Abstract
Fabry disease is an X-linked glycosphingolipidosis caused by deficient synthesis of the enzyme α-galactosidase A, which results in accumulations of globotriaosylceramide (GL-3) in systemic tissues. Nephropathy is a dominant feature of Fabry disease. It still remains unclear how the nephropathy progresses. Recombinant agalsidase replacement therapy is currently the only approved, specific therapy for Fabry disease. The optimal dose of replacement enzyme also still remains unclear. The worldwide shortage of agalsidase-β in 2009 forced dose reduction of administration. It showed that the proteinuria emerged like surges, followed by temporary plasma GL-3 elevations in the early stages of classic Fabry disease. Additionally, it also showed that 1 mg/kg of agalsidase-β every other week could clear the GL-3 accumulations from podocytes and was required to maintain negative proteinuria and normal plasma GL-3 levels.
Conclusion: This observation of a young patient with classic Fabry disease about 5 years reveals that the long-term, low-dose agalsidase-β caused proteinuria surges, but not persistent proteinuria, followed by temporary plasma GL-3 elevations, and agalsidase-β at 1 mg/kg every other week could clear accumulated GL-3 from podocytes and was required to maintain normal urinalysis and plasma GL-3 levels.
What is Known: • Patients with Fabry disease show GL-3 accumulations in podocytes and foot process effacement without proteinuria. • The optimal dose of replacement enzyme (agalsidase-α or -β) remains unclear. |
What is New: • The long-term, low-dose agalsidase-β caused proteinuria surge, but not persistent proteinuria, followed by temporary plasma GL-3 elevations • Agalsidase-β at 1 mg/kg every other week could clear accumulated GL-3 from podocytes, and was required to maintain normal urinalysis and normal plasma GL-3 levels. |
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Abbreviations
- EOW:
-
Every other week
- GL-3:
-
Globotriaosylceramide
- UCr:
-
Urinary creatinine
- UP:
-
Urinary protein
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Author’s contributions
Dr. Kanai was the author of this manuscript and the physician in charge of the patient; Prof. Yamagata acted as an advisor for this study; Dr. Ito, Dr. Odaka, Dr. Saito, Dr. Aoyagi, and Dr. Betsui assisted in treating the patient.
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Dr. Kanai received speaking fee, ¥ 500,00 yen, on “Foot process effacement with normal urinalysis in classic Fabry disease. JIMD reports 1:39-42” from Genzyme co. Other authors declare no financial relationships that could be relevant to this work.
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All applicable national and institutional guidelines for the care were followed. All procedures performed in this study were accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments.
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Witten informed consent was obtained from the patient and his parent.
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Communicated by Beat Steinmann
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Kanai, T., Ito, T., Odaka, J. et al. Surges in proteinuria are associated with plasma GL-3 elevations in a young patient with classic Fabry disease. Eur J Pediatr 175, 427–431 (2016). https://doi.org/10.1007/s00431-015-2646-x
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DOI: https://doi.org/10.1007/s00431-015-2646-x