Niemann-Pick Type C, Full Gene Analysis
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Second-tier test for confirming a biochemical diagnosis of Niemann-Pick type C (NPC)
Carrier testing of individuals with a family history of NPC but an affected individual is not available for testing or disease-causing mutations have not been identified
Genetics Test Information Provides information that may help with selection of the correct 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 test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
|Test ID||Reporting Name||Available Separately||Always Performed|
|FBC||Fibroblast Culture for Genetic Test||Yes||No|
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
If skin biopsy is received, fibroblast culture for genetic test will be added and charged separately.
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Polymerase chain reaction (PCR) amplification followed by DNA sequencing is utilized to test for the presence of a mutation in the NPC1 and NPC2 genes and Gene Dosage Analysis by Multiplex Ligation-Dependent Probe Amplification (MLPA)
FBC/80333: Cell Culture
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
NPC Mutation Screen
Niemann-Pick Disease (NPD)
NPD (Niemann-Pick Disease)
Niemann-Pick Type C (NPC)
Niemann-Pick Disease (NPD)
NPD (Niemann-Pick Disease)
Niemann-Pick Type C (NPC)
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
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 (Supply T576) is available in Special Instructions.
2. Molecular Genetics-Biochemical Disorders Patient Information Sheet (Supply T527) in Special Instructions
3. If not ordering electronically, submit a Molecular Genetics Request Form (Supply T245) with the specimen.
Specimen must arrive within 96 hours of collection.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
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
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 [Supply T115]).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Blood: 1 mL
No specimen should be rejected. If specimen not received at appropriate temperature or in wrong anticoagulant, include note to laboratory. If questions, contact laboratory.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
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 mutations in the SMPD1 gene, which encodes the enzyme sphingomyelinase, whereas NPC is caused by mutations in the NPC1 or NPC2 genes.
The incidence of NPC is approximately 1:120,000 to 1:150,000 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 mutations in either the NPC1 or NPC2 gene. Most mutations are family specific, although there are 2 mutations in the NPC1 gene which are more common than others. The G992W mutation is common in the French Acadian population of Nova Scotia. The I1061T mutation is the most common mutation 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 mutations.
The recommended first-tier test to screen for NPC is a biochemical test measuring cholesterol esterification coupled with filipin staining on a fibroblast specimen, NIEM/9313 Niemann-Pick Type C Detection, Fibroblasts. 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 mutations by molecular testing.
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.
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
A small percentage of individuals who are carriers or have a diagnosis of, Niemann-Pick type C (NPC) disease may have a mutation that is not identified by this method (eg, promoter mutations, deep intronic alterations). The absence of a mutation(s), 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 mutations 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.
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.
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 Provides recommendations for further in-depth reading of a clinical nature
1. 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
2. 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
3. Vanier MT: Niemann-Pick disease type C. Orphanet J Rare Dis 2010 Jun 3;5:16
Method Description Describes how the test is performed and provides a method-specific reference
DNA sequencing is utilized to test for the presence of a mutation in all 25 exons of the NPC1 gene and 5 exons of the 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)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Thursday; 10 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
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 The location of the laboratory that performs the test
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's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) 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 U.S. 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 Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81479- Unlisted molecular pathology procedure
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|27475||Reason For Referral||42349-1|