Progress in the Understanding and Treatment of Fabry Disease

Overview

Journal Biochim Biophys Acta Gen Subj

Publisher Elsevier

Specialties Biochemistry
Biophysics

Date 2019 Sep 19

PMID 31526868

Citations 47

Authors

James J Miller

Adam J Kanack

Nancy M Dahms

Affiliations

Soon will be listed here.

Abstract

Background: Fabry disease is caused by α-galactosidase A deficiency. Substrates of this lysosomal enzyme accumulate, resulting in cellular dysfunction. Patients experience neuropathic pain, kidney failure, heart disease, and strokes.

Scope Of Review: The clinical picture and molecular features of Fabry disease are described, along with updates on disease mechanisms, animal models, and therapies.

Major Conclusions: How the accumulation of α-galactosidase A substrates, mainly glycosphingolipids, leads to organ damage is incompletely understood. Enzyme replacement and chaperone therapies are clinically available to patients, while substrate reduction, mRNA-based, and gene therapies are on the horizon. Animal models exist to optimize these therapies and elucidate disease mechanisms for novel treatments.

General Significance: Recent newborn screening studies demonstrate that Fabry disease is the most common lysosomal storage disease. As many countries now include Fabry disease in their screening panels, the number of identified patients is expected to increase significantly. Better knowledge of disease pathogenesis is needed to improve treatment options.

Citing Articles

Lectin-Based Substrate Detection in Fabry Disease Using the Gb3-Binding Lectins StxB and LecA.

Elcin-Guinot S, Lagies S, Avi-Guy Y, Neugebauer D, Huber T, Schell C Int J Mol Sci. 2025; 26(5).

PMID: 40076891 PMC: 11900420. DOI: 10.3390/ijms26052272.

Health State Utility Values in Fabry Disease: Insights from the Pegunigalsidase Alfa Clinical Trials.

Azimpour K, Dorling P, Koulinska I, Kunduri S, Lan Z, Poritz J Adv Ther. 2025; 42(3):1421-1434.

PMID: 39847314 PMC: 11868215. DOI: 10.1007/s12325-024-03095-2.

Targeted nanoliposomes to improve enzyme replacement therapy of Fabry disease.

Tomsen-Melero J, Molto-Abad M, Merlo-Mas J, Diaz-Riascos Z, Cristobal-Lecina E, Soldevila A Sci Adv. 2024; 10(50):eadq4738.

PMID: 39671483 PMC: 11801267. DOI: 10.1126/sciadv.adq4738.

Influence of Treatment Effect Modifiers in Fabry Disease: A Systematic Literature Review.

Azimpour K, Tordoff-Gibson C, Dorling P, Koulinska I, Kunduri S, Laliman-Khara V Adv Ther. 2024; 42(2):579-596.

PMID: 39636566 PMC: 11787270. DOI: 10.1007/s12325-024-03062-x.

Human Gb3/CD77 synthase: a glycosyltransferase at the crossroads of immunohematology, toxicology, and cancer research.

Szymczak-Kulus K, Czerwinski M, Kaczmarek R Cell Mol Biol Lett. 2024; 29(1):137.

PMID: 39511480 PMC: 11546571. DOI: 10.1186/s11658-024-00658-7.

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