title: Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene.
abstract: Upshaw-Schulman syndrome (USS) is due to severe congenital deficiency of von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 domains, nr 13) activity resulting in the presence of unusually large forms of VWF in the circulation, causing intravascular platelet clumping and thrombotic microangiopathy. Our patient, a 26-year-old man, had attacks of thrombotic thrombocytopenic purpura (TTP) with thrombocytopenia and a urine dipstick positive for hemoglobin (4+), often as the only sign of hemolytic activity. He had ADAMTS13 activity of <1% of normal plasma without the presence of inhibitors of ADAMTS13. ADAMTS13 deficiency was caused by two new mutations of the ADAMTS13 gene: a deletion of a single nucleotide in exon17 (c. 2042 delA) leading to a frameshift (K681C fs X16), and a missense mutation in exon 25 (c.3368G>A) leading to p.R1123H. This case report confirms the importance of the analysis of the ADAMTS13 activity and its inhibitor in patients who have episodes of TTP, with a very low platelet count and sometimes without the classic biochemical signs of hemolysis.
authors.affiliation: Department of Hematology, Rigshospitalet University Hospital, Copenhagen, Denmark.
authors.forename: Cecilie Utke
authors.initials: CU
authors.lastname: Rank
authors.forename: Johanna
authors.initials: J
authors.lastname: Kremer Hovinga
authors.forename: Magnus Mansouri
authors.initials: MM
authors.lastname: Taleghani
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lämmle
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Gøtze
authors.forename: Ove Juul
authors.initials: OJ
authors.lastname: Nielsen
mesh_terms: D051722:ADAM Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000071120:ADAMTS13 Protein; D000328:Adult; D001323:Autoantibodies / Q000276:immunology; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13; Upshaw-Schulman syndrome; genetic disorder; thrombotic thrombocytopenic purpura; von Willebrand factor