Fabry disease revisited: Management and treatment recommendations for adult patients

Alberto Ortiz; Dominique P. Germain; Robert J. Desnick; Juan Politei; Michael Mauer; Alessandro Burlina; Christine Eng; Robert J. Hopkin; Dawn Laney; Aleš Linhart; Stephen Waldek; Eric Wallace; Frank Weidemann; William R. Wilcox

doi:10.1016/j.ymgme.2018.02.014

Fabry disease revisited: Management and treatment recommendations for adult patients

Alberto Ortiz, Dominique P. Germain, Robert J. Desnick, Juan Politei, Michael Mauer, Alessandro Burlina, Christine Eng, Robert J. Hopkin, Dawn Laney, Aleš Linhart, Stephen Waldek, Eric Wallace, Frank Weidemann, William R. Wilcox

Pediatric Nephrology

Research output: Contribution to journal › Review article › peer-review

489 Scopus citations

Abstract

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the “classic” phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. However, much of the current literature reports outcomes after late initiation of ERT, once substantial organ damage has already occurred. Updated monitoring and treatment guidelines for pediatric patients with Fabry disease have recently been published. Expert physician panels were convened to develop updated, specific guidelines for adult patients. Management of adult patients depends on 1) a personalized approach to care, reflecting the natural history of the specific disease phenotype; 2) comprehensive evaluation of disease involvement prior to ERT initiation; 3) early ERT initiation; 4) thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients; 5) use of adjuvant treatments for specific disease manifestations; and 6) management by an experienced multidisciplinary team.

Original language	English (US)
Pages (from-to)	416-427
Number of pages	12
Journal	Molecular Genetics and Metabolism
Volume	123
Issue number	4
DOIs	https://doi.org/10.1016/j.ymgme.2018.02.014
State	Published - Apr 2018

Bibliographical note

Funding Information:
The international panels of Fabry disease specialists (Atlanta, GA, USA, July 2014; Orlando, FL, USA, February 2015) were sponsored by Sanofi Genzyme. The authors received editorial/writing support in the preparation of this manuscript from Alessia Piazza, PhD, of Excerpta Medica, funded by Sanofi Genzyme, and from Hans Ebels of Sanofi Genzyme. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication. A.O. was supported by Intensificaci?n FIS and FEDER FundsREDINREN RD016/0019, and D.P.G. by the Plan National Maladies Rares of the French Ministry of Health.

Funding Information:
The international panels of Fabry disease specialists (Atlanta, GA, USA, July 2014; Orlando, FL, USA, February 2015) were sponsored by Sanofi Genzyme. The authors received editorial/writing support in the preparation of this manuscript from Alessia Piazza, PhD, of Excerpta Medica, funded by Sanofi Genzyme, and from Hans Ebels of Sanofi Genzyme. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication. A.O. was supported by Intensificación FIS and FEDER Funds REDINREN RD016/0019 , and D.P.G. by the Plan National Maladies Rares of the French Ministry of Health .

Publisher Copyright:
© 2018 The Authors

Keywords

Diagnosis
Fabry disease
Management
Mutation
Treatment

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10.1016/j.ymgme.2018.02.014

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Ortiz, A., Germain, D. P., Desnick, R. J., Politei, J., Mauer, M., Burlina, A., Eng, C., Hopkin, R. J., Laney, D., Linhart, A., Waldek, S., Wallace, E., Weidemann, F., & Wilcox, W. R. (2018). Fabry disease revisited: Management and treatment recommendations for adult patients. Molecular Genetics and Metabolism, 123(4), 416-427. https://doi.org/10.1016/j.ymgme.2018.02.014

