Interpretive Handbook

Test 61116 :
Niemann-Pick Disease, Types A and B, Known Mutation

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Niemann-Pick disease (types A and B) is an autosomal recessive lysosomal storage disease caused by a deficiency of the enzyme acid sphingomyelinase. The clinical presentation of type A disease is characterized by jaundice, progressive loss of motor skills, feeding difficulties, learning disabilities, and hepatosplenomegaly. Death usually occurs by age 3. Type B disease is generally milder, though variable in its clinical presentation. Most type B patients do not have neurologic involvement and survive to adulthood.


Mutations in the SMPD1 gene are responsible for the clinical manifestations of Niemann-Pick disease types A and B. Although this disease is panethnic, it has a significantly higher frequency in individuals of Ashkenazi Jewish and Northern African descent. The carrier rate for type A in the Ashkenazi Jewish population is 1/90. There are 3 common mutations in the Ashkenazi Jewish population: L302P, R496L, and fsP330, which account for approximately 97% of mutant alleles in this population. The deltaR608 mutation accounts for approximately 90% of the type B mutant alleles in individuals from the Maghreb region of North Africa and 100% of the mutant alleles in Gran Canaria Island.


The recommended test for carrier screening is NPD / Niemann-Pick Disease, Types A and B, Mutation Analysis, which tests for 4 of the most common SMPD1 mutations. For diagnostic testing, SPHT / Sphingomyelinase, Fibroblasts or LDSBS / Lysosomal Disorders Screen, Blood Spot should be performed prior to molecular analyses. Known mutation analysis of the SMPD1 gene should be utilized to detect private mutations in individuals with a family history of rare SMPD1 alterations.

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnostic confirmation of Niemann-Pick disease type A or B when familial mutations have been previously identified


Carrier screening of at-risk individuals when a mutation in the SMPD1 gene has been identified in an affected family member

Interpretation Provides information to assist in interpretation of the test results

An interpretive report will be provided.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

The identification of a disease-causing mutation in an affected family member is necessary before predictive testing for other family members can be offered. If a familial mutation has not been previously identified, order NPDMS / Niemann-Pick Disease, Types A and B, Full Gene Analysis.


Analysis is performed for the familial mutations provided only. This assay does not rule out the presence of other mutations within this gene or within other genes that may be associated with metabolic disease.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Any error in the diagnosis or in the pedigree provided to us, including false-paternity, could lead to erroneous interpretation of results.


A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories for instructions for testing patients who have received a bone marrow transplant.

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.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Schuchman EH: The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. J Inherit Metab Dis 2007 Oct;30(5):654-663

2. McGovern MM, Schuchman EH: Acid sphingomyelinase deficiency. In GeneReviews (Internet). Edited by RA Pagon, TD Bird, CR Dolan, et al: University of Washington, Seattle. 1993-2006 Dec 07 (updated 2009 Jun 25)