Abstract: FR-PO443
Recurrent Hemolysis in a Child With Shiga Toxin-Producing Escherichia coli and Two Heterozygous Variants Associated With Atypical Hemolytic Uremic Syndrome
Session Information
- Pediatric Nephrology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1102 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Chati, Priyanka, Inova Fairfax Hospital, Falls Church, Virginia, United States
- Mohtat, Davoud, Inova Fairfax Hospital, Falls Church, Virginia, United States
- Seo-Mayer, Patricia, Inova Fairfax Hospital, Falls Church, Virginia, United States
Introduction
The most common cause of hemolytic uremic syndrome in children is shiga toxin-producing E. coli (STEC-HUS). We report a patient with STEC-HUS who had an unusually persistent course, leading to discovery of two heterozygous gene variants associated with atypical HUS (aHUS).
Case Description
A 4 year old girl presented with vomiting and bloody stools. Stool PCR was positive for shiga toxin and labs showed hemolytic anemia, thrombocytopenia, hematuria, proteinuria, hypertension and AKI. The diagnosis was STEC-HUS. She received supportive care and required one red blood cell transfusion. Diarrhea and thrombocytopenia resolved and creatinine nadired at 0.6mg/L. One month post-discharge, she acquired a viral illness and developed worsened anemia, increased LDH and recurrence of thrombocytopenia, resulting in readmission.
Due to persistence of HUS, additional workup was pursued, including C3 (81mg/dL, ref 82-163mg/dL) and genetic testing for aHUS. Due to suspicion for aHUS, eculizumab treatment was initiated. Ultimately two heterozygous mutations were identified: a known pathogenic variant in Complement Factor I (CFI): (c.123 A>T), and a mutation in Complement Factor H (CFH) (c.2918 G>A), a variant of unknown significance. One parent carries the CFI mutation; the other has the CFH mutation. Both are well without any history of HUS. After 9 months, eculizumab treatment was paused and the patient has not had recurrence of HUS (Figure 1).
Discussion
This case illustrates the role of genetic testing in selected cases of STEC-HUS and the efficacy of eculizumab in an unusual combination of CFI/CFH variants causing aHUS. This combination has never been previously reported. Eculizumab was effective in halting hemolysis in our patient, but she has done well without chronic treatment.
Figure 1: Laboratory trends in relation to discharge from 1st hospitalization, onset of viral illness prior to 2nd hospitalization, Eculizumab (Ecu) initiation and final dose of Ecu.