Test ID NPABP Niemann-Pick Disease, Types A and B, Mutation Analysis

Useful For

Carrier testing of Niemann-Pick disease types A and B for individuals of Ashkenazi Jewish ancestry

Prenatal diagnosis of Niemann-Pick disease types A and B for at-risk pregnancies

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

Reflex Tests

Test ID	Reporting Name	Available Separately	Always Performed
CULFB	Fibroblast Culture for Genetic Test	Yes	No
CULAF	Amniotic Fluid Culture/Genetic Test	Yes	No
MATCC	Maternal Cell Contamination, B	Yes	No

Testing Algorithm

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture/genetic test will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal sample that is received, maternal cell contamination studies will be added.

Special Instructions

Method Name

Polymerase Chain Reaction (PCR) Analysis (PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)

Reporting Name

Niemann-Pick Disease, Types A and B

Specimen Type

Varies

Forms:

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

Specimen preferred to arrive within 96 hours of collection.

Submit only 1 of the following specimens:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 2.6 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated/Frozen

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. CST on Friday in order to be processed appropriately. All prenatal specimens must be accompanied by a maternal blood specimen. Order MATCC / Maternal Cell Contamination, Molecular Analysis on the maternal specimen.

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Specimen Minimum Volume

Blood: 0.5 mL/Amniotic Fluid: 10 mL/Chorionic Villi: 5 mg

Specimen Stability Information

Specimen Type	Temperature	Time
Varies	Varies

Clinical Information

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 in 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.

Reference Values

An interpretive report will be provided.

Cautions

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.

Day(s) Performed

Tuesday; 10 a.m.

Report Available

3 days

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81330-SMPD1 (Sphingomyelin phosphodiesterase 1, acid lysosomal) (eg, Niemann-Pick disease, Type A) gene analysis, common variants (eg, R496L, L302P, fsP330)

Fibroblast Culture for Genetic Test

88233-Tissue culture, skin or solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

Amniotic Fluid Culture/Genetic Test

88235-Tissue culture for amniotic fluid (if appropriate)