C3 Glomerulonephritis in A20 Haploinsufficiency and TREX1 Mutation: A Case Report

The coexistence of pathogenic variants in multiple immune-regulating genes may result in complex and atypical clinical phenotypes. We present the case of a 9-year-old girl with a multisystem inflammatory disorder initially mimicking Systemic Lupus Erythematosus. Her renal biopsy revealed C3 glomerulonephritis, and subsequent investigation in her genome identified a pathogenic TNFAIP3 (A20 haploinsufficiency) variant together with a coexisting TREX1 variant. Treatment with corticosteroids, mycophenolate, and hydroxychloroquine led to a complete clinical and laboratory remission, including normalization of renal function and complement levels. This case highlights the importance of integrating renal pathology and genetic testing when systemic autoimmune presentations show atypical features.