Abstract: TH-PO216

Novel PLG Gene Mutation with Heterozygous CHFR1-R3 Deletion in a Patient with Atypical Hemolytic Uremic Syndrome and Lupus Nephritis

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Ali, Huzair, University of Oklahoma, Oklahoma City, Oklahoma, United States
  • Syed, Taseen Ahmed, University of Oklahoma Health Sciences Center, Oklahoma cty, Oklahoma, United States
  • Ghata, Joe, OUHSC, Oklahoma City, Oklahoma, United States
  • Abbas, Mubasher, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, United States
Background

Thrombotic Microangiopathy (TMA) is a disease characterized by intravascular thrombosis, hemolytic anemia, and endothelial cell damage, often contributing to renal failure. Atypical Hemolytic Uremic Syndrome (aHUS) is a complement mediated TMA. Most genetic abnormalities linked to aHUS relate to dysregulation of these complement and coagulation pathways. We describe a case of aHUS with lupus nephritis in a patient with a unique set of mutations, including the plasminogen (PLG) gene, recently linked to aHUS.

Methods

19 yo male presented with facial swelling, rash and fever for three days. On evaluation, he was in hypertensive emergency (>200/100mmHg), hypopigmented facial lesions with vitiligo on right ear. Labs demonstrated acute renal failure (Creatinine (Cr) 7.80mg/dL) requiring intermittent hemodialysis Work up revealed pancytopenia, ANA titer 1:320, positive schistocytes, low C3/C4 levels, normal ADAMTS13 activity, and negative infectious work up. Kidney biopsy showed diffuse proliferative glomerulonephritis consistent with Lupus nephritis (Class IV-A). Moreover, TMA affected the afferent arterioles. Renal Failure was refractory to PLEX, Steroids, Cellcept, and Rituximab. Renal Failure and hemolytic anemia only improved after Eculizumab, with Cr nadir to 2mg/dL upon discharge. Genetics later showed: (1) Heterozygous missense mutation of exon 2 & 10 of PLG gene, (2) Two polymorphisms in CFH gene, (3) Heterozygous polymorphism within an intron in MCP/CD46 (4) Heterozygous for the large CFHR1-CFHR3 deletion.

Conclusion

Mutations in the complement pathway have been described with atypical HUS. Coagulation pathway mutations are being linked with the pathogenesis of aHUS. Our patient developed renal TMA through complement dysregulation (via both classical & alternative pathways) likely through a double hit from Lupus nephritis flare, as well as underlying heterozygous genetic mutations (CHFR, CFH, & MCP/CD46 genes). In addition, dysregulation of the coagulation pathway through his PLG gene mutation likely contributed to his persistent renal TMA. This case suggests heterozygotes for these mutations may benefit from Eclizumab, especially in refractory cases of aHUS.