Niemann-Pick disease Type

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

NPC1 Niemann-Pick disease type Cl, NPC2 Niemann-Pick disease type C2, OMIM Online Mendelian Inheritance in Man, P plasma, U urine... 

This enzyme is increased in Gaucher disease and may also be increased, but to a lesser extent, in other sphingolipidoses such as Niemann-Pick disease type A/ and NPC, Krabbe disease, and GM1-gangliosidosis. The assay is based on the method described by Hollak et al. [22] and Guo et al. [17]. 

This enzyme is deficient in Niemann-Pick disease type A/ (Table 4.4.1, Fig. 4.4.1). The assay with radioactive natural substrate is based on the method described by Wenger [59]. The assay with fluorescent substrate is based on the method described by van Diggelen et al. [54]. These assays have not yet been validated in the authors laboratory for use with dried blood spots. For this application the reader is referred to Chamoles et al. [9]. 

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... 

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]. 

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... 

Sphingomyelin Niemann-Pick disease types A tind B Sphingomyelinase llpl5.1-15.4... 

Cholesterol, sphingomyelin, GM2-gangliosides G. Monosaccraides/amino acid/monomers Niemann-Pick disease type C NPC1 HE1 18qll-12 14q24.3... 

Birch, N.C., Radio, S., Horslen, S. Metastatic hepatocellular carcinoma in a patient with Niemann-Pick disease, type C. J. Pediatr. Gastroenterol. Nutr. 2003 37 624-626... 

K. Treatment of Niemann-Pick disease type B by allogeneic bone marrow transplantation. Brit. Med. J. 1987 295 1375-1376... 

Yerusalem, B., Sokol, R.J., Narkewicz, M.R., Smith, D., Ashmead, J.W., Wenger, D.A. Niemann-Pick disease type C in neonatal cholestasis at a North American center. J. Pediatr. Gastroenterol. Nutrit. 2002 35 44-50... 

Niemann-Pick disease type C—A cholesterol storage disease... 

Vanier MT, Pentchev P, Rodriguez-Lafrasse C, et al. (1991) Niemann—Pick disease type C an update. J Inherit Metab Dis 14 580-595... 

Of the four subtypes of Niemann-Pick disease, type A is the most severe. It is inherited as a recessive disorder (i.e., a defective copy of the gene must be inherited from each parent) that results in an absence of the enzyme sphingomyelinase. The absence of this enzyme causes the storage of large amounts of sphingomyelin and cholesterol in the brain, bone marrow, liver, and spleen. 

Schuchmann EH, Desnick RJ Niemann-Pick Diseases Type A and B Acid sphingomyelinase deficiencies, Vol. 2. New York McGraw Hill (1995) 2601-2624. 

Lachmann, R. H., Te Vruchte, D., Lloyd-Evans, E., Reinkensmeier, G., Sillence, D. J., Fernandez-Guillen, L., Dwek, R. A., Butters, T. D., Cox, T. M., and Platt, F. M., Treatment with miglustat reverses the lipid-trafficking defect in Niemann-Pick disease type C, Neurobiol Dis 16 (2004) 654-658. 

Winsor, E. J., and Welch, J. P., Genetic and demographic aspects of Nova Scotia Niemann-Pick disease (type D), Am J Hum Genet 30 (1978) 530-538. 

Importantly, March and co-workers (Lee et al., 2006) recently reported that increased sphingomyelin content impairs high-density lipoprotein (HDL) biogenesis and maturation in human Niemann-Pick disease type B patients which feature highly reduced ASMase activity. Since HDL is atheroprotective, it... 

Lee, C.Y., Lesimple, A., Denis, M., Vincent, J., Larsen, A., Mamer, O., Krimbou, L., Genest, J., and Marcil, M., Increased sphingomyelin content impairs HDL biogenesis and maturation in human Niemann-Pick disease type B, J Lipid Res, 47 (2006) 622-632. 

Patterson, M.C., Vanier, M.T., Suzuki, K., Morris, J.A., Carstea, E., Neufeld, E.B., Blanchette-Mackie, J.E., Pentchev, P.G. 2001. Niemann-Pick disease type C a lipid trafficking disorder. In The Metabolic and Molecular Bases of Inherited Disease. C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle, editors. New York McGraw-Hill, pp. 3611-3633. 

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