Hereditary pancreatitis

Source: Wikipedia, the free encyclopedia.
Hereditary pancreatitis
This condition is inherited in an autosomal dominant manner

Hereditary pancreatitis (HP) is an

chromosome seven
(7q35).

The term "hereditary pancreatitis" is used when a genetic biomarker is identified, and "familial pancreatitis" otherwise.[3]

Presentation

HP is characterised by attacks of

exocrine failure and a mortally increased risk of pancreatic cancer. Lifetime risk of cancer has been variously calculated as 35–54%[4][5][6] to the age of 75 years and screening for early pancreatic cancer is being offered to HP sufferers on a scientific basis.[7] Some patients may choose to have their pancreas surgically removed to prevent pancreatic cancer from developing in the future.[8]

The epidemiology of HP follows a similar pattern to alcohol-associated chronic pancreatitis, but there are important differences. For example, HP typically has an earlier age of pancreatitis onset; although malabsorption and

diabetes mellitus occur at a later stage in the disease progression.[5]

Genetics

The vast majority of the cases of HP are caused by substitutions, at base 365 (c.365G>A) and base 86 of the cDNA (c.86A>T) on the

PRSS1 gene. The nucleotide substitutions were discovered in the late 1990s by classical linkage analysis[2][9]
and are now known as p.R122H and p.N29I respectively, according to the amino acid substitution and position in the protein sequence.

These mutations are rarely identified in general screens of patients with

idiopathic disease[10][11][12][13] and the phenotype of p.R122H and p.N29I is now well characterised[4][5][6] with the p.A16V mutation recently characterised for the first time.[14] There are many other rare mutations or polymorphisms of PRSS1 which remain less well understood[15][16]
and not all HP families have had the responsible genetic mutation identified.

The mechanism by which these genetic mutations cause pancreatitis is not yet known; but is likely to be the result of increased autoactivation[17] or reduced deactivation[18] of trypsinogen. However, a novel mechanism has recently been identified in a p.R116C kindred.[19]

Diagnosis

Families are defined as having HP,

first degree relatives (or three or more second degree relatives) to have unexplained recurrent-acute or chronic pancreatitis in two or more generations. It is an autosomal dominant disease with penetrance that is generally accepted to be ≈80%.[1][20]

Management

Treatment of HP resemble that of chronic pancreatitis of other causes. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction.(PMC1774562)[citation needed]

Prognosis

A 2009 study which followed 189 patients found no excess mortality despite the increased risk of pancreatic cancer.[21]

References

  1. ^
    PMID 14926813
    .
  2. ^
    S2CID 21974705
    .
  3. ISBN 978-0-19-538318-8
    . Retrieved 9 August 2011.
  4. ^
    PMID 9091646
    .
  5. ^
    PMID 15017610
    .
  6. ^
    S2CID 27464921
    .
  7. S2CID 29100310
    .
  8. PMID 23856911
    .
  9. PMID 9322498
    .
  10. S2CID 22717659
    .
  11. PMID 15329520
    .
  12. S2CID 21037146
    .
  13. PMID 10381903
    .
  14. S2CID 983450
    .
  15. PMID 16791840
    .
  16. PMID 20452997
    .
  17. PMID 16632094
    .
  18. S2CID 24473962
    .
  19. PMID 19191323
    .
  20. PMID 10446089
    .
  21. S2CID 2555617
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Hereditary_pancreatitis&oldid=1188143242"