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West et al. Rare Dis Orphan Drugs J 2024;3:22 Rare Disease and
DOI: 10.20517/rdodj.2023.61
Orphan Drugs Journal

Review Open Access

Fabry nephropathy: a treatable cause of chronic
kidney disease

2
Michael L. West 1 , Laurette Geldenhuys , Daniel G. Bichet 3
1
Division of Nephrology, Department of Medicine, Dalhousie University, Halifax, NS B3H 1V7, Canada.
2
Division of Anatomical Pathology, Department of Pathology, QE II Health Sciences Centre, Halifax, NS B3H 1V8, Canada.
3
Division of Nephrology, Department of Medicine, University of Montreal, Montreal, QC H4J 1C5, Canada.
Correspondence to: Dr. Michael L. West, Division of Nephrology, Department of Medicine, Dalhousie University, B06 CCR, QE II
Health Sciences Centre, 5790 University Ave, Halifax, NS B3H 1V7, Canada. E-mail: mlwest@dal.ca

How to cite this article: West ML, Geldenhuys L, Bichet DG. Fabry nephropathy: a treatable cause of chronic kidney disease. Rare
Dis Orphan Drugs J 2024;3:22. https://dx.doi.org/10.20517/rdodj.2023.61

Received: 25 Dec 2023 First Decision: 7 Mar 2024 Revised: 8 Apr 2024 Accepted: 25 Jun 2024 Published: 11 Jul 2024
Academic Editor: Daniel Scherman Copy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
Fabry disease is a rare X-linked inborn error of metabolism that has a high prevalence of chronic kidney disease
(CKD) and renal failure. It is due to the deficiency of the α-galactosidase A (α-Gal) lysosomal enzyme with
subsequent accumulation of globotriaosylceramide (Gb3) in lysosomes. In the kidney, the podocyte is the main
target of this disease, although all cell types are involved. The podocyte, being terminally differentiated, does not
replicate and thus accumulates Gb3 throughout life. Podocytes are injured by Gb3, leading to their detachment
from the glomerular basement membrane and subsequent loss in the urine. Albuminuria starts in childhood and
progresses to overt proteinuria in the teens and 20 s. CKD ensues with adults starting dialysis at an average age of
42 years. Patients have a high prevalence of stroke and cardiomyopathy with hypertrophic change, heart failure,
and dysrhythmias. Patient survival is limited in both genders. Diagnosis is based on the demonstration of a low
α-Gal activity and a pathogenic GLA mutation. Clinical features are highly variable, which makes recognition of this
condition difficult. Treatment with intravenous recombinant human enzyme replacement therapy (ERT) and oral
pharmacologic chaperone are available. Control of proteinuria to 0.5 g/day or less is of critical importance to limit
progression to end-stage renal disease. Early initiation of treatment gives the best results, but the optimal age to
start is uncertain. Fabry nephropathy remains a challenge due to its multisystem nature, difficult diagnosis, and
complicated management. It is important as a treatable cause of CKD.

Keywords: Rare disease, enzyme replacement therapy, pharmacologic chaperone, Fabry disease, Gb3, lyso-Gb3

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
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