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

Useful For

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

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.

 

See Newborn Screen Follow-up for Niemann Pick Type A and B in Special Instructions.

Method Name

Polymerase Chain Reaction (PCR) Followed by DNA Sequence Analysis

Reporting Name

Niemann-Pick A-B Full Gene Analysis

Specimen Type

Varies


Advisory Information


PLSD / Lysosomal and Peroxisomal Storage Disorders Screen, Blood Spot and OXYBS / Oxysterols, Blood Spots or OXNP / Oxysterols, Plasma should be performed prior to targeted mutation analysis or full gene analysis.

 

NPABP / Niemann-Pick Disease, Types A and B, Mutation Analysis is the recommended test for carrier screening.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Submit only 1 of the following specimens:

 

Preferred

Specimen Type: Whole blood

Container/Tube:

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

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

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

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper, or Blood Spot Collection Card (T493)

Specimen Volume: 2 to 5 Blood Spots on collection card (Whatman Protein Saver 903 Paper; Ahlstrom 226 filter paper; or Blood Spot Collection Card, T493)

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated


Specimen Minimum Volume

Blood: 1 mL/Blood Spots: 5 punches-3 mm diameter

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Clinical Information

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 (NPABP / 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.

                                               

NPABP / Niemann-Pick Disease, Types A and B, Mutation Analysis is also the recommended test for carrier screening. For diagnostic testing, PLSD / Lysosomal and Peroxisomal Storage Disorders Screen, Blood Spot and OXYBS / Oxysterols, Blood Spots or OXNP / Oxysterols, Plasma, should be performed prior to targeted mutation analysis or full gene analysis.

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Reference

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

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

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

Day(s) and Time(s) Performed

Performed weekly, varies

Analytic Time

14 days

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

81479-Unlisted molecular pathology procedure

 

Fibroblast Culture for Genetic Test

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

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
NPABZ Niemann-Pick A-B Full Gene Analysis In Process

 

Result ID Test Result Name Result LOINC Value
53093 Result Summary 50397-9
53094 Result No LOINC Needed
53095 Interpretation 69047-9
53096 Additional Information 48767-8
53097 Specimen 31208-2
53098 Source 31208-2
53099 Released By No LOINC Needed

Forms

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

2. 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.

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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