title: Types A and B Niemann-Pick disease.
abstract: Two distinct metabolic abnormalities are encompassed under the eponym Niemann-Pick disease (NPD). The first is due to the deficient activity of the enzyme acid sphingomyelinase (ASM). Patients with ASM deficiency are classified as having types A and B Niemann-Pick disease (NPD). Type A NPD patients exhibit hepatosplenomegaly in infancy and profound central nervous system involvement. They rarely survive beyond two years of age. Type B patients also have hepatosplenomegaly and pathologic alterations of their lungs, but there are usually no central nervous system signs. The age of onset and rate of disease progression varies greatly among type B patients, and they frequently live into adulthood. Recently, patients with phenotypes intermediate between types A and B NPD also have been identified. These individuals represent the expected continuum caused by inheriting different mutations in the ASM gene (SMPD1). Patients in the second NPD category are designated as having types C and D NPD. These patients may have mild hepatosplenomegaly, but the central nervous system is profoundly affected. Impaired intracellular trafficking of cholesterol causes types C and D NPD, and two distinct gene defects have been found. In this chapter only types A and B NPD will be discussed.
authors.affiliation: Department of Genetics & Genomic Sciences, Ichan School of Medicine at Mount Sinai, 1425 Madison Avenue, Room 14-20A, New York, NY 10029, United States. Electronic address: edward.schuchman@mssm.edu.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
authors.affiliation: Department of Genetics & Genomic Sciences, Ichan School of Medicine at Mount Sinai, 1428 Madison Avenue, 1st Floor, Room AB1-12, New York, NY 10029, United States. Electronic address: melissa.wasserstein@mssm.edu.
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Wasserstein
mesh_terms: D016026:Bone Marrow Transplantation; D002493:Central Nervous System Diseases / Q000209:etiology*; D056947:Enzyme Replacement Therapy; D006529:Hepatomegaly / Q000209:etiology*; D006801:Humans; D008171:Lung Diseases / Q000209:etiology*; D052536:Niemann-Pick Disease, Type A / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D052537:Niemann-Pick Disease, Type B / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D010641:Phenotype; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics; D013163:Splenomegaly / Q000209:etiology*
chemical_list: D013108:Sphingomyelin Phosphodiesterase
keywords: Niemann-Pick; acid Sphingomyelinase; enzyme replacement therapy; mouse model; sphingomyelin