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Effects of switching from agalsidase-α to agalsidase-β on biomarkers, renal and cardiac parameters, and disease severity in fabry disease forming neutralizing antidrug antibodies: a case report.
- Source :
-
CEN case reports [CEN Case Rep] 2024 Aug; Vol. 13 (4), pp. 290-296. Date of Electronic Publication: 2023 Dec 22. - Publication Year :
- 2024
-
Abstract
- Fabry disease is an X-linked hereditary disorder caused by deficient α-galactosidase A (GLA) activity. Patients with Fabry disease are often treated with enzyme replacement therapy (ERT). However, ERT often induces the formation of neutralizing antidrug antibodies (ADAs), which may impair the therapeutic efficacy. Here, we report the case of a 32-year-old man with Fabry disease and resultant neutralizing ADAs who was treated by switching from agalsidase-α to agalsidase-β. We monitored biomarkers, such as plasma globotriaosylsphingosine (lyso-Gb3), urinary globotriaosylceramide (Gb3), urinary mulberry bodies, renal and cardiac parameters, and disease severity during the treatment period. Although plasma lyso-Gb3 and urinary Gb3 levels quickly decreased within two months after the initiation of ERT with agalsidase-α, they gradually increased thereafter. The urinary mulberry bodies continued to appear. Both the ADA titer and serum mediated GLA inhibition rates started to increase after two months. Moreover, 3.5 years after ERT, the vacuolated podocyte area in the renal biopsy decreased slightly from 23.1 to 18.9%. However, plasma lyso-Gb3 levels increased, and urinary Gb3, mulberry body levels, and ADA titers remained high. Therefore, we switched to agalsidase-β which reduced, but did not normalize, plasma lyso-Gb3 levels and stabilized renal and cardiac parameters. Disease severity was attenuated. However, urinary Gb3 and mulberry body levels did not decrease noticeably in the presence of high ADA titers. The kidneys take up a small amount of the administered recombinant enzyme, and the clearance of Gb3 that has accumulated in the kidney may be limited despite the switching from agalsidase-α to agalsidase-β.<br /> (© 2023. The Author(s), under exclusive licence to Japanese Society of Nephrology.)
- Subjects :
- Humans
Male
Adult
Glycolipids
Kidney pathology
Severity of Illness Index
Treatment Outcome
Recombinant Proteins
Fabry Disease drug therapy
Fabry Disease diagnosis
alpha-Galactosidase therapeutic use
alpha-Galactosidase administration & dosage
alpha-Galactosidase immunology
Biomarkers blood
Enzyme Replacement Therapy methods
Isoenzymes therapeutic use
Isoenzymes administration & dosage
Antibodies, Neutralizing blood
Trihexosylceramides urine
Sphingolipids blood
Subjects
Details
- Language :
- English
- ISSN :
- 2192-4449
- Volume :
- 13
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- CEN case reports
- Publication Type :
- Academic Journal
- Accession number :
- 38135868
- Full Text :
- https://doi.org/10.1007/s13730-023-00843-1