Severe Hyperbilirubinemia in a Case of Non-transfusion Dependent Thalassemia (NTDT) with Coexisting Gilbert Syndrome and Congenital Thrombotic Thrombocytopenic Purpura (cTTP): A Rare Case Report

Abstract

Background: The coexistence of haemoglobinopathies and thrombotic microangiopathies is an exceedingly rare clinical occurrence, particularly when involving beta-thalassaemia intermedia, Gilbert syndrome, and congenital thrombotic thrombocytopenic purpura (cTTP). Each condition independently contributes to haemolysis and jaundice but their intersection represents a unique diagnostic and therapeutic challenge. Case Summary: We report a rare case of a young adult male with a long-standing history of recurrent jaundice since early childhood. Initially diagnosed with beta-thalassaemia minor and later confirmed to have coexisting Gilbert syndrome, the patient remained transfusion-independent until late adolescence. He subsequently developed severe and disproportionate hyperbilirubinemia with microangiopathic haemolytic features, thrombocytopenia, and evidence of iron overload. High-performance liquid chromatography (HPLC) and iron studies were consistent with beta-thalassaemia intermedia. Imaging revealed features of extramedullary haematopoiesis, intrahepatic cholestasis, splenic infarction, and splenic vein thrombosis. Notably, peripheral smear demonstrated schistocytes, raising the suspicion for thrombotic microangiopathy. Whole exome sequencing confirmed homozygous mutations in Hb Beta gene (beta-thalassaemia), UGT1A1 (Gilbert syndrome), and ADAMTS13 (cTTP), establishing a final diagnosis of a rare triple disorder. Liver biopsy revealed cholestatic liver injury with moderate fibrosis. Conclusion: This case underscores one of the rarest triads reported in hematology— beta-thalassemia intermedia, Gilbert syndrome, and congenital TTP. The overlapping clinical features demand a high index of suspicion and a comprehensive genetic evaluation when standard etiologies fail to explain persistent or severe hyperbilirubinemia. The report also highlights the importance of considering cTTP in patients with unexplained thrombocytopenia and hemolytic jaundice, even in the setting of known haemoglobinopathies. Early recognition is crucial for appropriate therapeutic intervention, long-term follow up and genetic counselling.