Niemann: Pick's Disease

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Niemann: Pick's Disease

Niemann Pick disease consists of a group of genetic disorders in which the common feature is a varying degree of sphingomyelin storage in certain tissues of the body. According to the current classification based on the enzymatic defect underlying these disorders, two main groups are distinguished. The first group, which comprises type A, which is characterized by a severe deficiency in acid sphingomyelinase activity, includes infantile neuronopathic form; and type B, an adult chronic form without neurologic symptoms. In the second heterogeneous group called type C, neuro-visceral involvement is massive and lipid metabolism is affected.

The sphingomyelin that accumulates in the lysosomes of the Niemann-Pick disease cells is thought to arise from the degradation of cells and their organelles since it is a major component of all mammalian cell membranes, the myelin sheath and the erythrocyte stroma. In Niemann-Pick type C, the main lipid accumulated in patients cells is not sphingomyelin but cholesterol, however, there is a close relationship between sphingomyelin metabolism and cholesterol metabolism.

Sphingomyelinase is an acidic lysosomal hydrolase that catalyses the cleavage of sphingomyelin to phosphoryl choline and ceramide. In patients with Pick’s disease its activity is deficient in all lysosome containing tissues. Patients with type A, the infantile form have 0.7% of the normal sphingomyelinase activity with median values in the range of 0-1% , while in patients with adult onset neuronopathic or non-neuronopathic disease the activity range is 0-19% of the normal, with median values in several tissues from 2-8% . This enzyme defect explains the massive deposition of sphingomyelin in tiss...

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...sh Medical Journal: 295(6610):1375-1376.

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