Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
REVIEWS   (Open Access)

Advances in Diagnosis and Treatment of Fabry Disease: A Review of Clinical Manifestations and Therapeutic Interventions

Mikhail A. Popov 1, Anastasia V. Poznyak 2*, Vladislav V. Dontsov 1, Julia Y. Kotalevskaya 1, Alexey B. Zulkarnaev 1, Vadim S. Tsyplakov 1, Margarita A. Sazonova 3, Marina D. Sazonova 3, Elizaveta M. Pleshko 4, Dmitry F. Beloyartsev 5, Alexander L. Golovyuk 5, Alexey V. Churov 6, Dmitriy Yu. Serdyukov 7, Arthur A. Lee 4, 8, Victor Y Glanz 4, Vasily N. Sukhorukov 4, and Alexander N. Orekhov 4*

+ Author Affiliations

Journal of Angiotherapy 8(3) 1-10 https://doi.org/10.25163/angiotherapy.839505

Submitted: 31 January 2024  Revised: 09 March 2024  Published: 12 March 2024 

This review discussed a treatment algorithm for advancing medicine, and patient outcomes of Fabry disease.

Abstract


At present, early diagnosis of many orphan diseases is difficult due to their rare occurrence and insufficient knowledge of them. This article presents a review of the literature and our study of Fabry disease (FD), a rare genetic multisystem disease which belongs to the group of lysosomal storage diseases. This disease is based on a deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A), which leads to the progressive accumulation of glycolipid Gb3 in lysosomes in almost all cells of the body, causing extensive organ damage and an increase in plasma levels of globotriaosylsphingosine (lyso-Gb3 product of degradation of accumulated Gb3. Objective: The aim is to provide a comprehensive overview of modern knowledge and current research in the field of pathophysiology, diagnosis and treatment of heart damage in FD, to evaluate the characteristics of diagnosed patients living on the territory of the Moscow region, and to develop and propose for spreading an algorithm for the early detection of this pathology. Methods: A retrospective analysis of the medical records of 12 patients with an estab-lished diagnosis of Fabry disease was carried out. Data from 12 patients with FD, undergoing enzyme replacement therapy of varying durations were analyzed. All patients had left ventricular hypertrophy (LVH) and hypertrophic cardiomyopathy, with 9 having LVH diagnosed during a diagnosis. 7 patients get a cardioprotective therapy. All patients underwent molecular genetic testing. In 3 cases there was fa-tal case. Results: The data were analyzed and molecular genetic markers of FD were detected for the purpose of selective screening for FD in the study sample. Conclusion: An algorithm for the early diagnosis of FD has been developed and presented for distribution among general practitioners and cardiologists.

Keywords: Orphan diseases, Fabry disease, Agalsidase alfa, Fabry disease detection algorithm

References


Arends, M., Wanner, C., Hughes, D., Mehta, A., Oder, D., Watkinson, O. T., Elliott, P. M., Linthorst, G. E., Wijburg, F. A., Biegstraaten, M., & Hollak, C. E. (2017). Characterization of Classical and Nonclassical Fabry Disease: A Multicenter Study. Journal of the American Society of Nephrology : JASN, 28(5), 1631–1641. https://doi.org/10.1681/ASN.2016090964

Azevedo, O., Gago, M. F., Miltenberger-Miltenyi, G., Robles, A. R., Costa, M. A., Pereira, O., Vide, A. T., Castelo Branco, G., Simões, S., Guimarães, M. J., Salgado, A., Sousa, N., & Cunha, D. (2020). Natural history of the late-onset phenotype of Fabry disease due to the p.F113L mutation. Molecular genetics and metabolism reports, 22, 100565. https://doi.org/10.1016/j.ymgmr.2020.100565

Azevedo, O., Gago, M. F., Miltenberger-Miltenyi, G., Robles, A. R., Costa, M. A., Pereira, O., Vide, A. T., Castelo Branco, G., Simões, S., Guimarães, M. J., Salgado, A., Sousa, N., & Cunha, D. (2020). Natural history of the late-onset phenotype of Fabry disease due to the p.F113L mutation. Molecular genetics and metabolism reports, 22, 100565. https://doi.org/10.1016/j.ymgmr.2020.100565

