Atypical Hemolytic Uremic Syndrome During Induction Chemotherapy in Neuroblastoma, a Rare Phenomenon or Common Congenital Predisposition?

Atypical hemolytic uremic syndrome (aHUS) is an infrequently encountered complement-mediated thrombotic microangiopathy (TMA) usually associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) with severe hypertension arise due to aberrant complement protein activation in the circulation and significant endothelial damage. Transplant-associated thrombotic microangiopathy has been increasingly recognized after high dose carboplatin, etoposide, and melphalan-chemotherapy followed by autologous hematopoietic stem cell rescue for treatment of children with neuroblastoma (NB). We report the case of a 13-month-old boy with metastatic neuroblastoma who developed aHUS during the first cycle of induction chemotherapy. Germline testing revealed a Complement factor H (CFH) gene mutation, Cys357Arg, which is currently classified as a variant of uncertain significance (VUS), although likely pathogenic based on molecular modeling as well as this patient’s clinical presentation. The patient has been successfully managed with complement blockade therapy with no recurrence of disease. We review presentations of neuroblastoma with hypertension, along with AKI and thrombocytopenia, to raise awareness about the potential for aHUS in patients with newly diagnosed NB.