Abstract: TH-PO191

Incidental Finding of CFHR5 Mutation in a Case of Hemolytic Uremic Syndrome

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Shapiro, Matthew H, LSUHSC Pediatrics, New Orleans, Louisiana, United States
  • Aviles, Diego H., LSUHSC Pediatrics, New Orleans, Louisiana, United States
  • Ashoor, Isa, LSUHSC Pediatrics, New Orleans, Louisiana, United States
Background

Hemolytic-uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency. It’s divided into two categories, diarrhea-positive (D+HUS) or typical HUS and diarrhea-negative or atypical HUS (aHUS).

Methods

A previously healthy 7 year old boy presented with several days of abdominal pain, emesis and bloody diarrhea. Admission labs were notable for Hgb 13.7 gm/dL, Platelets 485k/mm3 and creatinine 0.5 mg/dL. Stool culture, C. diff and Shiga toxin assays were negative. He subsequently developed oliguria and acute kidney injury. Urine was positive for blood (+3), protein (+3) and granular casts. Hgb and platelets fell to 7.1 gm/dL and 22K/mm3, respectively. Creatinine peaked at 4 mg/dL at which point hemodialysis was started. aHUS was suspected and additional labs were drawn. Complement C3/C4 and ADAMST13 levels were normal. Genetic testing for 11 genes implicated in thrombotic microangiopathy identified a mutation of unknown significance in the intron of Complement Factor H Related Protein 5 (CFHR5) gene. Renal function returned to baseline within a week without complement inhibition therapy and remains normal 3 months later.

Conclusion

We present a case of likely D+HUS where we were unable to isolate shiga toxin. This is further complicated by the incidental finding of a mutation in a complement regulating gene of unknown significance in aHUS, that has other known associations with disease. CFHR5 is associated with protection of glomerular cells against complement activation, yet mutations in the CFHR5 gene do not necessarily cause HUS, as they are also present in control populations. CFHR5 exon mutations have been described in association with various nephropathies, particularly in Cypriot patients, but few mention HUS, and none have described an intron mutation or its relationship to HUS. Importantly, CFHR5 mutations described in aHUS patients are in coding regions, not the in intron. This CFHR5 intron mutation is not predicted to alter or affect splicing, therefore it is unlikely to play a role in this particular case. Hence, complement inhibition with eculizumab is perhaps not indicated. Long-term monitoring is warranted.