FABRY DISEASE: CASE REPORT AND LITERATURE REVIEW
DOI:
https://doi.org/10.56238/levv16n53-095Keywords:
Fabry Disease, Proteinuria, Chronic Kidney Disease, Enzyme Replacement Therapy, MigalastatAbstract
Fabry disease is a rare X-linked disorder caused by α-galactosidase A (α-GAL) deficiency, leading to accumulation of glycosphingolipids (Gb3/Lyso-Gb3) and multisystemic manifestations, particularly renal, cardiac, and neurological. We report the case of a 44-year-old man with significant proteinuria and rapid progression to end-stage chronic kidney disease requiring hemodialysis, initially attributed to nonsteroidal anti-inflammatory drug use, later diagnosed as Fabry disease. This case highlights the phenotypic heterogeneity and the risk of underdiagnosis in nephropathies of uncertain etiology. The literature review emphasizes renal involvement as a key prognostic determinant, related to podocyte injury induced by Gb3/Lyso-Gb3 and by inflammatory/fibrogenic pathways. Diagnosis should integrate clinical evaluation, enzyme activity measurement, genetic testing, and, in selected scenarios, renal biopsy. Enzyme replacement therapy remains the mainstay of treatment, while migalastat represents an alternative for amenable variants. Emerging strategies—substrate reduction therapy, pegunigalsidase-α, and gene therapy—expand the therapeutic landscape. Prognosis depends on phenotype, sex, and timing of diagnosis, with early intervention associated with better outcomes. In conclusion, Fabry disease should be considered in the differential diagnosis of nephropathies with significant proteinuria and rapid progression, and timely initiation of disease-specific therapy and nephroprotective measures is essential.
Downloads
References
1. Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5:30. DOI: https://doi.org/10.1186/1750-1172-5-30
2. Ortiz A, Germain DP, Desnick RJ, et al. Fabry disease revisited: Management and treatment recommendations for adult patients. Mol Genet Metab. 2018;123(4):416-427. DOI: https://doi.org/10.1016/j.ymgme.2018.02.014
3. Spada M, Pagliardini S, Yasuda M, et al. High incidence of later-onset Fabry disease revealed by newborn screening. Am J Hum Genet. 2006;79(1):31-40. DOI: https://doi.org/10.1086/504601
4. Germain DP, Hughes DA, Nicholls K, et al. Treatment of Fabry’s disease with the pharmacologic chaperone migalastat. N Engl J Med. 2016;375(6):545-555. DOI: https://doi.org/10.1056/NEJMoa1510198
5. Aerts JM, Groener JE, Kuiper S, et al. Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proc Natl Acad Sci USA. 2008;105(8):2812-2817. DOI: https://doi.org/10.1073/pnas.0712309105
6. Hughes DA, Nicholls K, Shankar SP, et al. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet. 2017;54(4):288-296. DOI: https://doi.org/10.1136/jmedgenet-2016-104178
7. Bokhari SRA, Zulfiqar H, Hariz A. Fabry Disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; [atualizado 2023 Jul 4; citado 2025 Aug 22]. Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK435996/
8. Chan B, Adam DN. A review of Fabry disease. Skin Therapy Lett. 2018;23(2):4–6.
9. Dinu IR, Popa CC, Anca IA. Fabry disease—current data and therapeutic approaches. J Med Life. 2021;14(4):449–454.
10. Angelini C, Bar C, Baudier MP, Fergelot P, Lancelot G, Rooryck C, et al. Prevalence of Fabry disease in patients with chronic pain: lessons from the DOUFAB and DOUFABIS studies. Eur J Pain. 2025;29(1):e4708. doi:10.1002/ejp.4708. DOI: https://doi.org/10.1002/ejp.4708
11. Ying Q, et al. Late-onset Fabry disease presenting with unexplained renal failure, left ventricular hypertrophy, and recurrent syncope: a case report. Orphanet J Rare Dis. 2025; doi:10.1186/s13023-025-03791-4. DOI: https://doi.org/10.1186/s13023-025-03791-4
12. Schiffmann R, Fuller M, Clarke LA, Aerts JMFG. Is it Fabry disease? Genet Med. 2016;18(12):1181–1185. DOI: https://doi.org/10.1038/gim.2016.55
13. Arends M, Wanner C, Hughes D, Mehta A, Oder D, Watkinson OT, et al. Characterization of classical and nonclassical Fabry disease: a multicenter study. J Am Soc Nephrol. 2017;28(5):1631–1641. DOI: https://doi.org/10.1681/ASN.2016090964
14. Moiseev S, Fomin V, Savostyanov K, Mukhin N, Sholomova I, Pushkov A, et al. Prevalence and clinical features of Fabry disease in hemodialysis patients: Russian nationwide Fabry dialysis screening program. Clin Kidney J. 2019;12(4):576–582. DOI: https://doi.org/10.1159/000495886
15. Abensur H, Reis MA. Acometimento renal na doença de Fabry. J Bras Nefrol. 2016;38(2):245–254. DOI: https://doi.org/10.5935/0101-2800.20160034
16. Kok K, Garzuly F, Shytaj IL, et al. Fabry Disease: Molecular Basis, Pathophysiology, Diagnosis and Potential Therapeutic Directions. Biomolecules. 2021;11(2):271. DOI: https://doi.org/10.3390/biom11020271
17. Dutra-Clarke M, Tapia D, Curtin E, Rünger D, Lee GK, Lakatos A, et al. Variable clinical features of patients with Fabry disease and outcome of enzyme replacement therapy. Mol Genet Metab Rep. 2021;26:100700. DOI: https://doi.org/10.1016/j.ymgmr.2020.100700
18. Jovanovic A, Miller-Hodges E, Castriota F, Evuarherhe O, Ayodele O, Hughes D, et al. Clinical efficacy and real-world effectiveness of Fabry disease treatments: a systematic literature review. J Clin Med. 2025;14(14):5131. DOI: https://doi.org/10.3390/jcm14145131
19. Jaurretche SPA, Antongiovanni N, Perretta F. Direct correlation between age at diagnosis and severity of nephropathy in Fabry disease patients. Indian J Nephrol. 2019;29(6):398–401. DOI: https://doi.org/10.4103/ijn.IJN_167_18
20. Monte Neto JT, Kirsztajn GM. The role of podocyte injury in the pathogenesis of Fabry disease nephropathy. Braz J Nephrol. 2024;46(3):e20240035. doi:10.1590/2175-8239-JBN-2024-0035en. DOI: https://doi.org/10.1590/2175-8239-jbn-2024-0035pt
21. Zhang D, Xie K, Zhang J. Fabry nephropathy: focus on podocyte damage and therapeutic target. J Transl Genet Genom. 2024;8:302-11. doi:10.20517/jtgg.2024.39. DOI: https://doi.org/10.20517/jtgg.2024.39
22. Capelli I, Martano L, Berti GM, Vischini G, Lerario S, Donadio V, et al. The role of kidney biopsy in Fabry disease. Biomedicines. 2025;13(4):767. doi:10.3390/biomedicines13040767. DOI: https://doi.org/10.3390/biomedicines13040767
23. Silva CAB, Moura-Neto JA, Reis MA, Vieira Neto OM, Barreto FC. Renal manifestations of Fabry disease: a narrative review. Can J Kidney Health Dis. 2021;8:1-14. doi:10.1177/2054358120985627. DOI: https://doi.org/10.1177/2054358120985627
