Test Catalog

Test Id : NIEM

Niemann-Pick Type C Detection, Fibroblasts

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

Diagnosis of Niemann-Pick disease type C

 

This test is not useful for Niemann-Pick disease type C carrier detection.

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

This is a diagnostic test for Niemann-Pick type C.

Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.

Test Id Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes Yes
CRYOB Cryopreserve for Biochem Studies No Yes

Testing Algorithm
Delineates situations 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 one 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
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

NIEM: Radiolabeled Lipid Extraction using Thin Layer Chromatography

FIBR: Cultivated from Biopsy as Monolayer

CRYOB: Fibroblast Subculture followed by Cryopreservation and Storage

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

Niemann-Pick Type C, Fibro

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

Acyl-CoA:Cholesterol Acetyltransferase Assay

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)

Testing Algorithm
Delineates situations 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 one culture is required regardless of the number of enzyme assays ordered. If viable cells are not obtained within 10 days, client will be notified.

Specimen Type
Describes the specimen type validated for testing

Tissue

Ordering Guidance

This test is recommended only after appropriate analyte testing of oxysterols. For more information see OXNP / Oxysterols, Plasma; OXYBS / Oxysterols, Blood Spot; or OXYWB / Oxysterols, Blood.

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

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

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).

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:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Biochemical Genetics Patient Information (T602)

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

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

Tissue in formalin or fixative preservative Reject

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
Tissue Varies (preferred)

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

Diagnosis of Niemann-Pick disease type C

 

This test is not useful for Niemann-Pick disease type C carrier detection.

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

This is a diagnostic test for Niemann-Pick type C.

Testing Algorithm
Delineates situations 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 one culture is required regardless of the number of enzyme assays ordered. If viable cells are not obtained within 10 days, client will be notified.

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 lipid storage disorder resulting from variants in either the NPC1 (95% of cases) or NPC2 genes. Impaired cellular cholesterol trafficking results in progressive accumulation of unesterified cholesterol in late endosomes/lysosomes. NPC has a variable age of onset (range: perinatal period to adulthood) and a highly variable clinical presentation. Most individuals are diagnosed during childhood with symptoms that include ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, and seizures. Infants may present with or without hepatosplenomegaly and respiratory failure. Those without liver and pulmonary disease may present with hypotonia and developmental delay. Adult-onset NPC is associated with a slower progression and is characterized by psychiatric illness, ataxia, dystonia, and speech difficulties. The incidence of NPC is approximately 1 in 120,000 to 150,000 live births.

 

Measurement of oxysterols (products of cholesterol oxidation) are an effective, quick, and less invasive option for screening in an individual with suspected NPC (OXNP / Oxysterols, Plasma; OXYBS / Oxysterols, Blood Spot; OXYWB / Oxysterols, Blood). Elevated levels of cholestane-3-beta, 5-alpha, 6-beta-triol (COT), lyso-sphingomyelin 509, and 7-ketocholesterol may be seen; however, individuals with cholestasis may also present with this finding. Molecular testing of NPC1 and NPC2 (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specify NPC1 and NPC2 Gene List ID: IEMCP-H683JG) is helpful for disease confirmation but may reveal variants of unknown significance, heterozygosity, or absence of genetic variants in a patient with presumed NPC. Demonstration of impaired cholesterol esterification and positive filipin staining in cultured fibroblasts can be used to assess the functional significance of NPC1 or NPC2 variants and is helpful for disease confirmation in cases with a high clinical suspicion of NPC with ambiguous oxysterol results or cases where molecular testing is not informative

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 that is below 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 below 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

No significant cautionary statements

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

1. Patterson MC, Vanier MT, Suzuki K, et al Niemann-Pick disease type C: A lipid trafficking disorder. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed June 03, 2021. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225545907

2. Patterson M: Niemann-Pick disease type C. In: Adam MP, Ardinger HH, Pagon RA, et al: eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 10, 2020. Accessed June 03, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1296/

3. Patterson MC, Clayton P, Gissen P, et al: Recommendations for the detection and diagnosis of Niemann-Pick disease type C: An update. Neurol Clin Pract. 2017 Dec;7(6):499-511. doi: 10.1212/CPJ.0000000000000399

4. Bauer P, Balding DJ, Klunemann HH, et al: Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study. Hum Mol Genet. 2013 Nov;22(21):4349-4356. doi: 10.1093/hmg/ddt284

5. Patterson MC, Mengel E, Wijburg FA, et al: Disease and patient characteristics in NP-C patients: findings from an international disease registry. Orphanet J Rare Dis. 2013 Jan;8:12. doi: 10.1186/1750-1172-8-12

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

The formation of (3)H-cholesterol oleate is measured against cells that are fed only (3)H-oleic acid without low-density lipoprotein. 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; Cowan T, Pasquali M: Laboratory investigations of inborn errors of metabolism. In: Sarafoglou K, Hoffman GF, Roth KS, eds: Pediatric Endocrinology and Inborn Errors of Metabolism. 2nd ed. McGraw-Hill; 2017:1139-1158)

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.

70 to 80 days

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

3 years - Check with the lab for availability

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.

82658-Niemann-Pick type C detection

88233-Fibroblast culture

88240-Cryopreservation for biochemical studies

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
NIEM Niemann-Pick Type C, Fibro In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
30173 Cholesterol Esterification 99061-4
29746 Interpretation (NIEM) 59462-2
29748 Reviewed By 18771-6

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.

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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