Niemann-Pick disease types A and

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

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]. 

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... 

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. 

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]. 

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. 

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. 

Alvelius, G., Hjalmarson, O., Griffiths, W. J., Bjorkhem, L, and Sjovall, J. 2001. Identification of unusual 7-oxygenated bile acid sulfates in a patient with Niemann-Pick disease, type C. J. Lipid Res. 42 1571-7. 

Horinouchi K, Erlich S, Perl DP, Ferlinz K, Bisgaier CL, Sandhoff K, Desnick RJ, Stewart CL, Schuchman EH. Acid sphingomyelinase deficient mice a model of types A and B Niemann-Pick disease. Nat Genet 1995 10(3) 288-93. 

Niemann-Pick diseases. These are also classified as lysosomal storage diseases. There are two main distinct sub-families type A (NP-A) and type B (NP-B), both caused by defects in the acid sphingomyelinase gene. Further type C diseases are caused by defects in a gene involved in LDL-cholesterol homeostasis, identified as the NPCl gene. 

For disorders characterized by an underlying enzyme deficiency (e.g., Gaucher disease, Fabry disease, Tay-Sachs, Hurler syndrome), assays of enzyme activity in blood and/or tissues is generally available (Meikle et al., 2004). Mutation analysis is also available, particularly for populations in whom the common disease alleles are known (e.g., mutations among Ashkenazi Jews for Gaucher, Tay-Sachs, Niemann-Pick type A, and mucolipidosis type IV Ostrer, 2001). In other cases, analysis of the gene defect responsible for rare subtypes is available through specialized laboratories. 

Type E is also known as the sea-blue histiocytes syndrome and is considered to be a special form of Niemann-Pick disease found in adults. The stored, ceroid-like, acid-proof and PAS-positive pigment shows a sea-blue colour on Giemsa staining. Hepatosplenomegaly is present thrombopenia is likewise in evidence due to bone marrow involvement. Cirrhosis may develop. The prognosis is considered to be good. (243)... 

McGovern MM, Pohl-Worgall T, Deckelbaum RJ, Simpson W, Mendelson D, Desnick RJ, Schuchman EH, Wasserstein MP. Lipid abnormalities in children with types A and B Niemann Pick disease. J Pediatr 145(2004) 77-81. 

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