Association of Atypical Hemolytic Uremic Syndrome With Wilms' Tumor 1 Gene Mutations: A Case Series and Literature...

Atypical hemolytic uremic syndrome (aHUS) is a life‑threatening condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, as well as acute kidney injury (AKI). It can occur primarily due to complement gene mutations or secondary to another underlying condition. Several cases with Wilms' tumor gene 1 (WT1) mutations that presented with aHUS have been reported. Here, we report four cases of children diagnosed with WT1 mutations and presented initially with aHUS. There are two boys and two girls who presented with thrombotic microangiopathy (TMA), high lactate dehydrogenase, fragmented red blood cell (RBCs), and severe hypertension. All of them were anuric from the first presentation. Therapy with C5 inhibitors was initiated immediately and was associated with hematological remission without renal recovery. Renal replacement therapy (RRT) was started for all of the patients. A renal biopsy was conducted on two patients and showed global glomerulosclerosis. A genetic study identified pathogenic mutations in the WT1 gene. Two of the patients became dialysis dependent, and two patients underwent renal transplantation without the recurrence of aHUS. Our case series emphasizes that a diagnosis of WT1 mutation can be considered in children with aHUS with severe renal manifestations without a response to C5 inhibitors and with global glomerulosclerosis on renal biopsy. To our knowledge, this is the first report of a series of cases of WT1 mutations in pediatric patients presenting with clinical manifestation manifestations of aHUS. This unique finding highlights an association between HUS and WT1 mutation.