Abstract: PUB612
Complement Factor I Gene Mutation with Normal Factor I Activity in a Child with ESRD Secondary to Atypical HUS
Session Information
Category: Trainee Case Reports
- 1600 Pediatric Nephrology
Authors
- Altemose, Kathleen Elizabeth, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- Moudgil, Asha, Children national Medical Center, Washington, District of Columbia, United States
- Atkinson, Meredith A., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
Introduction
Complement factor I (CFI) regulates the deleterious cytotoxic and inflammatory activity of the alternate complement pathway. CFI deficiency is a rare cause of atypical HUS (aHUS). We report a child diagnosed with ESRD secondary to aHUS who was found to have a CFI gene mutation with normal CFI activity.
Case Description
Our patient is a 10 yo boy with history of an encephalocele, seizures and hypertension who presented with hypertensive urgency and acute deterioration of renal function (serum creatinine 8.7 mg/dL) requiring CRRT. Following admission, his hemoglobin and platelets declined, requiring multiple blood product transfusions. Work-up for causes of acute on chronic renal failure were negative, including duplex US without renal artery stenosis, negative renal angiography, and negative serologies (ANA, anti-double stranded DNA and hepatitis panel). C3 was low at 64 mg/dl and C4 was normal on admission. Renal biopsy was significant for global glomerulosclerosis and tubular atrophy. HUS evaluation showed elevated LDH, normal haptoglobin, smear with schistocytes, and a normal ADAMTS13. Whole exome sequencing (GeneDx, OPKO Health) showed heterozygosity for a G119R variant classified as “likely pathogenic” in the CFI gene inherited from the paternal side. TMA complement panel (Cincinnati Children’s Hospital) revealed normal Factor H and B activity. Factor I activity was also normal at 3.2 mg/dl (reference range 2.4-4.9 mg/dl). The patient received a deceased donor renal transplant ~10 months after initial presentation. Due to genetic mutation in CFI, he has been treated with IV eculizumab at time of transplant and every 2 weeks since transplant. He had one episode of anemia requiring blood transfusion but has maintained his platelets in normal range with excellent allograft function (creatinine 0.5 mg/dl).
Discussion
In this patient with a known variant in the CFI gene and a history of ESRD, Factor I activity as measured on a TMA complement panel was within normal range. However, clinical presentation is consistent with aHUS, and he has remained stable on biweekly IV eculizumab infusions -post-transplant. This case supports the value of genetic investigation for causes of aHUS, even in the setting of normal factor H and/or I levels, in order to prevent disease recurrence after renal transplantation.