Clinical and genetic characteristics of pediatric hereditary thrombotic thrombocytopenic purpura: a case series of two novel ADAMTS13 variants and one previously reported variant

To characterize the clinical features, genetic mutations, and treatment strategies of hereditary thrombotic thrombocytopenic purpura (hTTP). Three pediatric hTTP cases were retrospectively analyzed for clinical manifestations, laboratory findings, ADAMTS13 activity, genetic results, family investigations, and treatment outcomes. All patients presented with recurrent thrombocytopenia with or without hemolytic anemia. ADAMTS13 activity was < 5% in Cases 2 and 3; in Case 1, activity was 13% when measured after treatment. ADAMTS13 inhibitors were negative in all three patients. Three ADAMTS13 variants were identified, including two previously unreported variants (c.1324 C > T, p.Gln442Ter and c.1459T > C, p.Cys487Arg) and one previously reported variant (c.1192 C > T, p.Arg398Cys). Case 1 carried compound heterozygous mutations (c.1324 C > T, p.Gln442Ter and c.1192 C > T, p.Arg398Cys), while Cases 2 and 3 carried homozygous mutations (c.1459T > C, p.Cys487Arg). hTTP is easily misdiagnosed because of its heterogeneous manifestations. Early recognition combined with ADAMTS13 activity testing and genetic analysis is essential for accurate diagnosis and timely treatment. Our study identified two previously unreported ADAMTS13 variants (c.1324 C > T, p.Gln442Ter and c.1459T > C, p.Cys487Arg) and one previously reported variant (c.1192 C > T, p.Arg398Cys) in pediatric patients with hTTP, providing additional clinical and genetic evidence for the molecular diagnosis of this rare disease. Recurrent thrombocytopenia, particularly in children with poor response to immune thrombocytopenia therapy, should prompt evaluation for hTTP.