P PURI1,2, K KARPE1, G WALTERS1,3, S JIANG1,3
1The Canberra Hospital Renal Department, Canberra, Australia, 2The Westmead Hospital Renal department, Westmead, Australia, 3Centre for Personalised Immunology, NHMRC Centre for Research Excellence, Australia; Australian National University, Canberra ACT 2601, Australia
Introduction: Atypical haemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) characterised by abnormal alternate complement pathway activation that can arise as a result of mutations in complement regulatory proteins. This case illustrates how mutations in this pathway may led to multisystem a disorder.
Case discussion: A 50-year-old lady of Bangladeshi descent with a history Lupus, presented with TMA and thrombocytopaenia. Investigations revealed marked schistocytes on blood film, undetectable haptoglobins, increased LDH but negative DCT. She underwent several unsuccessful plasma exchanges until her normal ADAMTS-13 activity result became available, excluding TTP. She was then treated with steroids, and Rituximab for potential Lupus flare, however there was limited response. Due to ongoing haemolysis and kidney injury a diagnosis of aHUS was made and Eculizumab therapy commenced. During her admission she developed new onset cardiomyopathy left ventricular failure. This was thought to be related to her aHUS. Whole exome sequencing identified a homozygous novel missense mutation in CFHR3 (Ch1:196748315 A/G) which is a putative genetic cause for her presentation. Peripheral flow cytometry during and after her Eculizumab treatment displayed a reduction in naïve CD4+Tcells, increased CD4+T-effector memory cells and T regulatory cells compared to healthy controls (HC). The expansion plasma blast and anergic B cells suggested her immunophenotype displayed a significant antibody response. After 12 months treatment with Eculizumab, her aHUS appeared controlled and serial echocardiograms showed resolution of her cardiomyopathy.
Conclusion: This case highlights a novel CFHR3 mutation that may confer risk in developing aHUS and aHUS related cardiomyopathy. This case however, remains hypothesis generating with a consideration for familial genetic screening for the patient’s offspring.
Final year Nephrology AT.