Niemann-Pick C disease

Patterson MC, Vecchio D, Prady H, Abel L, Wraith JE. Miglustat for treatment of Niemann-Pick C disease a randomised controlled study. Lancet Neurol. 2007 6 765-772. 

Vance, J. E. Lipid imbalance in the neurological disorder, Niemann-Pick C disease. FEBS Lett 580 (2006) 5518-5524. 

Bis(monoacylglycero)phosphate (BMP) species are isomeric to PG species. In BMP, two FA chains are acylated to different glycerol molecules, whereas these FA chains are located in one glycerol in PG species. BMP plays an important role in normal lysosomal/endosomal functions in cells [62]. It has become evident that BMP is involved in the pathology of lysosomal storage diseases such as Niemann-Pick C disease (cholesterol accumulation) and certain drug-induced lipidoses [63,64]. Dys-regulation of BMP metabolism and hence of cholesterol homeostasis may also be relevant to atherosclerosis [64]. 

Bartsch, G. The nature of the lipids in the brain in Niemann-Pick s disease. In Cerebral lipidoses. A Symposium (Cumings, J.N., and Low-enthal. A., eds.), p. 159-163. Springfield, Illinois Charles C.Thomas Publisher 1957... 

Niemann-Pick disease C type 2 Gmj activator protein deficiency Sphingolipid activator protein deficiency... 

Neuronal ceroid lipofuscinosis (CNL5) Danon s disease (LAMP-2 deficiency) Niemann-Pick disease C type 1 Cystinosis... 

MCI mild cognitive impairment NPC Niemann-Pick disease type C... 

Cholesterol storage in lysosomes/endosomes is a hallmark of Niemann-Pick type C disease. The assay is based on the procedure described by Vanier et al. [58]. 

Chamoles NA, Blanco M, Gaggiolo D, Casentini C (2002) Gaucher and Niemann-Pick diseases - enzymatic diagnosis in dried blood spots on filter paper retrospective diagnoses in newborn-screening cards. Clin Chim Acta 317 191-197... 

Pentchev PG, Comly ME, Kruth HS, Vanier MT, Wenger DA, Patel S, Brady RO (1985) A defect in cholesterol esterification in Niemann-Pick disease (type C) patients. Proc Natl Acad Sci U S A 82 8247-8251... 

Ries M, Schaefer E, Liihrs T, Mani L, Kuhn J, Vanier MT, Krummenauer F, Gal A, Beck M, Mengel E (2006) Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/ and C. J Inherit Metab Dis 29 647-652... 

Vanier MT, Rodriguez-Lafrasse C, Rousson R, Gazzah N, Juge M-C, Pentchev PG, Revol A, Louisot P (1991) Type C Niemann-Pick disease spectrum of phenotypic variation in disruption of intracellular LDL-derived cholesterol processing. Biochim Biophys Acta 1096 328-337... 

However, very low plasma levels of HDL cholesterol are also found in patients with genetically disturbed metabolic pathways that are indirectly linked to HDL metabolism. For example, many patients with lipid storage diseases like Gaucher s disease (glucocerobrosidase deficiency, OMIM 230800-231000), Nieman-Pick disease types A or (sphingomyelinase deficiency, OMIM 257200 and 607616, respectively), Niemann-Pick disease type C (OMIM 257220), hypertriglyceridemia, or diabetes mellitus present with low HDL cholesterol [22]. 

Niemann-Pick disease. Kolodny, E.H. (2000). Curr Opin Hematol, 7 1 48-52. [647919] Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology. Shihabuddin, L.S., Numan, S., Huff, M.R., Dodge, J.C., Clarke, J., Macauley, S.L., Yang, W., Taksir, T.V., Parsons, G., Passini, M.A., Gage, F.H., Stewart, G.R. (2004). J Neurosci, 24 (47) 10642-10651. 

The receptors can be recycled, whereas the lipoprotein remnants in the vesicle are transferred to lysosomes and degraded by lysosomal (hydrolytic) enzymes, releasing free cholesterol, amro acids, fatty acids, and phospholipids. These compounds can be reutilized by the cell. [Note Rare autosomal recessive deficiencies in the ability to hydrolyze lysosomal cholesteryl esters (Wolman disease), or to transport unesterified cholesterol out of the lyso some (Niemann-Pick disease, type C) have been identified.]... 

Vankova J, Stepanova J, Jech R, Elleder M, Ling L, Mignot E, Nishino S, Nevsimalova S (2003) Sleep disturbances and hypocretin deficiency in Niemann-Pick disease type C. Sleep 26 427-430... 

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