Interpretive Handbook

Test 85322 :
Niemann-Pick Disease, Types A and B, Mutation 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 a 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 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 known to cause Niemann-Pick disease types A and B. The carrier rate for Niemann-pick type A in the Ashkenazi Jewish population is 1/90. There are 3 common mutations in the Ashkenazi Jewish population: L302P, R496L, and fsP330. The carrier detection rate for Niemann-Pick type A with these 3 mutations using this assay is approximately 97%. 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 mutation alleles in Gran Canaria Island.

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

Carrier testing for individuals of Ashkenazi Jewish ancestry


Prenatal diagnosis for at-risk pregnancies


Confirmation of suspected clinical diagnosis of Niemann-Pick disease types A and B in individuals of Ashkenazi Jewish ancestry

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

This assay will not detect all of the mutations that cause Niemann-Pick disease types A and B. Therefore, the absence of a detectable mutation does not rule out the possibility that an individual is a carrier of or affected with this disease.


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.


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.


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


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. Gross SJ, Pletcher BA, Monaghan KG: Carrier screening in individuals of Ashkenazi Jewish descent. Genet Med 2008 Jan;10(1):54-56

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