Azevedo, O., Gago, M. F., Miltenberger-Miltenyi, G., Sousa, N., & Cunha, D. (2020). Fabry Disease Therapy: State-of-the-Art and Current Challenges. International journal of molecular sciences, 22(1), 206. https://doi.org/10.3390/ijms22010206

Azevedo, O., Gal, A., Faria, R., Gaspar, P., Miltenberger-Miltenyi, G., Gago, M. F., Dias, F., Martins, A., Rodrigues, J., Reimão, P., Pereira, O., Simões, S., Lopes, E., Guimarães, M. J., Sousa, N., & Cunha, D. (2020). Founder effect of Fabry disease due to p.F113L mutation: Clini-cal profile of a late-onset phenotype. Molecular genetics and metabolism, 129(2), 150–160. https://doi.org/10.1016/j.ymgme.2019.07.012

Azevedo, O., Gal, A., Faria, R., Gaspar, P., Miltenberger-Miltenyi, G., Gago, M. F., Dias, F., Martins, A., Rodrigues, J., Reimão, P., Pereira, O., Simões, S., Lopes, E., Guimarães, M. J., Sousa, N., & Cunha, D. (2020). Founder effect of Fabry disease due to p.F113L mutation: Clini-cal profile of a late-onset phenotype. Molecular genetics and metabolism, 129(2), 150–160. https://doi.org/10.1016/j.ymgme.2019.07.012

Beck, M., Ramaswami, U., Hernberg-Ståhl, E., Hughes, D. A., Kampmann, C., Mehta, A. B., Nicholls, K., Niu, D. M., Pintos-Morell, G., Reisin, R., West, M. L., Schenk, J., Anagnostopoulou, C., Botha, J., & Giugliani, R. (2022). Twenty years of the Fabry Outcome Survey (FOS): insights, achievements, and lessons learned from a global patient registry. Orphanet journal of rare diseases, 17(1), 238. https://doi.org/10.1186/s13023-022-02392-9

Bernardes, T. P., Foresto, R. D., & Kirsztajn, G. M. (2020). Fabry disease: genetics, pathology, and treatment. Revista da Associacao Medica Brasileira (1992), 66Suppl 1(Suppl 1), s10–s16. https://doi.org/10.1590/1806-9282.66.S1.10

Branton, M. H., Schiffmann, R., Sabnis, S. G., Murray, G. J., Quirk, J. M., Altarescu, G., Goldfarb, L., Brady, R. O., Balow, J. E., Austin Iii, H. A., & Kopp, J. B. (2002). Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clini-cal course. Medicine, 81(2), 122–138. https://doi.org/10.1097/00005792-200203000-00003

Chimenti, C., Russo, M. A., & Frustaci, A. (2010). Atrial biopsy evidence of Fabry disease causing lone atrial fibrillation. Heart (British Cardiac Society), 96(21), 1782–1783. https://doi.org/10.1136/hrt.2010.196162

Cybulla, M., Nicholls, K., Feriozzi, S., Linhart, A., Torras, J., Vujkovac, B., Botha, J., Anagnostopoulou, C., West, M. L., & FOS Study Group (2022). Renoprotective Effect of Agalsidase Alfa: A Long-Term Follow-Up of Patients with Fabry Disease. Journal of clinical medicine, 11(16), 4810. https://doi.org/10.3390/jcm11164810

Desnick, R. J., Astrin, K. H., & Bishop, D. F. (1989). Fabry disease: molecular genetics of the inherited nephropathy. Advances in nephrol-ogy from the Necker Hospital, 18, 113–127.

