YP, Gusella JF, Sahani D, Fernández-del Castillo C, Warshaw AL, Thayer SP |title=Identification of a novel kindred with familial pancreatitis and pancreatic cancer |journal=Pancreatology |volume=9 |issue=3 |pages=273–9 |year=2009 |pmid=19407482 |pmc=3713708 |doi=10.1159/000201553 |url=}}</ref><ref name="pmid22572128">{{cite journal |vauthors=LaRusch J, Barmada MM, Solomon S, Whitcomb DC |title=Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred |journal=JOP |volume=13 |issue=3 |pages=258–62 |year=2012 |pmid=22572128 |pmc=3651649 |doi= |url=}}</ref><ref name="pmid20977904">{{cite journal |vauthors=Schneider A, Larusch J, Sun X, Aloe A, Lamb J, Hawes R, Cotton P, Brand RE, Anderson MA, Money ME, Banks PA, Lewis MD, Baillie J, Sherman S, Disario J, Burton FR, Gardner TB, Amann ST, Gelrud A, George R, Rockacy MJ, Kassabian S, Martinson J, Slivka A, Yadav D, Oruc N, Barmada MM, Frizzell R, Whitcomb DC |title=Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis |journal=Gastroenterology |volume=140 |issue=1 |pages=162–71 |year=2011 |pmid=20977904 |pmc=3171690 |doi=10.1053/j.gastro.2010.10.045 |url=}}</ref><ref name="pmid22427236">{{cite journal |vauthors=Rosendahl J, Landt O, Bernadova J, Kovacs P, Teich N, Bödeker H, Keim V, Ruffert C, Mössner J, Kage A, Stumvoll M, Groneberg D, Krüger R, Luck W, Treiber M, Becker M, Witt H |title=CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated? |journal=Gut |volume=62 |issue=4 |pages=582–92 |year=2013 |pmid=22427236 |doi=10.1136/gutjnl-2011-300645 |url=}}</ref>
*Hereditary pancreatitis involves atleast 3 different patterns of inheritance:<ref name="pmid8964426">{{cite journal |vauthors=Whitcomb DC, Preston RA, Aston CE, Sossenheimer MJ, Barua PS, Zhang Y, Wong-Chong A, White GJ, Wood PG, Gates LK, Ulrich C, Martin SP, Post JC, Ehrlich GD |title=A gene for hereditary pancreatitis maps to chromosome 7q35 |journal=Gastroenterology |volume=110 |issue=6 |pages=1975–80 |year=1996 |pmid=8964426 |doi= |url=}}</ref><ref name="pmid8841182">{{cite journal |vauthors=Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD |title=Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene |journal=Nat. Genet. |volume=14 |issue=2 |pages=141–5 |year=1996 |pmid=8841182 |doi=10.1038/ng1096-141 |url=}}</ref><ref name="pmid9322498">{{cite journal |vauthors=Gorry MC, Gabbaizedeh D, Furey W, Gates LK, Preston RA, Aston CE, Zhang Y, Ulrich C, Ehrlich GD, Whitcomb DC |title=Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis |journal=Gastroenterology |volume=113 |issue=4 |pages=1063–8 |year=1997 |pmid=9322498 |doi= |url=}}</ref><ref name="pmid15017610">{{cite journal |vauthors=Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP |title=Clinical and genetic characteristics of hereditary pancreatitis in Europe |journal=Clin. Gastroenterol. Hepatol. |volume=2 |issue=3 |pages=252–61 |year=2004 |pmid=15017610 |doi= |url=}}</ref><ref name="pmid19407482">{{cite journal |vauthors=LaFemina J, Roberts PA, Hung YP, Gusella JF, Sahani D, Fernández-del Castillo C, Warshaw AL, Thayer SP |title=Identification of a novel kindred with familial pancreatitis and pancreatic cancer |journal=Pancreatology |volume=9 |issue=3 |pages=273–9 |year=2009 |pmid=19407482 |pmc=3713708 |doi=10.1159/000201553 |url=}}</ref><ref name="pmid22572128">{{cite journal |vauthors=LaRusch J, Barmada MM, Solomon S, Whitcomb DC |title=Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred |journal=JOP |volume=13 |issue=3 |pages=258–62 |year=2012 |pmid=22572128 |pmc=3651649 |doi= |url=}}</ref><ref name="pmid20977904">{{cite journal |vauthors=Schneider A, Larusch J, Sun X, Aloe A, Lamb J, Hawes R, Cotton P, Brand RE, Anderson MA, Money ME, Banks PA, Lewis MD, Baillie J, Sherman S, Disario J, Burton FR, Gardner TB, Amann ST, Gelrud A, George R, Rockacy MJ, Kassabian S, Martinson J, Slivka A, Yadav D, Oruc N, Barmada MM, Frizzell R, Whitcomb DC |title=Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis |journal=Gastroenterology |volume=140 |issue=1 |pages=162–71 |year=2011 |pmid=20977904 |pmc=3171690 |doi=10.1053/j.gastro.2010.10.045 |url=}}</ref><ref name="pmid22427236">{{cite journal |vauthors=Rosendahl J, Landt O, Bernadova J, Kovacs P, Teich N, Bödeker H, Keim V, Ruffert C, Mössner J, Kage A, Stumvoll M, Groneberg D, Krüger R, Luck W, Treiber M, Becker M, Witt H |title=CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated? |journal=Gut |volume=62 |issue=4 |pages=582–92 |year=2013 |pmid=22427236 |doi=10.1136/gutjnl-2011-300645 |url=}}</ref>
{| class="wikitable"
{| class="wikitable"
Line 25: Line 30:
|A combination of genetic and environmental factors
|A combination of genetic and environmental factors
|}
|}
==Genetics==
Hereditary pancreatitis involves mutations in the following genes:


