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Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS 13 gene
Author(s) -
Rank Cecilie Utke,
Kremer Hovinga Johanna,
Taleghani Magnus Mansouri,
Lämmle Bernhard,
Gøtze Jens Peter,
Nielsen Ove Juul
Publication year - 2014
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/ejh.12197
Subject(s) - adamts , thrombotic thrombocytopenic purpura , missense mutation , thrombotic microangiopathy , compound heterozygosity , medicine , adamts13 , von willebrand factor , thrombospondin , platelet , immunology , mutation , metalloproteinase , biology , gene , genetics , matrix metalloproteinase , disease
Upshaw– S chulman syndrome ( USS ) is due to severe congenital deficiency of von W illebrand factor ( VWF )‐cleaving protease ADAMTS 13 (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 ADAMTS 13 activity of <1% of normal plasma without the presence of inhibitors of ADAMTS 13. ADAMTS 13 deficiency was caused by two new mutations of the ADAMTS 13 gene: a deletion of a single nucleotide in exon17 (c. 2042 delA) leading to a frameshift ( K 681 C fs X 16), and a missense mutation in exon 25 (c.3368 G > A ) leading to p.R1123H. This case report confirms the importance of the analysis of the ADAMTS 13 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.