Biomaterial Database

The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. 2009

E H Schuchman

Department of Genetics & Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA. edward.schuchman@mssm.edu

Patients with Niemann-Pick disease (NPD) Types A and B have an inherited deficiency of acid sphingomyelinase (ASM) activity. The clinical spectrum of this disorder ranges from the infantile neurological form that results in death by 3 years of age (NPD Type A) to the non-neurological form that is compatible with survival into adulthood (NPD Type B). Intermediate cases have also been reported, and the disease is best thought of as a single entity with a spectrum of phenotypes. ASM deficiency is panethnic, but appears to be more frequent in individuals of Middle Eastern and North African descent. Current estimates of the disease incidence range from 0.5 to 1 per 100,000 births, although these approximations are thought to underestimate the true frequency of the disorder. The gene encoding ASM--SMPD1--has been studied extensively, and over 100 mutations in SMPD1 have been found to cause ASM-deficient NPD. Based on these findings, DNA-based carrier screening has been implemented in the Ashkenazi Jewish community. ASM-knockout mouse models also have been generated and used to investigate disease pathogenesis and treatment with stem cell transplantation, gene therapy and enzyme replacement therapy (ERT). Based on these studies, clinical trials of ERT are underway in patients with non-neurological ASM-deficient NPD.

UI	MeSH Term	Description	Entries
D009542	Niemann-Pick Diseases	A group of autosomal recessive disorders in which harmful quantities of lipids accumulate in the viscera and the central nervous system. They can be caused by deficiencies of enzyme activities (SPHINGOMYELIN PHOSPHODIESTERASE) or defects in intracellular transport, resulting in the accumulation of SPHINGOMYELINS and CHOLESTEROL. There are various subtypes based on their clinical and genetic differences.	ASM Deficiency,ASM-Deficient Niemann-Pick Disease,Acid Sphingomyelinase Deficiency,Acid Sphingomyelinase-deficient Niemann-Pick Disease,Niemann-Pick Disease,ASM Deficiencies,ASM Deficient Niemann Pick Disease,ASM-Deficient Niemann-Pick Diseases,Acid Sphingomyelinase deficient Niemann Pick Disease,Deficiencies, ASM,Deficiencies, Acid Sphingomyelinase,Deficiency, ASM,Deficiency, Acid Sphingomyelinase,Disease, ASM-Deficient Niemann-Pick,Diseases, ASM-Deficient Niemann-Pick,Niemann Pick Disease,Niemann Pick Diseases,Niemann-Pick Disease, ASM-Deficient,Niemann-Pick Diseases, ASM-Deficient,Sphingomyelinase Deficiencies, Acid,Sphingomyelinase Deficiency, Acid
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013108	Sphingomyelin Phosphodiesterase	An enzyme that catalyzes the hydrolysis of sphingomyelin to ceramide (N-acylsphingosine) plus choline phosphate. A defect in this enzyme leads to NIEMANN-PICK DISEASE. EC 3.1.4.12.	Sphingomyelin Cholinephosphohydrolase,Sphingomyelin Cleaving Enzyme,Sphingomyelinase,Sphingomyelinase C
D015316	Genetic Therapy	Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.	Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D056947	Enzyme Replacement Therapy	Therapeutic replacement or supplementation of defective or missing enzymes to alleviate the effects of enzyme deficiency (e.g., GLUCOSYLCERAMIDASE replacement for GAUCHER DISEASE).	Enzyme Replacement Therapies,Replacement Therapies, Enzyme,Replacement Therapy, Enzyme,Therapies, Enzyme Replacement,Therapy, Enzyme Replacement
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out