Normal Function
The SMPD1 gene provides instructions for making an enzyme called acid sphingomyelinase. This enzyme is found in lysosomes, which are small compartments in the cell that digest and recycle molecules. Acid sphingomyelinase is responsible for the conversion of a fat (lipid) called sphingomyelin into another type of lipid called ceramide. Sphingomyelin also binds (attaches) to a fat called cholesterol and helps to form other lipids that play roles in various cell processes. The formations of these lipids is critical for the normal structure and function of cells and tissues.
Health Conditions Related to Genetic Changes
Niemann-Pick disease
At least 175 mutations in the SMPD1 gene have been found to cause Niemann-Pick disease types A and B. These types of Niemann-Pick disease are characterized by a buildup of fat within cells that leads to lung disease and enlargement of the liver and spleen (hepatosplenomegaly). Type A is more severe and is characterized by severe neurological impairment in early childhood.
SMPD1 gene mutations that cause complete loss of enzyme function tend to cause Niemann-Pick disease type A. In the Ashkenazi (eastern and central European) Jewish population, three mutations are responsible for about 90 percent of all Niemann-Pick disease type A cases. Mutations that lead to the production of an enzyme that retains some activity often cause Niemann-Pick disease type B. A reduction in enzyme activity within cells allows sphingomyelin to accumulate in cells. The accumulation of this lipid causes cells to malfunction and eventually die. Over time, cell loss impairs function of tissues and organs including the brain, lungs, spleen, and liver in people with Niemann-Pick disease types A and B.
More About This Health ConditionOther Names for This Gene
- acid sphingomyelinase
- ASM
- ASM_HUMAN
- sphingomyelin phosphodiesterase 1, acid lysosomal
- sphingomyelin phosphodiesterase 1, acid lysosomal (acid sphingomyelinase)
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Hollak CE, de Sonnaville ES, Cassiman D, Linthorst GE, Groener JE, Morava E, Wevers RA, Mannens M, Aerts JM, Meersseman W, Akkerman E, Niezen-Koning KE, Mulder MF, Visser G, Wijburg FA, Lefeber D, Poorthuis BJ. Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients. Mol Genet Metab. 2012 Nov;107(3):526-33. doi: 10.1016/j.ymgme.2012.06.015. Epub 2012 Jun 30. Citation on PubMed
- Irun P, Mallen M, Dominguez C, Rodriguez-Sureda V, Alvarez-Sala LA, Arslan N, Bermejo N, Guerrero C, Perez de Soto I, Villalon L, Giraldo P, Pocovi M. Identification of seven novel SMPD1 mutations causing Niemann-Pick disease types A and B. Clin Genet. 2013 Oct;84(4):356-61. doi: 10.1111/cge.12076. Epub 2013 Jan 4. Citation on PubMed
- Schuchman EH. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis. 2007 Oct;30(5):654-63. doi: 10.1007/s10545-007-0632-9. Epub 2007 Jul 12. Citation on PubMed
- Simonaro CM, Desnick RJ, McGovern MM, Wasserstein MP, Schuchman EH. The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations. Am J Hum Genet. 2002 Dec;71(6):1413-9. doi: 10.1086/345074. Epub 2002 Oct 4. Citation on PubMed or Free article on PubMed Central
- Wasserstein MP, Aron A, Brodie SE, Simonaro C, Desnick RJ, McGovern MM. Acid sphingomyelinase deficiency: prevalence and characterization of an intermediate phenotype of Niemann-Pick disease. J Pediatr. 2006 Oct;149(4):554-9. doi: 10.1016/j.jpeds.2006.06.034. Citation on PubMed
- Wasserstein MP, Desnick RJ, Schuchman EH, Hossain S, Wallenstein S, Lamm C, McGovern MM. The natural history of type B Niemann-Pick disease: results from a 10-year longitudinal study. Pediatrics. 2004 Dec;114(6):e672-7. doi: 10.1542/peds.2004-0887. Epub 2004 Nov 15. Citation on PubMed
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