[From gene to disease; congenital thrombotic thrombocytopenic purpura due to mutations in the ADAMTS13 gene]

Ned Tijdschr Geneeskd. 2003 Dec 6;147(49):2422-4.
[Article in Dutch]

Abstract

Thrombotic thrombocytopenic purpura (TTP) is characterised by haemolytic anaemia with fragmented erythrocytes and thrombocytopenia, accompanied by other symptoms such as renal dysfunction, neurological signs and fever. Proteolysis of the Von Willebrand blood-clotting factor (VWF) by a VWF cleaving protease or ADAMTS13 is decreased in patients with TTP, leading to ultra-large Von Willebrand multimers in the circulation. A lack of ADAMTS13 activity can be caused by autoimmune inhibitors or may be due to a constitutional deficiency of this protein. Recently, the ADAMTS13 gene that encodes for the ADAMTS13 protein was found. It was mapped to chromosome 9q34 and consists of 29 exons. Several mutations have been identified in the ADAMTS13 gene in patients with the congenital form of TTP. Symptomatic episodes in congenital TTP can be prevented by prophylactic plasma infusions every 2-3 weeks, hereby preventing further organ damage due to thrombotic microangiopathy.

Publication types

  • Review

MeSH terms

  • ADAM Proteins
  • ADAMTS13 Protein
  • Humans
  • Metalloendopeptidases / deficiency*
  • Metalloendopeptidases / genetics*
  • Metalloendopeptidases / metabolism
  • Mutation
  • Purpura, Thrombotic Thrombocytopenic / congenital
  • Purpura, Thrombotic Thrombocytopenic / enzymology
  • Purpura, Thrombotic Thrombocytopenic / genetics*
  • von Willebrand Factor / metabolism*

Substances

  • von Willebrand Factor
  • ADAM Proteins
  • Metalloendopeptidases
  • ADAMTS13 Protein
  • ADAMTS13 protein, human