Abstrato

Life-threatening atypical haemolytic uremic syndrome and cardiomyopathy related to novel CFHR3 mutation in a patient with lupus.

Prianka Puri, Lavinia Petrescu, Matthew Cook, MitaliFadia, Krishna Karpe, Simon Jiang

A 50-year-old Bangladeshi female with a background of Lupus, presented with biopsy proven thrombotic microangiopathy. She underwent empiric plasma exchange with limited efficacy, subsequently her ADAMTS-13 activity retuned to be normal excluding thrombotic thrombocytopenic purpura. She was then treated with prednisolone, and Rituximab for a possible Lupus flare, with minimal response. Due to ongoing haemolysis and progressive kidney injury a diagnosis of atypical haemolytic uremic syndrome (aHUS) was made and Eculizumab therapy commenced. During her admission she developed new onset non-ischemic cardiomyopathy. It was thought her cardiomyopathy was related to her aHUS, and she underwent immunophenotyping and whole exome. This identified a novel homozygous missense mutation in CFHR3 (Ch1:196748315 A/G). Peripheral flow cytometry displayed an expansion in plasma blast and anergic B cells suggesting her immunophenotype displayed a significant antibody response. After 12-months of Eculizumab treatment it was noted her haematological parameters normalized, and a subsequent echocardiogram showed resolution of her heart dysfunction, coinciding with the resolution of her aHUS.

Conclusion: This case highlights a novel CFHR3 mutation that may confer risk for developing aHUS and related cardiomyopathy. There is future consideration for familial genetic screening for the patient?s offspring, given disease severity.