Progress in the understanding and treatment of Fabry disease. Biochim Biophys Acta Gen Subj 2020 Jan;1864(1):129437
Date
09/19/2019Pubmed ID
31526868Pubmed Central ID
PMC6981246DOI
10.1016/j.bbagen.2019.129437Scopus ID
2-s2.0-85073720962 (requires institutional sign-in at Scopus site) 68 CitationsAbstract
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.
Author List
Miller JJ, Kanack AJ, Dahms NMAuthor
Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsDisease Models, Animal
Enzyme Replacement Therapy
Fabry Disease
Glycosphingolipids
Humans
Lysosomal Storage Diseases
RNA, Messenger
alpha-Galactosidase
