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Cited by 731

The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.

Elevated globotriaosylsphingosine is a hallmark of Fabry disease

Open access
Aerts, Johannes M., Groener, Johanna E., Kuiper, Sijmen, Donker-Koopman, Wilma E., Strijland, Anneke, Ottenhoff, Roelof, van Roomen, Cindy, Mirzaian, Mina, Wijburg, Frits A., Linthorst, Gabor E., Vedder, Anouk C., Rombach, Saskia M., Cox-Brinkman, Josanne, Somerharju, Pentti, Boot, Rolf G., Hollak, Carla E., Brady, Roscoe O., Poorthuis, Ben J.·2008·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0712309105
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Abstract

Fabry disease is an X-linked lysosomal storage disease caused by deficiency of α-galactosidase A that affects males and shows disease expression in heterozygotes. The characteristic progressive renal insufficiency, cardiac involvement, and neuropathology usually are ascribed to globotriaosylceramide accumulation in the endothelium. However, no direct correlation exists between lipid storage and clinical manifestations, and treatment of patients with recombinant enzymes does not reverse several key signs despite clearance of lipid from the endothelium. We therefore investigated the possibility that globotriaosylceramide metabolites are a missing link in the pathogenesis. We report that deacylated globotriaosylceramide, globotriaosylsphingosine, and a minor additional metabolite are dramatically increased in plasma of classically affected male Fabry patients and plasma and tissues of Fabry mice. Plasma globotriaosylceramide levels are reduced by therapy. We show that globotriaosylsphingosine is an inhibitor of α-galactosidase A activity. Furthermore, exposure of smooth muscle cells, but not fibroblasts, to globotriaosylsphingosine at concentrations observed in plasma of patients promotes proliferation. The increased intima-media thickness in Fabry patients therefore may be related to the presence of this metabolite. Our findings suggest that measurement of circulating globotriaosylsphingosine will be useful to monitor Fabry disease and may contribute to a better understanding of the disorder.

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Metadata

Authors
Aerts, J. M., Groener, J. E., Kuiper, S., Donker-Koopman, W. E., Strijland, A., Ottenhoff, R., van Roomen, C., Mirzaian, M., Wijburg, F. A., Linthorst, G. E., Vedder, A. C., Rombach, S. M., Cox-Brinkman, J., Somerharju, P., Boot, R. G., Hollak, C. E., Brady, R. O., & Poorthuis, B. J.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2008-02-26
Volume
105
Issue
8
Pages
2812-2817
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0712309105
OpenAlex
W2097776291
Cited by
731
References
35
FWCI
20.51
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Elevated globotriaosylsphingosine is a hallmark of Fabry disease. https://app.cochat.ai/papers/10.1073/pnas.0712309105
The paper
Aerts, J. M., Groener, J. E., Kuiper, S., Donker-Koopman, W. E., Strijland, A., Ottenhoff, R., van Roomen, C., Mirzaian, M., Wijburg, F. A., Linthorst, G. E., Vedder, A. C., Rombach, S. M., Cox-Brinkman, J., Somerharju, P., Boot, R. G., Hollak, C. E., Brady, R. O., & Poorthuis, B. J. (2008). Elevated globotriaosylsphingosine is a hallmark of Fabry disease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0712309105

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.