Test Catalog

Test Id : NPCZ

Niemann-Pick Type C Disease, Full Gene Analysis, Varies

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

Second-tier test for confirming a biochemical diagnosis of Niemann-Pick type C (NPC)

 

Carrier testing of individuals with a family history of NPC in cases when an affected individual is not available for testing or disease-causing variants have not been identified

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing includes full gene sequencing of the NPC1 and NPC2 genes, including analysis for large deletions and duplications.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

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

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If a skin biopsy is received, fibroblast culture will be performed at an additional charge.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR) followed by DNA Sequencing/ Multiplex Ligation-Dependent Probe Amplification (MLPA)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

NPC1/NPC2 Genes, Full Gene Analysis

Aliases
Lists additional common names for a test, as an aid in searching

N-P

Niemann

Niemann-Pick Disease (NPD)

Niemann-Pick Type C (NPC)

NPC1

NPC2

NPD (Niemann-Pick Disease)

NPCMS

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If a skin biopsy is received, fibroblast culture will be performed at an additional charge.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

First-tier testing to screen for Niemann-Pick type C disease is available. Order OXNP / Oxysterols, Plasma.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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:

 

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

 

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

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

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

Second-tier test for confirming a biochemical diagnosis of Niemann-Pick type C (NPC)

 

Carrier testing of individuals with a family history of NPC in cases when an affected individual is not available for testing or disease-causing variants have not been identified

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

Testing includes full gene sequencing of the NPC1 and NPC2 genes, including analysis for large deletions and duplications.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If a skin biopsy is received, fibroblast culture will be performed at an additional charge.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Niemann-Pick type C (NPC) is an inherited disorder of cholesterol transport that results in an accumulation of unesterified cholesterol and lipids in the lysosomal/endosomal system and in various tissues. Although NPC belongs to a group of lysosomal disorders including Niemann-Pick types A and B, these diseases are metabolically and genetically distinct. Niemann-Pick types A and B are caused by variant in the SMPD1 gene, which encodes the enzyme sphingomyelinase, whereas NPC is caused by variants in the NPC1 or NPC2 genes.

 

The incidence of NPC is approximately 1 in 120,000 to 1 in 150,000 live births. Age of onset is variable and ranges from the perinatal period to adulthood. Clinical presentation is also highly variable. Infants may present with or without liver disease (hepatosplenomegaly) and respiratory failure. Those without liver and pulmonary disease may present with hypotonia and developmental delay. Most individuals are diagnosed during childhood with symptoms including ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, and seizures resulting in death by the second or third decade of life. Adult-onset NPC is associated with a slower progression and is characterized by neurologic and psychiatric problems.

 

NPC is inherited in an autosomal recessive manner, in which affected individuals carry 2 variants in either the NPC1 or NPC2 gene. Most variants are family specific, although there are 2 variants in the NPC1 gene that are more common than others. The G992W alteration is common in the French Acadian population of Nova Scotia. The I1061T alteration is the most common variant worldwide, and is seen in patients of Hispanic and Western European (United Kingdom and France) descent. Full gene sequencing and analysis for large deletions and duplications of the NPC1 and NPC2 genes detect less common disease-causing variants. 

 

The recommended first-tier test to screen for NPC is a biochemical test measuring oxysterols (OXNP / Oxysterols, Plasma). Molecular testing provides confirmation of a biochemical diagnosis or a basis for carrier testing of family members. Individuals with abnormal biochemical results are more likely to have 2 identifiable variants by molecular testing. Additionally, cholesterol esterification coupled with filipin staining on a fibroblast specimen (NIEM / Niemann-Pick Type C Detection, Fibroblasts) can aid in diagnosis.

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.

Interpretation
Provides information to assist in interpretation of the test results

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.

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 type C (NPC) disease may have a variant that is not identified by this method (eg, promoter alterations, deep intronic alterations). The absence of a variant, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of NPC. For carrier testing, it is important to first document the presence of NPC1 or NPC2 gene variants in an affected family member.

 

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.

 

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.

 

In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

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. NP-C Guidelines Working Group, Wraith JE, Baumgartner MR, et al: Recommendations on the diagnosis and management of Niemann-Pick disease type C. Mol Genet Metab. 2009 Sep-Oct;98(1-2):152-65

3. Park WD, O'Brien JF, Lundquist PA, et al: Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1. Hum Mutat. 2003 Oct;22(4):313-325

4. Vanier MT: Niemann-Pick disease type C. Orphanet J Rare Dis. 2010 Jun 3;5:16

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Bidirectional sequence analysis is performed to test for the presence of a variant in all coding regions and intron/exon boundaries of the NPC1 gene and NPC2 gene. Gene dosage analysis by multiplex ligation-dependent probe amplification (MLPA) is used to test for the presence of large deletions and duplications within these genes.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

14 to 20 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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 US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81404-NPC2 (Niemann-Pick disease, type C2 [epididymal secretory protein E1]) (eg, Niemann-Pick disease type C2), full gene sequence

81406-NPC1 (Niemann-Pick disease, type C1) (eg, Niemann-Pick disease), full gene sequence

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

88240-Cryopreservation (if appropriate)

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports