Abstract: PUB192
Secondary FSGS of Unclear Etiology Unmasking COL4A3 Heterozygosity
Session Information
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases
Authors
- Mahfouz, Ratib Talal, Henry Ford Health System, Detroit, Michigan, United States
- Roche, Meaghan Sarah, Henry Ford Health System, Detroit, Michigan, United States
- Kumbar, Lalathaksha Murthy, Henry Ford Health System, Detroit, Michigan, United States
Introduction
Focal segmental glomerulosclerosis (FSGS) is a histologic lesion with diverse causes, including genetic mutations. While COL4A3 mutations are typically linked to Alport syndrome or thin basement membrane nephropathy, their role in adult-onset FSGS without family history is underrecognized.
Case Description
A 44-year-old Middle Eastern woman with normal BMI, history of gout, and longstanding hematuria and proteinuria since her 20s presented for evaluation of progressive kidney dysfunction. She denied NSAID use or family history of kidney disease. Vital signs were unremarkable. Labs showed creatinine 1.57 mg/dL, eGFR 41 mL/min/1.73 m2, UACR 718 mg/g, UPCR 0.84 g/g, and normal albumin (4.3 g/dL). Serologic workup including ANA, dsDNA, ANCA, anti-GBM, RF, SPEP, complement, hepatitis serologies, and HIV was negative. Urinalysis showed dysmorphic RBCs and RBC casts. Renal ultrasound revealed a right renal cyst without hydronephrosis or stones.
Kidney biopsy showed focal segmental glomerulosclerosis involving 3 of 9 glomeruli, with 5 globally sclerosed. No mesangial expansion, endocapillary hypercellularity, necrosis, or crescents were seen. Mild interstitial fibrosis and tubular atrophy (~20%), mild intimal arterial fibrosis, and arteriolar hyalinosis were present. Immunofluorescence showed trace mesangial staining for C3, IgA, IgM, and kappa/lambda light chains. No glomeruli were available for electron microscopy. Findings were consistent with secondary rather than primary FSGS. Given unclear etiology, genetic testing revealed two heterozygous COL4A3 variants. The patient denied hearing loss in herself or family. Her children were referred for genetic counseling.
Discussion
This case highlights the importance of considering genetic testing in adults with unexplained FSGS, especially in the absence of secondary triggers or family history. COL4A3 mutations can present atypically in adulthood without classic syndromic features. Early diagnosis can guide management and facilitate familial screening.
Segmental sclerosis with mild interstitial atrophy