Metabolic abnormalities in feline Niemann-Pick type C heterozygotes

D. E. Brown, M. A. Thrall, S. U. Walkley, S. Wurzelmann, D. A. Wenger, R. W. Allison, C. A. Just

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28 Scopus citations

Abstract

Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral lysosomal storage disorder in which cholesterol lipidosis results from defective intracellular transport of unesterified cholesterol. The primary molecular defect of NPC is unknown; regulatory mechanisms of cholesterol metabolism are impaired, resulting in retarded esterification of exogenous cholesterol with accumulation of unesterified cholesterol in lysosomes and secondary storage of glycolipids and sphingomyelin. In obligate heterozygotes from a feline NPC model, cultured skin fibroblasts challenged with exogenously derived cholesterol exhibited intermediate rates of cholesterol esterification and accumulation of unesterified cholesterol. Liver lipid analyses of obligate heterozygote cats demonstrated intermediate cholesterol and sphingomyelin concentrations. Vacuolated skin fibroblasts were found in 2 of 3 heterozygote cats, and occasional cortical neurons exhibited intracellular inclusions immunoreactive for GM2-ganglioside. Ultrastructural studies provided evidence of storage in liver and brain. We believe these morphological and biochemical findings are the first example of manifestations of CNS abnormalities in a genetic carrier for a neuronal storage disease.

Original languageEnglish (US)
Pages (from-to)319-330
Number of pages12
JournalJournal of Inherited Metabolic Disease
Volume19
Issue number3
DOIs
StatePublished - Jul 1 1996

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Brown, D. E., Thrall, M. A., Walkley, S. U., Wurzelmann, S., Wenger, D. A., Allison, R. W., & Just, C. A. (1996). Metabolic abnormalities in feline Niemann-Pick type C heterozygotes. Journal of Inherited Metabolic Disease, 19(3), 319-330. https://doi.org/10.1007/BF01799262