Abstract: FR-PO0930
Pathogenic Variant-Negative Atypical Hemolytic Uremic Syndrome in a Three-Month-Old Infant: Diagnostic Challenges and Dilemmas in Eculizumab Withdrawal
Session Information
- Pediatric Nephrology: Genetic Diseases, Development, Neonatal Nephrology, Glomerular Diseases, and More
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Eisenberg, Sarah Leah, Tulane University School of Medicine, New Orleans, Louisiana, United States
- Krieger, Adam, Tulane University School of Medicine, New Orleans, Louisiana, United States
- Khorki, Mohamad Eyad, Tulane University School of Medicine, New Orleans, Louisiana, United States
Introduction
Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) driven by alternative complement pathway dysregulation. Distinguishing infection-triggered secondary TMA from primary genetic aHUS in infancy remains difficult, especially in mutation-negative cases where optimal complement inhibition duration is uncertain.
Case Description
A 3-month-old female with failure to thrive and hypertonia presented with hypercapnic respiratory failure from human metapneumovirus and bacterial pneumonia. She progressed to multiorgan failure, pancytopenia, and oliguric acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). ADAMTS13 activity was 43.2%, excluding thrombotic thrombocytopenic purpura. Complement assays revealed alternative pathway activation (sC5b-9 351 ng/mL, Bb 6.60 μg/mL, CH50 29 U/mL), confirming aHUS. After three plasma exchange sessions, eculizumab was initiated. Rapid whole-genome sequencing identified compound heterozygous POLR3A variants of uncertain significance. Aside from one report linking 4H leukodystrophy to aHUS, workup showed no pathogenic mutations. Renal function recovered, CRRT was discontinued, and she was discharged on maintenance eculizumab.
Three months later, extended-interval dosing trials were complicated by worsening hypertension, mild lactate dehydrogenase (LDH) elevation, declining serum albumin, and downtrending CH50 suggesting subclinical complement reactivation. Standard dosing frequency was resumed.
Discussion
This case highlights the dilemma of infection-triggered versus unrecognized genetic aHUS in mutation-negative infants. At 3 months, primary genetic aHUS is more likely than secondary TMA, narrowing equipoise around eculizumab withdrawal. Current data indicates that 30-50% of aHUS cases lack identifiable complement mutations or anti-complement factor H autoantibodies. Relapse risk after eculizumab discontinuation is 20-30% overall, but lower in mutation-negative patients than in those with identified pathogenic variants. Further, relapses may cause irreversible injury before therapy can be resumed. Subtle signs of relapse, including hypertension and LDH or albumin changes, are nonspecific post-AKI sequelae that complicate decision-making. Validated biomarkers and evidence-based withdrawal protocols for infantile mutation-negative aHUS are needed.