Niemann-Pick disease is a progressively debilitating, neurogenetic disorder which is characterized biochemically by the accumulation of sphingomelin in several tissues and organs in conjunction with deficiency of the lysosomal hydrolase, sphingomyelinase. Detailed description of various phenotypes in terms of cellular pathochemistry and molecular genetics has not been accomplished to date. A major obstacle in this area has been the absence of reproducible techniques for the isolation of homogeneous preparations of sphingomyelinas. Employing novel detergent and chromatography systems, we have purified sphingomyelinase to homogeneity. The purified enzyme migrates with an apparent molecular weight of 67,000 daltons in SDS-polyacrylamide gels under both reducing and nonreducing conditions. Kinetic analyses and determinations of the primary protein structure and carbohydrate composition are in progress. Polyclonal antibodies have been raised to the purified enzyme that will assert incloning the gene for sphingomyelinase. Characterization of the phenotypes of Niemann-Pick disease in terms of protein polymorphisms and specific mutations at the DNA level will be undertaken.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Research (Z01)
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