Adult-Onset Hereditary Thrombotic Thrombocytopenic Purpura Presenting as Kidney Failure: A Heterozygous ADAMTS13...

Hereditary thrombotic thrombocytopenic purpura (TTP) is a rare autosomal recessive disorder caused by ADAMTS13 deficiency, typically presenting in childhood or early adulthood. We describe an atypical presentation of hereditary TTP in a 55-year-old man presenting with acute kidney injury on a background of diabetic kidney disease, without prior suggestive history or identifiable triggers. Initial evaluation revealed features of thrombotic microangiopathy, including haemolysis, thrombocytopenia, with preserved coagulation parameters. Presumptive complement-mediated thrombotic microangiopathy was treated with eculizumab; however, the patient progressed to dialysis dependence and developed transient neurological symptoms. ADAMTS13 activity was reduced (8 U/dL) without a detectable inhibitor, prompting treatment with fresh frozen plasma (FFP), which resulted in haematologic and neurological improvement. Kidney biopsy demonstrated acute thrombotic microangiopathy superimposed on advanced diabetic and vascular disease. Genetic testing identified a heterozygous pathogenic ADAMTS13 variant (c.587C>T; p.Thr196Ile) without a second pathogenic allele. Additional long-read sequencing detected polymorphisms that may be associated with reduced ADAMTS13 activity, however current evidence suggests that these are variants of unknown significance (VUS). Although these variants have been associated with variation in ADAMTS13 levels in population or functional studies, the contribution of the additional variants remains uncertain. Functional response to FFP with transient correction of ADAMTS13 levels supported a diagnosis of hereditary TTP. The patient was commenced on regular FFP infusions and has been stable without further haematological or neurological events. He remains dialysis-dependent, awaiting kidney transplantation. This case highlights a late-onset, atypical presentation of hereditary TTP and raises important questions regarding the pathogenicity of heterozygous variants and modifying polymorphisms. It underscores the need to consider ADAMTS13 deficiency in unexplained thrombotic microangiopathy and kidney failure, even in the absence of classic features or biallelic mutations.