Kidney Week

Abstract: SA-PO0149

Collapsing FSGS in a Child with Fabry Disease: Causality or Coincidence?

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

• Gueiros, Ana Paula, Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE, Brazil

Ana Paula Gueiros, MD, PhD

• Dantas, Gustavo Coelho, Hospital Santa Joana, Recife, PE, Brazil

Gustavo Coelho Dantas, MD

• Araujo, Stanley A., Instituto de Nefropatologia, Belo Horizonnte, MG, Brazil

Stanley A. Araujo, MD, MBBS

• Wanderley, David Campos, Instituto de Nefropatologia, Belo Horizonnte, MG, Brazil

David Campos Wanderley

• Siqueira, Ana Cecília Menezes, Instituto de Medicina Integral Professor Fernando Figueira, Recife, PE, Brazil

Ana Cecília Menezes Siqueira, MD

Introduction

Fabry disease (FD) is caused by mutations in the GLA gene, resulting in reduced or absent activity of α-galactosidase A and accumulation of globotriaosylceramide and its metabolites (Lyso Gb3). Fabry nephropathy is characterized by podocyte injury, glomerulosclerosis, interstitial fibrosis, and vascular involvement. No association between collapsing focal segmental glomerulosclerosis (FSGS) and FD has ever been reported. We describe a child with collapsing FSGS whose exome analysis revealed a GLA mutation.

Case Description

An 11-year-old girl was admitted with uremic syndrome after an influenza-like illness, with no prior medical or family history of renal disease. However, six months earlier, serum creatinine was 2.2 mg/dL and proteinuria 3.5 g/day. Dialysis (HD) was initiated and kidney biopsy performed. Light microscopy: 18/37 globally sclerosed glomeruli, and 11 with capillary collapse, synechiae and marked podocyte hyperplasia, consistent with collapsing FSGS. Tubulointerstitial fibrosis and tubular atrophy were moderate; arteries were mildly thickened. Semi-thin sections showed extensive (>90%) podocyte vacuolization with complete foot process effacement. Immunofluorescence: negative. Electron microscopy: epithelial cell attenuation, microvillous transformation, and extensive foot process effacement, with no accumulation of metabolites or zebra bodies. In preparation for kidney transplantation, exome sequencing identified a pathogenic c.593T>C mutation in GLA, and the APOL1 G1 allele (G1/G0). The patient was asymptomatic for FD; brain and cardiac MRI and audiometry were normal. Ophthalmologic evaluation showed anterior lens opacities in both eyes, with reduced visual acuity; Lyso Gb3 was 0.2 ng/mL. Her mother was found to carry the same mutation and had bilateral cataract surgery at 42 years, without comorbidities. Now aged 13, the patient remains on HD and has not started FD treatment.

Discussion

Given the patient's pediatric age, female, and late-onset mutation, we believe that collapsing FSGS is unlikely to represent a manifestation of FD. However, the presence of bilateral cataracts—a relatively uncommon feature in FD—suggests that, in this family, the c.593T>C mutation may exhibit an atypical phenotype. The heterogeneity of FD warrants further clinical investigation of this family in order to provide evidence of the mutation's pathogenicity and to enable early treatment.