Niemann-Pick disease, acid sphingomyelinase

NIEMANN-PICK DISEASE ACID SPHINGOMYELINASE DEFICIENCY... 

Niemann-Pick disease Acid sphingomyelinase deficiency Takahashi ei of., 1992... 

Niemann-Pick disease Acid sphingomyelinase Sphingomyebn... 

Miranda, S. R., Erlich, S., Friedrich, V. L., Jr., Gatt, S. and Schuchman, E. H. (2000). Hematopoietic stem cell gene therapy leads to marked visceral organ improvements and a delayed onset of neurological abnormalities in the acid sphingomyelinase deficient mouse model of Niemann-Pick disease. Gene Ther. 7, 1768-1776. 

Acid sphingomyelinase is a lysosomal enzyme that catalyzes the breakdown of sphingomyelin to ceramide and phosphoryl-choline.A deficiency of this enzyme leads to lysosomal accumulation of sphingomyelin in patients with Niemann-Pick disease. Recent data indicate that correct intracellular targeting of acid sphingomyelinase to lysosomes is dependent on the mannose 6-phosphate-mediated pathway. Does this imply that the I-cell patient will present with Niemann-Pick symptoms Can I-cell disease be viewed as a constellation of many lysosomal storage diseases ... 

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. 

Schuchman, E. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inher Metabol Dis 30 (2007) 654-663. 

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

Niemann-Pick disease is an autosomal recessive disorder in which patients accumulate sphingomyelin and, to a lesser extenL cholesterol and other phospholipids within lyso-somes due to a deficiency of acid sphingomyelinase deficiency. While the monocyte/macrophage cell lineage is extensively affected, it is the accumulation within other cell... 

Takahashi, T, Desnick, RJ, Takada, G and Schnchman, EH (1992) Identification of a missense mntation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease. Hum Mutat, 1, 70-71. 

These are lipids containing a fatty acid, phosphoric acid, choline and the amino alcohol, sphingosine. They are deposited in the tissues in Niemann-Pick disease, a disorder of lipid storage. In some forms of this disease, a deficiency of the lysosomal enzyme, sphingomyelinase, can be demonstrated. 

Otterbach, B., and Stoffel, W., 1995, Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick). Cell 81 1053-1061. 

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