title: Experiences in a family with the Upshaw-Schulman syndrome over a 44-year period.
abstract: A family with a novel c.717_del frameshift and a c.3655C > T missense mutation of a disintegrin and metalloproteinase with thrombospondin type I motif, member 13 protein (ADAMTS13) is described. Family members have been under observation for 44 years. Two double heterozygotes have severe early-onset Upshaw-Schulman syndrome and require prophylactic plasma infusions. Analysis reveals that 2 weekly plasma infusions are not sufficient in preventing laboratory evidence of a thrombotic thrombocytopenic purpura (TTP) attack. Both the double heterozygotes also have a heterozygous factor V Leiden G1291A mutation. One underwent splenectomy, which did not reduce the frequency of TTP episodes but resulted in a recurrent pulmonary embolism and has necessitated lifelong anticoagulant therapy. The other has mild chronic renal failure and has had episodes of atrial fibrillation and cerebral infarction. Of the 3 heterozygotes in the family, 1 has had episodes of mild thrombocytopenia.
authors.affiliation: 1Department of Haematology, The Emek Medical Centre, Afula, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Bennett
authors.forename: Yevgeni
authors.initials: Y
authors.lastname: Chubar
authors.forename: Israel
authors.initials: I
authors.lastname: Gavish
authors.forename: Ariel
authors.initials: A
authors.lastname: Aviv
authors.forename: Galia
authors.initials: G
authors.lastname: Stemer
authors.forename: Dafna
authors.initials: D
authors.lastname: Chap-Marshak
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000235:genetics; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D055815:Young Adult
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: Upshaw-Schulman syndrome; congenital; purpura; splenectomy; therapy; thrombotic thrombocytopenic; thrombotic thrombocytopenic purpura