The Role of Kidney Biopsy in Fabry Disease

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency and subsequent accumulation of glycosphingolipids, including globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), in multiple organs. This acc...

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Main Authors: Irene Capelli, Laura Martano, Gian Marco Berti, Gisella Vischini, Sarah Lerario, Vincenzo Donadio, Alex Incensi, Valeria Aiello, Francesca Ciurli, Benedetta Fabbrizio, Stefano Chilotti, Renzo Mignani, Gianandrea Pasquinelli, Gaetano La Manna
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Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/4/767
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author Irene Capelli
Laura Martano
Gian Marco Berti
Gisella Vischini
Sarah Lerario
Vincenzo Donadio
Alex Incensi
Valeria Aiello
Francesca Ciurli
Benedetta Fabbrizio
Stefano Chilotti
Renzo Mignani
Gianandrea Pasquinelli
Gaetano La Manna
author_facet Irene Capelli
Laura Martano
Gian Marco Berti
Gisella Vischini
Sarah Lerario
Vincenzo Donadio
Alex Incensi
Valeria Aiello
Francesca Ciurli
Benedetta Fabbrizio
Stefano Chilotti
Renzo Mignani
Gianandrea Pasquinelli
Gaetano La Manna
author_sort Irene Capelli
collection DOAJ
description Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency and subsequent accumulation of glycosphingolipids, including globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), in multiple organs. This accumulation can result in multisystemic disease and life-threatening complications. FD presents with a broad phenotypic spectrum, ranging from the classic form, with early and severe symptoms, to a later-onset form with variable manifestations. The severity of the disease in females is more variable due to X-chromosome inactivation (XCI). Renal involvement is a key feature, and kidney biopsy remains a valuable tool for diagnosing FD and assessing the extent of nephropathy. Although molecular genetic testing is the gold standard for diagnosis, kidney biopsy aids in confirming renal involvement, detecting coexisting conditions, and determining the pathogenicity of variants of uncertain significance (VUSs). Moreover, kidney biopsy can serve as a prognostic tool by identifying early markers of nephropathy, such as foot process effacement and glomerular sclerosis, which predict disease progression. Emerging technologies, including machine learning, offer the potential to enhance the analysis of renal histology, improving diagnostic accuracy and patient stratification. Despite the challenges posed by overlapping diseases and potential misdiagnoses, kidney biopsy remains an essential component of FD diagnosis and management, facilitating early detection, the monitoring of disease progression, and the evaluation of therapeutic responses.
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spelling doaj-art-af4a52e3e7824da59eecfd9627c5fe7f2025-08-20T03:14:17ZengMDPI AGBiomedicines2227-90592025-03-0113476710.3390/biomedicines13040767The Role of Kidney Biopsy in Fabry DiseaseIrene Capelli0Laura Martano1Gian Marco Berti2Gisella Vischini3Sarah Lerario4Vincenzo Donadio5Alex Incensi6Valeria Aiello7Francesca Ciurli8Benedetta Fabbrizio9Stefano Chilotti10Renzo Mignani11Gianandrea Pasquinelli12Gaetano La Manna13Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, ItalyNephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyNephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyNeuromuscular and Neuroimmunology Unit, Bellaria Hospital, IRCCS Institute of Neurological Sciences of Bologna, 40139 Bologna, ItalyNeuromuscular and Neuroimmunology Unit, Bellaria Hospital, IRCCS Institute of Neurological Sciences of Bologna, 40139 Bologna, ItalyNephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyNephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyPathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyPathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyNephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDepartment of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna, 40126 Bologna, ItalyNephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyFabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to α-galactosidase A deficiency and subsequent accumulation of glycosphingolipids, including globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3), in multiple organs. This accumulation can result in multisystemic disease and life-threatening complications. FD presents with a broad phenotypic spectrum, ranging from the classic form, with early and severe symptoms, to a later-onset form with variable manifestations. The severity of the disease in females is more variable due to X-chromosome inactivation (XCI). Renal involvement is a key feature, and kidney biopsy remains a valuable tool for diagnosing FD and assessing the extent of nephropathy. Although molecular genetic testing is the gold standard for diagnosis, kidney biopsy aids in confirming renal involvement, detecting coexisting conditions, and determining the pathogenicity of variants of uncertain significance (VUSs). Moreover, kidney biopsy can serve as a prognostic tool by identifying early markers of nephropathy, such as foot process effacement and glomerular sclerosis, which predict disease progression. Emerging technologies, including machine learning, offer the potential to enhance the analysis of renal histology, improving diagnostic accuracy and patient stratification. Despite the challenges posed by overlapping diseases and potential misdiagnoses, kidney biopsy remains an essential component of FD diagnosis and management, facilitating early detection, the monitoring of disease progression, and the evaluation of therapeutic responses.https://www.mdpi.com/2227-9059/13/4/767biopsyhistopathologyFabry nephropathypodocyteinclusions
spellingShingle Irene Capelli
Laura Martano
Gian Marco Berti
Gisella Vischini
Sarah Lerario
Vincenzo Donadio
Alex Incensi
Valeria Aiello
Francesca Ciurli
Benedetta Fabbrizio
Stefano Chilotti
Renzo Mignani
Gianandrea Pasquinelli
Gaetano La Manna
The Role of Kidney Biopsy in Fabry Disease
Biomedicines
biopsy
histopathology
Fabry nephropathy
podocyte
inclusions
title The Role of Kidney Biopsy in Fabry Disease
title_full The Role of Kidney Biopsy in Fabry Disease
title_fullStr The Role of Kidney Biopsy in Fabry Disease
title_full_unstemmed The Role of Kidney Biopsy in Fabry Disease
title_short The Role of Kidney Biopsy in Fabry Disease
title_sort role of kidney biopsy in fabry disease
topic biopsy
histopathology
Fabry nephropathy
podocyte
inclusions
url https://www.mdpi.com/2227-9059/13/4/767
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