Abstract: PUB187
Nephrotic Syndrome in the Setting of Phospholipase A2 Receptor (PLA2R)-Positive Membranous Nephropathy with Coexisting NUP93 Mutation, ADPKD Type 1, and HBB Mutation
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Borissov, Martin, University of Maryland Medical System, Baltimore, Maryland, United States
- Onder, Songul, University of Maryland Baltimore School of Medicine, Baltimore, Maryland, United States
- Ismail, Abdel-Latif, University of Maryland Medical System, Baltimore, Maryland, United States
Group or Team Name
- University of Maryland Midtown Campus.
Introduction
This case highlights a diagnostically and genetically complex presentation of nephrotic syndrome characterized by the coexistence of PLA2R-positive membranous nephropathy at the setting of a heterozygous truncated ADPKD Type 1 variant, and multiple genetic variants, including a likely pathogenic NUP93 mutation and a heterozygous HBB mutation.
Case Description
She was presented at age 30 with PKD and edema. Her PLA2R antibody was positive. Due to polycystic kidney morphology, renal biopsy was deferred. Laboratory findings supported nephrotic syndrome, [proteinuria (3.9 g/24h), hypoalbuminemia (1.7 g/dL)], and serum creatinine 0.69 mg/dL. She was treated with tacrolimus and furosemide, which improved edema and led to PLA2R antibody negativity. However, nonadherence to therapy led to persistent non-nephrotic range proteinuria. She was later lost to follow-up and returned at age 33, at which time genetic testing was performed due to the absence of a family history of ADPKD.
Discussion
Genetic analysis revealed a likely pathogenic NUP93 mutation, a heterozygous truncated ADPKD Type 1 variant, and a heterozygous HBB mutation. PLA2R-positive membranous nephropathy remains the most likely cause of nephrotic syndrome, supported by serologic findings and treatment response. However, the NUP93 mutation, commonly linked to monogenic steroid-resistant nephrotic syndrome in children, may represent an incidental factor. The HBB mutation is unrelated to nephrotic syndrome but is relevant in the context of sickle cell trait.
This case emphasizes integrating serologic, imaging, and genetic data in evaluating complex renal presentations.