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Case Reports
. 2021 Dec 14;14(12):1304.
doi: 10.3390/ph14121304.

Migalastat Treatment in a Kidney-Transplanted Patient with Fabry Disease and N215S Mutation: The First Case Report

Valeria Di Stefano  1   2 , Marta Mancarella  3 , Antonia Camporeale  4 , Anna Regalia  5 , Marta Ferraresi  1   2 , Marco Pisaniello  6 , Elena Cassinerio  1 , Federico Pieruzzi  7   8 , Irene Motta  1   2
Affiliations
Case Reports

Migalastat Treatment in a Kidney-Transplanted Patient with Fabry Disease and N215S Mutation: The First Case Report

Valeria Di Stefano et al. Pharmaceuticals (Basel). .

Abstract

Fabry disease is a rare X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to deficient α-galactosidase A activity and, consequently, to glycosphingolipid accumulation in a wide variety of cells. Fabry disease due to N215S (c.644A>G, p.Asn215Ser) missense mutation usually results in a late-onset phenotype presenting with isolated cardiac involvement. We herein present the case of a patient with N215S mutation with cardiac involvement, namely left ventricular hypertrophy and ventricular arrhythmias, and end-stage renal disease requiring kidney transplantation. To the best of our knowledge, this is the first report of a kidney-transplanted Fabry patient treated with oral pharmacologic chaperone migalastat.

Keywords: Fabry disease; GLA; N215S; cardiac variant; hypertrophic cardiomyopathy; kidney transplant; late-onset phenotype; migalastat.

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Conflict of interest statement

AC received honoraria for lectures and board meetings from Amicus Therapeutics, Sanofi Genzyme, and Takeda-Shire, and a research grant from Amicus Therapeutics. FP received educational and travel grants, and is an advisory board member of Sanofi Genzyme, Takeda, Amicus Therapeutics, and Chiesi Farmaceutici S.p.A. IM received lecture honoraria for lectures from Sanofi Genzyme and is a member of the advisory boards of Sanofi Genzyme and Amicus. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cardiac magnetic resonance findings. Cine (a) and late gadolinium enhancement images (b), T2 (c), and T1 map (d) in basal short-axis view. Significant biventricular hypertrophy with extensive late gadolinium enhancement in the infero-lateral wall ((b), red arrow). Increased T2 values in the infero-lateral wall ((c), black arrow) indicate myocardial inflammation. Reduced native T1 values (d), suggesting myocardial glycosphingolipid storage, are a typical finding in Fabry disease.
Figure 2
Figure 2
Transmission electron microscopy image of the kidney biopsy (10 × 3000), showing a multivacuolized appearance of a podocyte (pod). Since the analysis in electron microscopy was carried out on a fragment of renal tissue recovered from paraffin (and not on a standard glutaraldehyde fixed preparation), the overall structural detail was poorly preserved, and glycosphingolipid deposits could not be directly visualized due to the extraction of the lipid components. This resulted in a multivacuolized appearance of the podocytes that, although not strictly diagnostic, was compatible with the diagnosis of Fabry disease.
See this image and copyright information in PMC

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