Domm, J. M., Wootton, S. K., Medin, J. A., & West, M. L. (2021). Gene therapy for Fabry disease: Progress, challenges, and outlooks on gene-editing. Molecular genetics and metabolism, 134(1-2), 117–131. https://doi.org/10.1016/j.ymgme.2021.07.006

Duro, G., Zizzo, C., Cammarata, G., Burlina, A., Burlina, A., Polo, G., Scalia, S., Oliveri, R., Sciarrino, S., Francofonte, D., Alessandro, R., Pisani, A., Palladino, G., Napoletano, R., Tenuta, M., Masarone, D., Limongelli, G., Riccio, E., Frustaci, A., Chimenti, C., … Colomba, P. (2018). Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?. International journal of molecular sciences, 19(12), 3726. https://doi.org/10.3390/ijms19123726

Eng, C. M., Fletcher, J., Wilcox, W. R., Waldek, S., Scott, C. R., Sillence, D. O., Breunig, F., Charrow, J., Germain, D. P., Nicholls, K., & Banikazemi, M. (2007). Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry. Journal of inherited metabolic disease, 30(2), 184–192. https://doi.org/10.1007/s10545-007-0521-2

Engle, R. L., Mohr, D. C., Holmes, S. K., Seibert, M. N., Afable, M., Leyson, J., & Meterko, M. (2021). Evidence-based practice and pa-tient-centered care: Doing both well. Health care management review, 46(3), 174–184. https://doi.org/10.1097/HMR.0000000000000254

Fabry J: Ein Beitrag zur Kenntniss der Purpura haemorrhagicanodularis (Purpura papulosahaemorrhagicaHebrae) .Archf Dermat.1898,43:187-200. 10.1007/BF01986897

Germain, D. P., Charrow, J., Desnick, R. J., Guffon, N., Kempf, J., Lachmann, R. H., Lemay, R., Linthorst, G. E., Packman, S., Scott, C. R., Waldek, S., Warnock, D. G., Weinreb, N. J., & Wilcox, W. R. (2015). Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease. Journal of medical genetics, 52(5), 353–358. https://doi.org/10.1136/jmedgenet-2014-102797

Izhar, R., Borriello, M., La Russa, A., Di Paola, R., De, A., Capasso, G., Ingrosso, D., Perna, A. F., & Simeoni, M. (2023). Fabry Disease in Women: Genetic Basis, Available Biomarkers, and Clinical Manifestations. Genes, 15(1), 37. https://doi.org/10.3390/genes15010037

Kampmann, C., Linhart, A., Baehner, F., Palecek, T., Wiethoff, C. M., Miebach, E., Whybra, C., Gal, A., Bultas, J., & Beck, M. (2008). Onset and progression of the Anderson-Fabry disease related cardiomyopathy. International journal of cardiology, 130(3), 367–373. https://doi.org/10.1016/j.ijcard.2008.03.007

Kubota, T., Tsukimura, T., Shiga, T., Togawa, T., & Sakuraba, H. (2023). Monitoring of anti-drug antibodies and disease-specific bi-omarkers in three patients from a Japanese Fabry family treated with enzyme replacement therapy. CEN case reports, 12(2), 171–175. https://doi.org/10.1007/s13730-022-00738-7

Lenders, M., & Brand, E. (2021). Fabry Disease: The Current Treatment Landscape. Drugs, 81(6), 635–645. https://doi.org/10.1007/s40265-021-01486-1

Levstek, T., Vujkovac, B., & Trebusak Podkrajsek, K. (2020). Biomarkers of Fabry Nephropathy: Review and Future Perspective. Genes, 11(9), 1091. https://doi.org/10.3390/genes11091091

Li, X., Ren, X., Zhang, Y., Ding, L., Huo, M., & Li, Q. (2022). Fabry disease: Mechanism and therapeutics strategies. Frontiers in pharmacology, 13, 1025740. https://doi.org/10.3389/fphar.2022.1025740

Linhart, A., Kampmann, C., Zamorano, J. L., Sunder-Plassmann, G., Beck, M., Mehta, A., Elliott, P. M., & European FOS Investigators (2007). Cardiac manifestations of Anderson-Fabry disease: results from the international Fabry outcome survey. European heart journal, 28(10), 1228–1235. https://doi.org/10.1093/eurheartj/ehm153

Mehta, A., & Hughes, D. A. (2002). Fabry Disease. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.

