Test ID: NIEM
Niemann-Pick Type C Detection, Fibroblasts
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
Detection of a unique form of type C Niemann-Pick disease
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Diagnostic test for Niemann-Pick Type C. Not recommended for carrier detection. Cholesterol esterification followed by filipin staining, if positive.
Additional Tests Lists test(s) that are always performed, at an additional charge, with the initial test(s)
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| FIBR | Fibroblast Culture | Yes | Yes |
| CRYOB | Cryopreserve for Biochem Studies | No | Yes |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, a fibroblast culture and cryopreservation for biochemical studies will always be performed at an additional charge. However, for multiple lysosomal enzyme assays on a patient utilizing fibroblast culture, only 1 culture is required regardless of the number of enzyme assays ordered. If viable cells are not obtained within 10 days, client will be notified.
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
Method Name A short description of the method used to perform the test
NIEM/9313: Radiolabeled Lipid Extraction Using Thin Layer Chromatography
CRYOB/88832: Fibroblast Subculture Followed by Cryopreservation and Storage
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
Cholesterol Esterification Assay
Filipin Staining
Niemann Pick IIA
Niemann Pick Type IIA
Niemann-Pick Disease (NPD) Type C
Niemann-Pick IIA
Niemann-Pick Type C (NPC)
Niemann-Pick Type IIA
NPC (Niemann-Pick Type C)
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.
This test is not recommended for prenatal testing.
Forms:
1. 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. 2. If not ordering electronically, submit a Biochemical Genetics Request Form (Supply T439) with the specimen.
Submit only 1 of the following specimens:
Specimen Type: Cultured fibroblasts
Container/Tube: T-75 or T-25 flask
Specimen Volume: 1 full T-75 flask 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.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | NA |
| Lipemia | NA |
| Icterus | NA |
| Other | Specimen in formalin or fixative preservative |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Tissue | Varies | |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal storage disorder caused by a defect in cellular cholesterol trafficking due to mutations in either the NPC1 or NPC2 gene. The resulting accumulation of unesterified cholesterol in late endosomes/lysosomes interrupts the normal functioning of cells, tissues, and organs. There are 2 other forms of Niemann-Pick disease, types A and B, resulting from a deficiency of sphingomyelinase and mutations in the SMPD1 gene.
Clinical features of NPC vary widely depending on the age of onset, which can range from the neonatal period to adulthood. Most cases present in middle to late childhood with a classic disease course. Hepatosplenomegaly may be the initial symptom of the disease. Clinical manifestations include vertical gaze palsy, ataxia, dystonia, behavioral problems, and dementia. In early onset cases, severe, lethal neonatal liver disease and hydrops fetalis can occur. Common features of adult onset NPC include psychiatric illness, ataxia, dystonia, and speech difficulties. Currently, treatment and management are supportive only.
Biochemical testing that demonstrates impaired cholesterol esterification and positive filipin staining in cultured fibroblasts is diagnostic for NPC. About 90% of individuals with NPC have mutations in the NPC1 gene. Mutations may also be identified in the NPC2 gene; see NPCMS/89015 Niemann-Pick Type C, Full Gene Analysis.
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.
If the results indicate that the patient's cultured fibroblasts esterify cholesterol at a level which is <10% of normal cultured fibroblasts and when filipin staining shows excessive storage of free cholesterol, it will be stated that the patient is positive for Niemann-Pick type C disease. All samples will be stained by filipin to see if a milder biochemical phenotype is the likely cause of the Niemann-Pick disease-like clinical picture.
Interpretation Provides information to assist in interpretation of the test results
Values expected in Niemann-Pick disease type C are <10% of that found in normal cultured fibroblasts.
Values between 10% and 80% of normal will have to be judged on other diagnostic criteria.
All values will be followed up by filipin staining for cholesterol.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Biochemical testing is unreliable for Niemann-Pick disease type C carrier detection.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Kruth HS, Comly ME, Butler JD, et al: Type C Niemann-Pick disease: abnormal metabolism of low density lipoprotein in homozygous and heterozygous fibroblasts. J Biol Chem 1986;261:16769-16774
2. Pentchev PG, Kruth HS, Comley ME, et al: Type C Niemann-Pick disease: a parallel loss of regulatory responses in both the uptake and esterification of low density lipoprotein-derived cholesterol in cultured fibroblasts. J Biol Chem 1986;261:16775-16780
3. Patterson M: Niemann-Pick Disease type C. Available from: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=npc Reviewed July 22, 2008
4. Enns GM, Steiner RD, Cowan TM: Lysosomal Disorders. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth, New York, McGraw-Hill Medical Division, 2009, pp 740
Method Description Describes how the test is performed and provides a method-specific reference
The formation of (3)H-cholesterol oleate is measured against cells which are fed only (3)H-oleic acid without LDL. The formed (3)H-cholesterol oleate is separated from (3)H-oleic acid and its other esterified forms by thin-layer chromatography (TLC). The areas on the TLC plates corresponding to the cholesterol oleate markers are then scraped and counted on a liquid scintillation counter. Lowry proteins are done on the cell pellet to normalize the assay roughly to cell numbers. Filipin staining for cholesterol is performed on all specimens with low values.(Kruth HS, Comly ME, Butler JD, et al: Type C Niemann-Pick disease: abnormal metabolism of low density lipoprotein in homozygous and heterozygous fibroblasts. J Biol Chem 1986;261:16769-16774; Pentchev PG, Kruth HS, Comley ME, et al: Type C Niemann-Pick disease: a parallel loss of regulatory responses in both the uptake and esterification of low density lipoprotein-derived cholesterol in cultured fibroblasts. J Biol Chem 1986;261:16775-16780)
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.
Varies
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
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.
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.
82658-Niemann-Pick type C detection
88233-Fibroblast culture
88240-Cryopreservation for biochemical studies
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 |
|---|---|---|
| 29740 | Specimen | 31208-2 |
| 29741 | Specimen ID | N/A |
| 29742 | Source | N/A |
| 29743 | Order Date | N/A |
| 29744 | Reason For Referral | 42349-1 |
| 29745 | Method | In Process |
| 30173 | Cholesterol Esterification | In Process |
| 29746 | Interpretation | 59462-2 |
| 29747 | Amendment | In Process |
| 29748 | Reviewed By | N/A |
| 29749 | Release Date | N/A |
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