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Acta Neuropathologica

, Volume 66, Issue 4, pp 325–336 | Cite as

Niemann-Pick disease type C

Study on the nature of the cerebral storage process
  • M. Elleder
  • A. Jirásek
  • F. Šmíd
  • J. Ledvinová
  • G. T. N. Besley
Original Works

Summary

A complex neuropathological study of two cases of Niemann-Pick disease (NPD) type C (NPDC) revealed some novel features in the chemical pathology of the neuronal storage. Lipid histochemistry showed the presence of a lipid which met the criteria of a neuronal glycosphingolipid. Sphingomyelin (SM) was not detected in the neurones in any of the regions examined. Lipid chemical analysis of total extracts and of partially purified lysosomal fraction of the brain cortex showed markedly increased levels of neutral ceramide hexosides especially of glucosylceramide and ceramide dihexoside (mostly of its slower band). Phospholipids were not significantly increased. Monosialogangliosides GM2 and GM3 were increased only slightly. The storage process displayed the well known fine structure and was accompanied by a marked secondary increase in some lysosomal enzyme activities. There was neuroaxonal dystrophy (NAD) of considerable intensity and extent. Many spheroids contianed masses of degenerated organelles and neurofilaments in various proportions and displayed variable activities of acid phosphatase, nonspecific esterase and dehydrogenases. There was marked brain atrophy accompanied in one case by severe demyelination. Enzyme studies revealed partial decrease of sphingomyelinase (SMase) and betaglucosidase activities in cultured fibroblasts, as well as lack of cathodic SMase activity on isoelectric focusing. No defects of these enzymes were found in the brain samples. The findings are regarded as significant since they indicate a biochemical defect in which SM is not primarily involved and which may thus be fundamentally different from that in type A of NPD.

Key words

Niemann-Pick disease type C Neuronal storage Sphingomyelin Neutral glycosphingo-lipids Sphingomyelinase 

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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • M. Elleder
    • 1
  • A. Jirásek
    • 1
  • F. Šmíd
  • J. Ledvinová
    • 2
  • G. T. N. Besley
    • 3
  1. 1.Hlava's Institute of Pathological AnatomyCharles University Medical FacultyPragueCzechoslovakia
  2. 2.Laboratory for ProteosynthesisCharles University Medical FacultyPragueCzechoslovakia
  3. 3.Dept. of Genetic PathologyHospital for Sick ChildrenEdinburgh

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