Mehta, A., Beck, M., Elliott, P., Giugliani, R., Linhart, A., Sunder-Plassmann, G., Schiffmann, R., Barbey, F., Ries, M., Clarke, J. T., & Fabry Outcome Survey investigators (2009). Enzyme replacement therapy with agalsidase alfa in patients with Fabry's disease: an analysis of reg-istry data. Lancet (London, England), 374(9706), 1986–1996. https://doi.org/10.1016/S0140-6736(09)61493-8

Mehta, A., Beck, M., Linhart, A., Sunder-Plassmann, G., & Widmer, U. (2006). History of lysosomal storage diseases: an overview. In A. Mehta (Eds.) et. al., Fabry Disease: Perspectives from 5 Years of FOS. Oxford PharmaGenesis.

Mehta, A., Clarke, J. T., Giugliani, R., Elliott, P., Linhart, A., Beck, M., Sunder-Plassmann, G., & FOS Investigators (2009). Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey. Journal of medical genetics, 46(8), 548–552. https://doi.org/10.1136/jmg.2008.065904

Mehta, A., Ricci, R., Widmer, U., Dehout, F., Garcia de Lorenzo, A., Kampmann, C., Linhart, A., Sunder-Plassmann, G., Ries, M., & Beck, M. (2004). Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. European journal of clini-cal investigation, 34(3), 236–242. https://doi.org/10.1111/j.1365-2362.2004.01309.x

Meikle, P. J., Hopwood, J. J., Clague, A. E., & Carey, W. F. (1999). Prevalence of lysosomal storage disorders. JAMA, 281(3), 249–254. https://doi.org/10.1001/jama.281.3.249

Muntean, C., Starcea, I. M., Stoica, C., & Banescu, C. (2022). Clinical Characteristics, Renal Involvement, and Therapeutic Options of Pedi-atric Patients With Fabry Disease. Frontiers in pediatrics, 10, 908657. https://doi.org/10.3389/fped.2022.908657

Nakamura, K., Morita, H., Takaya, Y., Saito, Y., Miyoshi, T., Morinaga, H., Sugiyama, H., Wada, J., & Ito, H. (2023). Effects of Agalsidase Alfa Enzyme Replacement Therapy on Left Ventricular Hypertrophy on Electrocardiogram in a Female Patient with Fabry Disease. Inter-national heart journal, 64(3), 502–505. https://doi.org/10.1536/ihj.22-752

Oder, D., Nordbeck, P., & Wanner, C. (2016). Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease. Nephron, 134(1), 30–36. https://doi.org/10.1159/000448968

O'Mahony, C., Coats, C., Cardona, M., Garcia, A., Calcagnino, M., Murphy, E., Lachmann, R., Mehta, A., Hughes, D., & Elliott, P. M. (2011). Incidence and predictors of anti-bradycardia pacing in patients with Anderson-Fabry disease. Europace : European pacing, ar-rhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophys-iology of the European Society of Cardiology, 13(12), 1781–1788. https://doi.org/10.1093/europace/eur267

Palaiodimou, L., Kokotis, P., Zompola, C., Papagiannopoulou, G., Bakola, E., Papadopoulou, M., Zouvelou, V., Petras, D., Vlachopoulos, C., & Tsivgoulis, G. (2023). Fabry Disease: Current and Novel Therapeutic Strategies. A Narrative Review. Current neuropharmacology, 21(3), 440–456. https://doi.org/10.2174/1570159X20666220601124117

Patel, V., O'Mahony, C., Hughes, D., Rahman, M. S., Coats, C., Murphy, E., Lachmann, R., Mehta, A., & Elliott, P. M. (2015). Clinical and genetic predictors of major cardiac events in patients with Anderson-Fabry Disease. Heart (British Cardiac Society), 101(12), 961–966. https://doi.org/10.1136/heartjnl-2014-306782

