Abstract
Sphingolipidoses are a group of rare genetic disorders caused by a = deficiency in the lysosomal degradation or transport of sphingolipids = i.e. sphingomyelin, ceramide, neutral glycosphingo-lipids and = gangliosides. The enzymes involved in the stepwise degradation of = sphingolipids are exo-hydrolases with optimal activity at acidic pH. A = deficiency of one of these enzymes gives rise to a particular = sphingolipid storage disorder. Since most of the enzymes involved in the = degradation of sphingolipids require an activator protein for activity = in vivo, a deficiency of an activator protein gives rise to a storage = disease with clinical features similar to the disease caused by the = enzyme deficiency. Niemann-Pick disease type C is an exception in that = this complex (glycosphingo-) lipid storage disease is not caused by an = enzyme deficiency, but can be considered as a (glycosphingo-)lipid = trafficking defect caused by a deficiency of one of two proteins NPC1 or = NPC2. Early diagnosis of sphingolipidoses is important for genetic = counselling and implementation of therapy. In most cases a definitive = diagnosis can be established by enzyme activity determinations in = leukocytes, fibroblasts or dried blood spots. In some cases histological = examination of cells, determination of the storage product in plasma or = urine, and mutation analysis are also necessary to reach a final = diagnosis. In this chapter methodology to diagnose the sphingolipidoses = is described and the possible pitfalls are discussed.
Keywords
- Fabry Disease
- Gauche Disease
- Lysosomal Storage Disorder
- Lysosomal Storage Disease
- Metachromatic Leukodystrophy
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Poorthuis, B., Aerts, J. (2008). Glycosphingolipids. In: Blau, N., Duran, M., Gibson, K. (eds) Laboratory Guide to the Methods in Biochemical Genetics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-76698-8_20
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