Abstract
Background
Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase enzyme deficiency. We present clinical, biochemical, and histologic findings in children with classical phenotypic presentation of Fabry disease.
Methods
A retrospective analysis was performed using charts from 14 children with confirmed diagnosis. Clinical parameters were evaluated. Globotriaosylsphingosine -lysoGb3- detection in plasma, podocyturia, and kidney biopsy were carried out in all cases.
Results
All patients except one demonstrated at least one symptom of Fabry disease. LysoGb3 levels were above the normal range in all patients. Podocyturia was documented in all patients. Kidney biopsy revealed glomerular, interstitial, vascular, and tubular changes on light microscopy in nearly all patients. Electron microscopy showed podocyte inclusions in all patients.
Conclusions
No difference in symptomatology was discernible between boys and girls. Podocyturia was detectable in children serving as a possible early marker of kidney injury. LysoGb3 was elevated in all cases, emphasizing the importance for diagnosis especially in female patients with normal αGal A activity. A possible association between lysoGb3 and symptom severity and histological involvement in kidney biopsy should be assessed in prospective studies with enough statistical power to determine if lysoGb3 can be used to predict nephropathy in children with Fabry disease.
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Consuelo Durand, Juan Politei, Andrea Schenone, and Hernan Trimarchi conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript.
Joaquin Frabasil and Dana Velasques Rivas measured lyaoGb3, critically reviewed the genotype-phenotype relation in all patients, and revised the manuscript.
Oscar Amoreo, Maria Nieves Arán, Marcelo Barán, Silvia Di Pietrantonio, and Miguel Liern took the kidney biopsies and revised the manuscript.
Valeria Alberton, Roberto Iotti, and Fernanda Toniolo analyzed and informed the kidney biopsies and revised the manuscript.
Norberto Antongiovanni, Gustavo Cabrera, Consuelo Durand, Alejandro Fainboim, Fernando Gomez Pizarro, Fernando Perretta, Diego Ripeau, and Eric Wallace drafted the initial manuscript and reviewed and revised the manuscript.
All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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This study was conducted in accordance with the principles of the Helsinki Declaration.
Conflict of interest
Juan Politei received honoraria for lectures on Fabry disease from Sanofi Genzyme, Shire HGT, Amicus, Actelion, and Protalix. Consuelo Durand, Alejandro Fainboim, Andrea Beatriz Schenone received honoraria for lectures from Sanofi Genzyme and Biomarin. Hernan Trimarchi received honoraria for lectures on Fabry disease from Sanofi Genzyme. The other authors have no conflicts of interest to disclose.
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Politei, J., Alberton, V., Amoreo, O. et al. Clinical parameters, LysoGb3, podocyturia, and kidney biopsy in children with Fabry disease: is a correlation possible?. Pediatr Nephrol 33, 2095–2101 (2018). https://doi.org/10.1007/s00467-018-4006-3
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DOI: https://doi.org/10.1007/s00467-018-4006-3