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title = "Fabry disease revisited: Management and treatment recommendations for adult patients",

abstract = "Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the “classic” phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. However, much of the current literature reports outcomes after late initiation of ERT, once substantial organ damage has already occurred. Updated monitoring and treatment guidelines for pediatric patients with Fabry disease have recently been published. Expert physician panels were convened to develop updated, specific guidelines for adult patients. Management of adult patients depends on 1) a personalized approach to care, reflecting the natural history of the specific disease phenotype; 2) comprehensive evaluation of disease involvement prior to ERT initiation; 3) early ERT initiation; 4) thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients; 5) use of adjuvant treatments for specific disease manifestations; and 6) management by an experienced multidisciplinary team.",

keywords = "Diagnosis, Fabry disease, Management, Mutation, Treatment",

author = "Alberto Ortiz and Germain, {Dominique P.} and Desnick, {Robert J.} and Juan Politei and Michael Mauer and Alessandro Burlina and Christine Eng and Hopkin, {Robert J.} and Dawn Laney and Ale{\v s} Linhart and Stephen Waldek and Eric Wallace and Frank Weidemann and Wilcox, {William R.}",

note = "Funding Information: The international panels of Fabry disease specialists (Atlanta, GA, USA, July 2014; Orlando, FL, USA, February 2015) were sponsored by Sanofi Genzyme. The authors received editorial/writing support in the preparation of this manuscript from Alessia Piazza, PhD, of Excerpta Medica, funded by Sanofi Genzyme, and from Hans Ebels of Sanofi Genzyme. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication. A.O. was supported by Intensificaci?n FIS and FEDER FundsREDINREN RD016/0019, and D.P.G. by the Plan National Maladies Rares of the French Ministry of Health. Funding Information: The international panels of Fabry disease specialists (Atlanta, GA, USA, July 2014; Orlando, FL, USA, February 2015) were sponsored by Sanofi Genzyme. The authors received editorial/writing support in the preparation of this manuscript from Alessia Piazza, PhD, of Excerpta Medica, funded by Sanofi Genzyme, and from Hans Ebels of Sanofi Genzyme. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication. A.O. was supported by Intensificaci{\'o}n FIS and FEDER Funds REDINREN RD016/0019 , and D.P.G. by the Plan National Maladies Rares of the French Ministry of Health . Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

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AU - Mauer, Michael

AU - Burlina, Alessandro

AU - Eng, Christine

AU - Hopkin, Robert J.

AU - Laney, Dawn

AU - Linhart, Aleš

AU - Waldek, Stephen

AU - Wallace, Eric

AU - Weidemann, Frank

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N2 - Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the “classic” phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. However, much of the current literature reports outcomes after late initiation of ERT, once substantial organ damage has already occurred. Updated monitoring and treatment guidelines for pediatric patients with Fabry disease have recently been published. Expert physician panels were convened to develop updated, specific guidelines for adult patients. Management of adult patients depends on 1) a personalized approach to care, reflecting the natural history of the specific disease phenotype; 2) comprehensive evaluation of disease involvement prior to ERT initiation; 3) early ERT initiation; 4) thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients; 5) use of adjuvant treatments for specific disease manifestations; and 6) management by an experienced multidisciplinary team.

AB - Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the “classic” phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns. Enzyme replacement therapy (ERT) and adjunctive treatments can provide significant clinical benefit. However, much of the current literature reports outcomes after late initiation of ERT, once substantial organ damage has already occurred. Updated monitoring and treatment guidelines for pediatric patients with Fabry disease have recently been published. Expert physician panels were convened to develop updated, specific guidelines for adult patients. Management of adult patients depends on 1) a personalized approach to care, reflecting the natural history of the specific disease phenotype; 2) comprehensive evaluation of disease involvement prior to ERT initiation; 3) early ERT initiation; 4) thorough routine monitoring for evidence of organ involvement in non-classic asymptomatic patients and response to therapy in treated patients; 5) use of adjuvant treatments for specific disease manifestations; and 6) management by an experienced multidisciplinary team.

KW - Diagnosis

KW - Fabry disease

KW - Management

KW - Mutation

KW - Treatment

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Fabry disease revisited: Management and treatment recommendations for adult patients

Abstract

Bibliographical note

Keywords

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