Interpretive Handbook

Test 61117 :
Niemann-Pick Disease, Types A and B, Full Gene Analysis

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.


Targeted mutation analysis (NPD / Niemann-Pick Disease, Types A and B, Mutation Analysis) for these 4 mutations is thought to detect 90% of the mutant alleles leading to acid sphingomyelinase deficiency. Full gene analysis of the SMPD1 gene should be utilized to detect private mutations in individuals with abnormal enzyme activity and 1 or no mutations detected by the panel of common mutations (NPD).


NPD / Niemann-Pick Disease, Types A and B, Mutation Analysis is also the recommended test for carrier screening. For diagnostic testing, SPHT / Sphingomyelinase, Fibroblasts or LDSBS / Lysosomal Disorders Screen, Blood Spot should be performed prior to targeted mutation analysis or full gene analysis.

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

Confirmation of a diagnosis of Niemann-Pick disease type A or B 

Carrier screening in cases where there is a family history of Niemann-Pick disease type A or B, but disease-causing mutations have not been identified in an affected individual

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

A small percentage of individuals who are carriers or have a diagnosis of Niemann-Pick disease type A or B may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of Niemann-Pick disease type A or B. For carrier testing, it is important to first document the presence of an SMPD1 gene mutation in an affected family member; however, when no mutations are detected by NPD / Niemann-Pick Disease, Types A and B, Mutation Analysis, this test (NPDMS) should be ordered.


In some cases, DNA alterations of undetermined significance may be identified.


Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.


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.


Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

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 June 25)