Congenital thrombotic thrombocytopenic purpura due to a novel homozygous mutation in the ADAMTS13 gene: a case report

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening form of thrombotic microangiopathy (TMA) characterized by recurrent episodes of thrombocytopenia and microangiopathic hemolytic anemia (MAHA), sometimes associated with ischemic damage of the brain and kidneys. Congenital TTP (cTTP), also known as Upshaw–Schulman syndrome, is a rare disease caused by compound heterozygous, or more rarely, homozygous mutations in the gene encoding the von Willebrand factor (VWF) cleaving protease, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). The disease course in cTTP is variable and genotype-phenotype correlations are complex. In this report we describe a case of cTTP in a patient from Saudi Arabia caused by a novel homozygous mutation (c.2882delC; p.Cys962Alafs*3) predicted to result in truncation of a third of the C-terminal region of the ADAMTS13 protein, including the distal TSP-1 and CUB domains. The cTTP in our patient was characterized by severe ADAMTS13 deficiency (<2%), early onset (severe neonatal hyperbilirubinemia) recurrent episodes of thrombocytopenia and MAHA, requiring prophylactic treatment with fresh frozen plasma infusions. No neurological or renal manifestations were present. This case report provides further evidence that both the distal TSP-1 and CUB domains are essential for the VWF-cleaving activity of ADAMTS13.