title: Two newborn-onset patients of Upshaw-Schulman syndrome with distinct subsequent clinical courses.
abstract: Upshaw-Schulman syndrome (USS) is caused by a congenital deficit in ADAMTS13 activity owing to genetic mutations. USS is characterized by severe neonatal jaundice with a negative Coombs test and repeated childhood episodes of thrombocytopenia reversible by fresh frozen plasma (FFP) infusions. We present two patients with USS, both of whom underwent exchange blood transfusions as newborns, although the disease subsequently developed along different clinical courses. USS-CC5 initially received a diagnosis of neonatal jaundice due to fetomaternal ABO incompatibility with an indirect positive Coombs test, which masked the diagnosis of USS. Before prophylactic FFP infusions were initiated, USS-CC5 had chronic thrombocytopenia. In contrast, thrombocytopenia developed in USS-HH4 only in response to infections and spontaneously normalized without FFP infusions. Analyses of the ADAMTS13 genes in USS-CC5 and USS-HH4 revealed compound heterozygotes of p.R398C/p.Q723K and p.Q449X/p.Q1374Sfs, respectively. Analysis of von Willebrand factor (VWF) multimers in plasma samples taken from both patients in remission showed single symmetrical multimer bands, which differ from the triplet structure of bands observed in normal samples. These data suggested that plasma VWF multimers in the patients had not been proteolytically modified. Our results indicate the presence of a previously unknown regulatory mechanism for VWF-dependent high-shear stress-induced platelet aggregation.
authors.affiliation: Department of Pediatrics, Nihonkai General Hospital, Sakata, Yamagata, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Tanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kimura
authors.forename: Ayami
authors.initials: A
authors.lastname: Isonishi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kato
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Masaki
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ohtaki
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D051722:ADAM Proteins / Q000097:blood / Q000235:genetics*; D000071120:ADAMTS13 Protein; D001704:Biopolymers; D001787:Blood Group Incompatibility / Q000175:diagnosis; D003298:Coombs Test; D004252:DNA Mutational Analysis; D003951:Diagnostic Errors; D005078:Exchange Transfusion, Whole Blood; D005260:Female; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D007239:Infections / Q000097:blood; D007567:Jaundice, Neonatal / Q000175:diagnosis / Q000628:therapy; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010949:Plasma; D010974:Platelet Aggregation; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D014841:von Willebrand Factor / Q000737:chemistry*
chemical_list: D000017:ABO Blood-Group System; D001704:Biopolymers; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human