Congenital Thrombotic Thrombocytopenic Purpura With a Novel ADAMTS13 Gene Mutation.

ABSTRACT

Congenital thrombotic thrombocytopenic purpura (TTP) is an autosomal recessive disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and thrombosis. Congenital TTP should also be considered while investigating neonatal hyperbilirubinemia, hemolytic anemia, or isolated thrombocytopenia. This case is of an 8-year-old male child who presented with prolonged and recurrent history of thrombocytopenia and MAHA, first identified when he was seven weeks of age preceding neonatal hyperbilirubinemia. Peripheral blood smear examination showed thrombocytopenia and schistocytes. He then went through a series of laboratory investigations until at the age of seven years, when the ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) antigen level was performed and found to be low 40 ng/ml (630-850). Subsequently, he received a trial of steroids and rituximab which were found to be ineffective and associated with complications. In this case, a definitive diagnosis was delayed until the age of eight years when a novel homozygous pathogenic frameshift variant ADAMTS13 c.3033delC, p.Cys1012AlafsX109 in exon 23 was identified. After receiving regular plasma infusions, thrombocytopenia and hemolysis improved. Congenital TTP should be considered in every neonatal hyperbilirubinemia, thrombocytopenia or hemolytic anemia to avoid delay in diagnosis. Early diagnosis through analysis of the ADAMTS13 gene is crucial for optimal management as well as for genetic counselling.