===== Mutations in PRSS1 gene: =====
===== Mutations in PRSS1 gene: =====
Line 36: Line 44:
===== Mutations in other genes: =====
===== Mutations in other genes: =====


==Genetics==
===== Common mutations: =====
* The most common disease associated mutations in PRSS1 gene include:<ref name="pmid8841182">{{cite journal |vauthors=Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD |title=Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene |journal=Nat. Genet. |volume=14 |issue=2 |pages=141–5 |year=1996 |pmid=8841182 |doi=10.1038/ng1096-141 |url=}}</ref><ref name="pmid9322498">{{cite journal |vauthors=Gorry MC, Gabbaizedeh D, Furey W, Gates LK, Preston RA, Aston CE, Zhang Y, Ulrich C, Ehrlich GD, Whitcomb DC |title=Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis |journal=Gastroenterology |volume=113 |issue=4 |pages=1063–8 |year=1997 |pmid=9322498 |doi= |url=}}</ref><ref name="pmid9633818">{{cite journal |vauthors=Teich N, Mössner J, Keim V |title=Mutations of the cationic trypsinogen in hereditary pancreatitis |journal=Hum. Mutat. |volume=12 |issue=1 |pages=39–43 |year=1998 |pmid=9633818 |doi=10.1002/(SICI)1098-1004(1998)12:1<39::AID-HUMU6>3.0.CO;2-P |url=}}</ref>
* The most common disease associated mutations in PRSS1 gene include:<ref name="pmid8841182">{{cite journal |vauthors=Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD |title=Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene |journal=Nat. Genet. |volume=14 |issue=2 |pages=141–5 |year=1996 |pmid=8841182 |doi=10.1038/ng1096-141 |url=}}</ref><ref name="pmid9322498">{{cite journal |vauthors=Gorry MC, Gabbaizedeh D, Furey W, Gates LK, Preston RA, Aston CE, Zhang Y, Ulrich C, Ehrlich GD, Whitcomb DC |title=Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis |journal=Gastroenterology |volume=113 |issue=4 |pages=1063–8 |year=1997 |pmid=9322498 |doi= |url=}}</ref><ref name="pmid9633818">{{cite journal |vauthors=Teich N, Mössner J, Keim V |title=Mutations of the cationic trypsinogen in hereditary pancreatitis |journal=Hum. Mutat. |volume=12 |issue=1 |pages=39–43 |year=1998 |pmid=9633818 |doi=10.1002/(SICI)1098-1004(1998)12:1<39::AID-HUMU6>3.0.CO;2-P |url=}}</ref>
** R122H<ref name="pmid8841182">{{cite journal |vauthors=Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD |title=Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene |journal=Nat. Genet. |volume=14 |issue=2 |pages=141–5 |year=1996 |pmid=8841182 |doi=10.1038/ng1096-141 |url=}}</ref>
** R122H<ref name="pmid8841182">{{cite journal |vauthors=Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD |title=Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene |journal=Nat. Genet. |volume=14 |issue=2 |pages=141–5 |year=1996 |pmid=8841182 |doi=10.1038/ng1096-141 |url=}}</ref>

Revision as of 17:27, 15 January 2018

Hereditary pancreatitis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Hereditary pancreatitis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Guidelines for Management

Case Studies

Case #1

Hereditary pancreatitis pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Hereditary pancreatitis pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Hereditary pancreatitis pathophysiology

CDC on Hereditary pancreatitis pathophysiology

Hereditary pancreatitis pathophysiology in the news

Blogs on Hereditary pancreatitis pathophysiology

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Hereditary pancreatitis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2]

Overview

Pathophysiology

Hereditary pancreatitis is defined as EITHER two or more individuals with pancreatitis in two or more generations of a family (i.e., an autosomal dominant pattern of inheritance) OR Pancreatitis associated with a known germline pathogenic variant.[1]

Pathogenesis:

Abnormal regulation of trypsin:

Mode of inheritance:

