Abstract: SA-PO0143
De Novo Fabry Disease in a Female Patient Presenting with Nephrotic-Range Proteinuria
Session Information
- Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Oh, Jaha, Weill Cornell Medicine, New York, New York, United States
- Salvatore, Steven, Weill Cornell Medicine, New York, New York, United States
- Chevalier, James, Weill Cornell Medicine, New York, New York, United States
Introduction
Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient α-galactosidase A activity leading to globotriaosylceramide (GL3) accumulation in multiple renal cell types, particularly podocytes. Female patients often exhibit heterogeneous clinical manifestations, contributing to delayed diagnosis.
Case Description
A 44-year-old woman with recurrent optic neuritis, obesity, dyslipidemia, and chronic proteinuria presented with worsening proteinuria and new onset hypertension. She also reported decreased sweating and intermittent nocturnal tingling sensations. Urine protein-creatinine ratio was 4.5 g/day. Kidney biopsy demonstrated diffuse podocyte phospholipidosis with zebra bodies on electron microscopy (Figure 1), focal segmental and global glomerulosclerosis, and mild tubular atrophy/interstitial fibrosis. Genetic testing identified a heterozygous pathogenic GLA p.C172W mutation with reduced α-galactosidase A activity and elevated lyso-GL3 levels both in blood and urine, confirming Fabry disease. Family screening was negative, suggesting a de novo mutation. The patient was started on agalsidase beta enzyme replacement therapy with subsequent good disease control despite likely Fabry-associated cardiomyopathy on follow-up. Proteinuria improved with angiotensin receptor blocker and SGLT2 inhibitor therapy.
Discussion
This case highlights the diagnostic value of kidney biopsy and electron microscopy in female patients with unexplained proteinuria and multisystemic manifestations. The presence of zebra bodies and podocyte phospholipidosis prompted targeted genetic testing and early initiation of enzyme replacement therapy. This case further illustrates the phenotypic heterogeneity of Fabry disease in women and emphasizes the importance of early recognition before irreversible renal fibrosis and glomerulosclerosis develop.