Document Detail

von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP.
MedLine Citation:
PMID:  12393505     Owner:  NLM     Status:  MEDLINE    
Thrombotic thrombocytopenic purpura (TTP) is caused by the persistence of the highly reactive high-molecular-weight multimers of von Willebrand factor (VWF) due to deficiency of the specific VWF-cleaving protease (VWF-CP) ADAMTS13, resulting in microangiopathic disease. The acquired form is caused by autoantibodies against VWF-CP, whereas homozygous or compound heterozygous mutations of ADAMTS13 are responsible for recessively inherited TTP. We investigated 83 children with hemolytic or thrombocytopenic episodes with or without additional neurologic symptoms or renal failure. The presumed diagnosis was chronic idiopathic thrombocytopenic purpura (ITP; n = 50), TTP (n = 8), hemolytic uremic syndrome (HUS; n = 24), and Evans syndrome (n = 1). A severe deficiency of VWF-CP (< or = 5%) was found in all investigated patients with TTP and in none of those with HUS. Additionally, 2 of 50 patients with a prior diagnosis of ITP were deficient for VWF-CP. Antibodies against VWF-CP were found in 4 children. Mutation analysis of the ADAMTS13 gene in the patients deficient in VWF-CP by direct sequencing of all 29 exons identified 8 different mutations, suggesting the hereditary form of TTP in 1 patient with ITP, in the patient with Evans syndrome, and in 5 of the 8 patients with TTP. The phenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, oligosymptomatic forms may occur that can delay the identification of patients at risk.
Reinhard Schneppenheim; Ulrich Budde; Florian Oyen; Dorothea Angerhaus; Volker Aumann; Elke Drewke; Wolf Hassenpflug; Johannes Häberle; Karim Kentouche; Elisabeth Kohne; Karin Kurnik; Dirk Mueller-Wiefel; Tobias Obser; René Santer; Karl-Walter Sykora
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Publication Detail:
Type:  Journal Article     Date:  2002-10-17
Journal Detail:
Title:  Blood     Volume:  101     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-13     Completed Date:  2003-04-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1845-50     Citation Subset:  AIM; IM    
Children's University Hospital, Hamburg-Eppendorf; Lab Association Prof Arndt and Partners, Coagulation Laboratory, Hamburg, Germany.
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MeSH Terms
ADAM Proteins
Amino Acid Substitution
Antibody Specificity
Autoantibodies / blood,  immunology
Autoimmune Diseases / diagnosis,  enzymology,  genetics,  immunology
Child, Preschool
Codon, Nonsense
DNA Mutational Analysis*
Diagnosis, Differential
Diagnostic Errors
Genetic Heterogeneity
Hemolytic-Uremic Syndrome / diagnosis,  enzymology,  genetics
Metalloendopeptidases / deficiency,  genetics*,  immunology
Mutation, Missense
Point Mutation
Protein Structure, Tertiary
Purpura, Thrombocytopenic, Idiopathic / diagnosis,  enzymology
Purpura, Thrombotic Thrombocytopenic / congenital,  diagnosis,  enzymology,  genetics*
Reg. No./Substance:
0/Autoantibodies; 0/Codon, Nonsense; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/ADAMTS13 protein, human; EC 3.4.24.-/Metalloendopeptidases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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