• Nephrol. Dial. Transplant. · Jun 2021

    Review

    Precision medicine in Fabry disease.

    • Malte Lenders and Eva Brand.
    • Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, Interdisciplinary Fabry Center Münster, University Hospital Münster, Münster, Germany.
    • Nephrol. Dial. Transplant. 2021 Jun 22; 36 (Suppl 2): 14-23.

    AbstractFabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A (GLA) gene, leading to a deficiency in α-galactosidase A. The lysosomal accumulation of glycosphingolipids, primarily globotriaosylceramide (Gb3) and its deacylated form, globotriaosylsphingosine (lyso-Gb3), results in progressive renal failure, cardiomyopathy associated with cardiac arrhythmia and recurrent cerebrovascular events, significantly limiting life expectancy in affected patients. In male patients, a definitive diagnosis of FD involves demonstrating a GLA deficiency in leucocytes. In females, because of the potential high residual enzymatic activity, the diagnostic gold standard requires molecular genetic analyses. The current treatment options for FD include recombinant enzyme replacement therapies (ERTs) with intravenous agalsidase-α (0.2 mg/kg body weight) or agalsidase-β (1 mg/kg body weight) every 2 weeks as well as an oral pharmacological chaperone (migalastat 123 mg every other day) that selectively and reversibly binds to the active sites of amenable mutant forms of the GLA enzyme. These therapies facilitate cellular Gb3 clearance and an overall improvement of disease burden. However, ERT can lead to infusion-associated reactions, as well as the formation of neutralizing anti-drug antibodies in ∼40% of all ERT-treated males, leading to an attenuation of therapy efficacy. This article reviews the clinical presentation, diagnosis and interdisciplinary clinical management of FD and discusses the therapeutic options, with a special focus on precision medicine, accounting for individual variability in genetic mutations, Gb3 and lyso-Gb3 levels, allowing physicians to predict more accurately which prevention and treatment strategy is best for which patient.© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…

What will the 'Medical Journal of You' look like?

Start your free 21 day trial now.

We guarantee your privacy. Your email address will not be shared.