Test ID NPABZ Niemann-Pick Disease, Types A and B, Full Gene Analysis, Varies
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 variants have not been identified in an affected individual
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
FIBR | Fibroblast Culture | Yes | No |
CRYOB | Cryopreserve for Biochem Studies | No | No |
Testing Algorithm
If a skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be performed at an additional charge.
See Newborn Screen Follow-up for Niemann Pick Type A and B in Special Instructions.
For more information, see Newborn Screening Act Sheet Niemann-Pick A/B Disease: Decreased Acid Sphingomyelinase in Special Instructions.
Special Instructions
- Molecular Genetics: Biochemical Disorders Patient Information
- Informed Consent for Genetic Testing
- Blood Spot Collection Card-Spanish Instructions
- Newborn Screening Act Sheet Niemann-Pick A/B Disease: Decreased Acid Sphingomyelinase
- Newborn Screen Follow-up for Niemann Pick Type A and B
- Blood Spot Collection Card-Chinese Instructions
- Informed Consent for Genetic Testing (Spanish)
- Blood Spot Collection Instructions
Method Name
Polymerase Chain Reaction (PCR) followed by DNA Sequencing
Reporting Name
Niemann-Pick A-B Full Gene AnalysisSpecimen Type
VariesAdvisory Information
Both ASMW / Acid Sphingomyelinase, Leukocytes and OXNP / Oxysterols, Plasma should be performed prior to targeted variant or full gene analyses.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
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.
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
Specimen Volume: 2 to 5 Blood Spots on collection card
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
Additional Information:
1. For collection instructions, see Blood Spot Collection Instructions in Special Instructions.
2. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.
3. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.
Specimen Minimum Volume
Blood: 1 mL
Blood Spots: 5 punches-3 mm diameter
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
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.
Variants 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 in 90 individuals. There are 3 common variants in the Ashkenazi Jewish population: L302P, R496L, and fsP330, which account for approximately 97% of variant alleles in this population. The deltaR608 alteration accounts for approximately 90% of the type B variant alleles in individuals from the Maghreb region of North Africa and 100% of the variant alleles in Gran Canaria Island.
For diagnostic testing, analysis of the acid sphingomyelinase enzyme (ASMW / Acid Sphingomyelinase, Leukocytes) and 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 and Genomics (ACMG) 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. Wasserstein MP, Schuchman EH: Acid sphingomyelinase deficiency. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet].University of Washington, Seattle; 2006. Updated June 18, 2015. Accessed July 1, 2020. Available at www.ncbi.nlm.nih.gov/books/NBK1370/
Day(s) and Time(s) Performed
Performed weekly; Varies
Analytic Time
14 daysTest 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
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 | 34518-1 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
53093 | Result Summary | 50397-9 |
53094 | Result | 82939-0 |
53095 | Interpretation | 69047-9 |
53096 | Additional Information | 48767-8 |
53097 | Specimen | 31208-2 |
53098 | Source | 31208-2 |
53099 | Released By | 18771-6 |
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions
3. If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen.