Diagnosis of Niemann-Pick disease types A and B
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Diagnostic test for Niemann-Pick types A and B. Not recommended for carrier detection.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =2.85 nmol/min/mg protein
This enzyme is deficient in Niemann-Pick disease types A and B.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Online Mendelian Inheritance in Man (OMIM): entries 257200 and 607616
2. Gal AE, Brady RO, Hibbert SR, Pentchev PG: A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease. N Engl J Med 1975;293:632-636
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
4. Schuchman EH: The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. Int J Clin Pharmacol Ther 2009;47 Suppl 1:S48-57
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