Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis

Gaspar P, Kallemeijn WW, Strijland A, Scheij S, Van Eijk M, Aten J, Overkleeft HS, Balreira A, Zunke F, Schwake M, Miranda CS, et al. (2014)
The Journal of Lipid Research 55(1): 138-145.

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Abstract
Lysosomal integral membrane protein-2 (LIMP2) mediates trafficking of glucocerebrosidase (GBA) to lysosomes. Deficiency of LIMP2 causes action myoclonus-renal failure syndrome (AMRF). LIMP2-deficient fibroblasts virtually lack GBA like the cells of patients with Gaucher disease (GD), a lysosomal storage disorder caused by mutations in the GBA gene. While GD is characterized by the presence of glucosylceramide-laden macrophages, AMRF patients do not show these. We studied the fate of GBA in relation to LIMP2 deficiency by employing recently designed activity-based probes labeling active GBA molecules. We demonstrate that GBA is almost absent in lysosomes of AMRF fibroblasts. However, white blood cells contain considerable amounts of residual enzyme. Consequently, AMRF patients do not acquire lipid-laden macrophages and do not show increased plasma levels of macrophage markers, such as chitotriosidase, in contrast to GD patients. We next investigated the consequences of LIMP2 deficiency with respect to plasma glycosphingolipid levels. Plasma glucosylceramide concentration was normal in the AMRF patients investigated as well as in LIMP2-deficient mice. However, a marked increase in the sphingoid base, glucosylsphingosine, was observed in AMRF patients and LIMP2-deficient mice. Our results suggest that combined measurements of chitotriosidase and glucosylsphingosine can be used for convenient differential laboratory diagnosis of GD and AMRF.
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Gaspar P, Kallemeijn WW, Strijland A, et al. Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis. The Journal of Lipid Research. 2014;55(1):138-145.
Gaspar, P., Kallemeijn, W. W., Strijland, A., Scheij, S., Van Eijk, M., Aten, J., Overkleeft, H. S., et al. (2014). Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis. The Journal of Lipid Research, 55(1), 138-145.
Gaspar, P., Kallemeijn, W. W., Strijland, A., Scheij, S., Van Eijk, M., Aten, J., Overkleeft, H. S., Balreira, A., Zunke, F., Schwake, M., et al. (2014). Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis. The Journal of Lipid Research 55, 138-145.
Gaspar, P., et al., 2014. Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis. The Journal of Lipid Research, 55(1), p 138-145.
P. Gaspar, et al., “Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis”, The Journal of Lipid Research, vol. 55, 2014, pp. 138-145.
Gaspar, P., Kallemeijn, W.W., Strijland, A., Scheij, S., Van Eijk, M., Aten, J., Overkleeft, H.S., Balreira, A., Zunke, F., Schwake, M., Miranda, C.S., Aerts, J.M.F.G.: Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis. The Journal of Lipid Research. 55, 138-145 (2014).
Gaspar, Paulo, Kallemeijn, Wouter W., Strijland, Anneke, Scheij, Saskia, Van Eijk, Marco, Aten, Jan, Overkleeft, Herman S., Balreira, Andrea, Zunke, Friederike, Schwake, Michael, Miranda, Clara Sa, and Aerts, Johannes M. F. G. “Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis”. The Journal of Lipid Research 55.1 (2014): 138-145.
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