Popli, S., Leehey, D. J., Molnar, Z. V., Nawab, Z. M., & Ing, T. S. (1990). Demonstration of Fabry's disease deposits in placenta. American journal of obstetrics and gynecology, 162(2), 464–465. https://doi.org/10.1016/0002-9378(90)90410-9

Puhl, A. C., & Ekins, S. (2022). Advancing the Research and Development of Enzyme Replacement Therapies for Lysosomal Storage Dis-eases. GEN biotechnology, 1(2), 156–162. https://doi.org/10.1089/genbio.2021.0013

Schwarting, A., Dehout, F., Feriozzi, S., Beck, M., Mehta, A., Sunder-Plassmann, G., & European FOS Investigators (2006). Enzyme re-placement therapy and renal function in 201 patients with Fabry disease. Clinical nephrology, 66(2), 77–84.

Shah, J. S., Hughes, D. A., Sachdev, B., Tome, M., Ward, D., Lee, P., Mehta, A. B., & Elliott, P. M. (2005). Prevalence and clinical significance of cardiac arrhythmia in Anderson-Fabry disease. The American journal of cardiology, 96(6), 842–846. https://doi.org/10.1016/j.amjcard.2005.05.033

Spada, M., Pagliardini, S., Yasuda, M., Tukel, T., Thiagarajan, G., Sakuraba, H., Ponzone, A., & Desnick, R. J. (2006). High incidence of lat-er-onset fabry disease revealed by newborn screening. American journal of human genetics, 79(1), 31–40. https://doi.org/10.1086/504601

Stroh E. (2011). Taking the family history in genetic disease: a guide for ophthalmologists. Current opinion in ophthalmology, 22(5), 340–346. https://doi.org/10.1097/ICU.0b013e3283496362

SWEELEY, C. C., & KLIONSKY, B. (1963). FABRY'S DISEASE: CLASSIFICATION AS A SPHINGOLIPIDOSIS AND PARTIAL CHARACTERIZATION OF A NOVEL GLYCOLIPID. The Journal of biological chemistry, 238, 3148–3150.

van der Tol, L., Smid, B. E., Poorthuis, B. J., Biegstraaten, M., Deprez, R. H., Linthorst, G. E., & Hollak, C. E. (2014). A systematic review on screening for Fabry disease: prevalence of individuals with genetic variants of unknown significance. Journal of medical genetics, 51(1), 1–9. https://doi.org/10.1136/jmedgenet-2013-101857

Vedder, A. C., Strijland, A., vd Bergh Weerman, M. A., Florquin, S., Aerts, J. M., & Hollak, C. E. (2006). Manifestations of Fabry disease in placental tissue. Journal of inherited metabolic disease, 29(1), 106–111. https://doi.org/10.1007/s10545-006-0196-0

Waldek, S., Patel, M. R., Banikazemi, M., Lemay, R., & Lee, P. (2009). Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry. Genetics in medicine : official journal of the American College of Medical Genetics, 11(11), 790–796. https://doi.org/10.1097/GIM.0b013e3181bb05bb

Weidemann, F., Jovanovic, A., Herrmann, K., & Vardarli, I. (2022). Chaperone Therapy in Fabry Disease. International journal of molecu-lar sciences, 23(3), 1887. https://doi.org/10.3390/ijms23031887

Weidemann, F., Niemann, M., Störk, S., Breunig, F., Beer, M., Sommer, C., Herrmann, S., Ertl, G., & Wanner, C. (2013). Long-term out-come of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications. Journal of internal medicine, 274(4), 331–341. https://doi.org/10.1111/joim.12077

Whybra, C., Kampmann, C., Willers, I., Davies, J., Winchester, B., Kriegsmann, J., Brühl, K., Gal, A., Bunge, S., & Beck, M. (2001). Ander-son-Fabry disease: clinical manifestations of disease in female heterozygotes. Journal of inherited metabolic disease, 24(7), 715–724. https://doi.org/10.1023/a:1012993305223

Full Text
Export Citation

View Dimensions


View Plumx



View Altmetric



0
Save
0
Citation
441
View
0
Share