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Niemann-Pick types A and B (NPA and NPB) are caused by a deficiency of sphingomyelinase, which results in extensive storage of sphingomyelin and cholesterol in the liver, spleen, lungs, and, to a lesser degree, brain. Classification of individuals as having type A or type B is based on age of onset as well as the severity of symptoms. NPA disease is more severe than NPB and characterized by early onset with feeding problems, dystrophy, persistent jaundice, cherry red maculae, development of hepatosplenomegaly, neurological deterioration, deafness, and blindness, leading to death by age 3. NPB disease is limited to visceral symptoms with survival into adulthood. Some patients have been described with intermediary phenotypes. Characteristic of the disease are large lipid-laden foam cells on bone marrow biopsy.The combined prevalence of NPA and NPB is estimated to be 1 in 250,000. NPA and NPB are inherited in an autosomal recessive manner and are caused by mutations in the SMPD1 gene. Although there is a higher frequency of type A among the Ashkenazi Jewish population, both types are pan-ethnic. Molecular genetic testing for NPA and NPB disease is also available (see NPDMS / Niemann-Pick Disease, Types A and B, Full Gene Analysis).
Diagnosis of Niemann-Pick disease types A and B
This enzyme is deficient in Niemann-Pick disease types A and B.
Interfering factors include:
-Lack of viable cells or bacterial contamination
-Failure to transport tissue in an appropriate media
-Excessive transport time
-Exposure of the specimen to temperature extremes (freezing or >30 degrees C)
This test is not useful for Niemann-Pick type C detection (see NIEM / Niemann-Pick Type C Detection, Fibroblasts).
Level of residual enzyme activity is not a reliable indicator or predictor of severity.
> or =2.85 nmol/min/mg protein
1. Online Mendelian Inheritance in Man (OMIM): entries 257200 and 607616
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3. McGovern MM, Schuchman EH: Acid Sphingomyelinase Deficiency. In GeneReviews. Edited by RA Pagon, MP Adam, TD Bird, et al. Last update June 25, 2009. Available from URL: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=npab
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5. Hollack CE, de Sonnaville ES, Cassiman D, et al: Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: Disease spectrum and natural course in attenuated patients. Mol Gen Metab 2012;107:526-533