Abstract: TH-PO506
Fabry Nephropathy: An Important Phenotype of the Mutation p.R356W (c.1066C>T)
Session Information
- Genetic Kidney Diseases: Genotypes and Phenotypes in Cases
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Albuquerque, Arquizia Morais, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil
- Siqueira, Ana Cecília Menezes, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil
- Gueiros, Ana Paula, Instituto de Medicina Integral Professor Fernando Figueira, Recife, Brazil
Introduction
Nephropathy is a serious manifestation of Fabry disease.
Kidney biopsy (KB) is a valuable tool for diagnosing nephropathy. The aim of
this study is to describe renal impairment in three generations of patients with
the p.R356W mutation.
Case Description
CASE 1- Male, aged 65, diabetes mellitus for 12 years. Enzyme activity (EA):
0.52 (VR >2.2 umol/L/h); Lyso-GB3: 1.8 (VR < 1.8 ng/mL); Creatinine (Cr) 1.6
mg/dL; proteinuria 2.2 g/24h. KB: Optical microscopy (OM): 4/9 glomeruli with
global sclerosis, foamy podocytes, mild tubular atrophy, and interstitial fibrosis,
moderate arteriolar hyalinosis, artery with moderate fibrointimal hyperplasia.
Electron microscopy (EM): lamellar inclusions in podocytes, thickened capillary
loops, podocyte foot process effacement.
CASE 2 Female, aged 50. EA: 2.2 (VR1.68-13.3 umol/L/h); Lyso-GB3: 1.6 (VR
< 2.0 ng/mL); Cr 0.6 mg/dL; proteinuria 0.2 g/24h; albuminuria 18.5 mg/L. KB
OM: segmental sclerosis in 3/47 glomeruli, global sclerosis in 2/47 glomeruli,
podocytes with large and vacuolated cytoplasm, interstitial fibrosis (<10%). EM:
podocytes with disorganized cytoplasm, foot process effacement containing
zebra bodies.
CASE 3 Male, aged 31. Lyso-GB3: 2.1 (VR < 0.8 ng/mL); Cr 0.76 mg/dL;
proteinuria 0.22 g/24h; urinary albumin/creatinine ratio (ACR) 9.15mg/g. KB:
diffuse podocyte vacuolation, preserved tubulointerstitium, arteries with slightly
thickened walls. EM: lamellar inclusions in podocytes, with foot process
effacement.
CASE 4 Female, aged 17. Cr 0.6 mg/dL; ACR 29 mg/g; Lyso-GB3: 0.8 (VR <
1.8 ng/mL). KB OM: Podocyte hypertrophy, artery with mild fibrointimal
hyperplasia, tubulointerstitium with no particularities. EM: podocytes with
voluminous cytoplasm containing inclusions with myelin figures and zebra
bodies and foot process effacement.
CASE 5 Male, aged 8. EA: 0.16 (VR 1.68-13.3 umol/L/h), Lyso-GB3: 6.5 (VR <
1.8 ng/mL); Cr 0.4 mg/dL; ACR 4.6 mg/g. KB OM: Discreet podocyte
hyperplasia, tubulointerstitial and vascular compartment with no particularities;
EM: focal lamellar inclusions in podocytes, endothelium, and tubules; preserved
foot process.
Discussion
This study demonstrates the importance of KB in an early
diagnosis of Fabry nephropathy and for understanding the phenotypic
presentation of the different mutations. This study has demonstrated the tropism
of the p.R356W mutation for the kidney.