Mode of inheritance Genes involved
Autosomal dominant  Serine protease 1 gene (PRSS1)
Autosomal recessive Serine protease inhibitor Kazal type 1 gene (SPINK1, also called pancreatic secretory trypsin inhibitor gene)
Complex genetics A combination of genetic and environmental factors

Genetics

Hereditary pancreatitis involves mutations in the following genes:

Mutations in PRSS1 gene:
Mutations in SPINK1 gene:
Mutations in CFTR  gene:
Mutations in CTRC gene:
Mutations in other genes:
Common mutations:
  • The most common disease associated mutations in PRSS1 gene include:[3][4][10]
    • R122H[3]
    • N29I 
    • A16V
  • Other genes may include:
    • PRSS2, the anionic trypsinogen gene

Associated Conditions

Hereditary pancreatitis may be associated with following syndromes:

  • Shwachman-Diamond syndrome (SDS) 
  • Pearson marrow pancreas syndrome
  • CEL maturity-onset diabetes of the young (CEL-MODY)
  • Johanson-Blizzard syndrome

Gross Pathology

  • On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

  • On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

References

  1. ↑ Whitcomb DC, Ulrich CD (1999). "Hereditary pancreatitis: new insights, new directions". Baillieres Best Pract Res Clin Gastroenterol. 13 (2): 253–63. PMID 11030605.
  2. ↑ Whitcomb DC, Preston RA, Aston CE, Sossenheimer MJ, Barua PS, Zhang Y, Wong-Chong A, White GJ, Wood PG, Gates LK, Ulrich C, Martin SP, Post JC, Ehrlich GD (1996). "A gene for hereditary pancreatitis maps to chromosome 7q35". Gastroenterology. 110 (6): 1975–80. PMID 8964426.
  3. ↑ 3.0 3.1 3.2 Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD (1996). "Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene". Nat. Genet. 14 (2): 141–5. doi:10.1038/ng1096-141. PMID 8841182.
  4. ↑ 4.0 4.1 Gorry MC, Gabbaizedeh D, Furey W, Gates LK, Preston RA, Aston CE, Zhang Y, Ulrich C, Ehrlich GD, Whitcomb DC (1997). "Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis". Gastroenterology. 113 (4): 1063–8. PMID 9322498.
  5. ↑ Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P, Truninger K, Ammann R, Cavallini G, Charnley RM, Uomo G, Delhaye M, Spicak J, Drumm B, Jansen J, Mountford R, Whitcomb DC, Neoptolemos JP (2004). "Clinical and genetic characteristics of hereditary pancreatitis in Europe". Clin. Gastroenterol. Hepatol. 2 (3): 252–61. PMID 15017610.
  6. ↑ LaFemina J, Roberts PA, Hung YP, Gusella JF, Sahani D, Fernández-del Castillo C, Warshaw AL, Thayer SP (2009). "Identification of a novel kindred with familial pancreatitis and pancreatic cancer". Pancreatology. 9 (3): 273–9. doi:10.1159/000201553. PMC 3713708. PMID 19407482.
  7. ↑ LaRusch J, Barmada MM, Solomon S, Whitcomb DC (2012). "Whole exome sequencing identifies multiple, complex etiologies in an idiopathic hereditary pancreatitis kindred". JOP. 13 (3): 258–62. PMC 3651649. PMID 22572128.
  8. ↑ Schneider A, Larusch J, Sun X, Aloe A, Lamb J, Hawes R, Cotton P, Brand RE, Anderson MA, Money ME, Banks PA, Lewis MD, Baillie J, Sherman S, Disario J, Burton FR, Gardner TB, Amann ST, Gelrud A, George R, Rockacy MJ, Kassabian S, Martinson J, Slivka A, Yadav D, Oruc N, Barmada MM, Frizzell R, Whitcomb DC (2011). "Combined bicarbonate conductance-impairing variants in CFTR and SPINK1 variants are associated with chronic pancreatitis in patients without cystic fibrosis". Gastroenterology. 140 (1): 162–71. doi:10.1053/j.gastro.2010.10.045. PMC 3171690. PMID 20977904.
  9. ↑ Rosendahl J, Landt O, Bernadova J, Kovacs P, Teich N, Bödeker H, Keim V, Ruffert C, Mössner J, Kage A, Stumvoll M, Groneberg D, Krüger R, Luck W, Treiber M, Becker M, Witt H (2013). "CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated?". Gut. 62 (4): 582–92. doi:10.1136/gutjnl-2011-300645. PMID 22427236.
  10. ↑ Teich N, Mössner J, Keim V (1998). "Mutations of the cationic trypsinogen in hereditary pancreatitis". Hum. Mutat. 12 (1): 39–43. doi:10.1002/(SICI)1098-1004(1998)12:1<39::AID-HUMU6>3.0.CO;2-P. PMID 9633818.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Hereditary_pancreatitis_pathophysiology&oldid=1430178"