Difficulties in diagnosing congenital thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura is a very rare condition, especially its familial, genetically determined type called Upshaw Schulman Syndrome (OMIM musical sharp274150). The study presents 2 families of patients in which congenital thrombotic thrombocytopenic purpura were diagnosed. Symptoms of the disease, such as thrombocytopenia, microangiopathic hemolytic anemia, and kidney disorders were pronounced with varying degrees of severity in 5 children of various ages from these families. Before the final diagnosis, patients were treated for idiopathic thrombocytopenia, hemolytic anemia, and hemolytic-uremic syndrome, respectively. The study was focused on finding the factors responsible for hemolytic anemia. The activity of a disintegrin and metalloprotease with thrombospondin type 1 motif, 13 (ADAMTS13) and ADAMTS13 antibodies were evaluated and genetic tests were performed. Severe ADAMTS13 deficiency was detected in all affected siblings. The diagnosis of Upshaw Schulman Syndrome was confirmed by molecular testing of the gene encoding the von Willebrand factor cleaving protease ADAMTS13 which revealed compound heterozygosity for 1045C>T (R349C) and 3107C>A (S1036X) in the patients of family 1 and homozygosity for the common mutation 4143insA in the patients of family 2. Regular fresh-frozen plasma transfusions were sufficient to control the disease.