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Test ID: NIEM Niemann-Pick Type C Detection, Fibroblasts

Reporting Name

Niemann-Pick Type C, Fibro

Useful For

Diagnosis of Niemann-Pick disease type C

 

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

Clinical Information

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

Interpretation

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.

Testing Algorithm

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.

Report Available

70 to 80 days

Day(s) Performed

Varies

Clinical Reference

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

Method Name

NIEM: Radiolabeled Lipid Extraction using Thin Layer Chromatography

FIBR: Cultivated from Biopsy as Monolayer

CRYOB: Fibroblast Subculture followed by Cryopreservation and Storage

Specimen Type

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


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


Specimen Stability Information

Specimen Type Temperature Time Special Container
Tissue Varies

Reference Values

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.

Test 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 US Food and Drug Administration.

CPT Code Information

82658-Niemann-Pick type C detection

88233-Fibroblast culture

88240-Cryopreservation for biochemical studies

LOINC Code Information

Test ID Test Order Name Order LOINC Value
NIEM Niemann-Pick Type C, Fibro In Process

 

Result ID Test Result Name Result LOINC Value
30173 Cholesterol Esterification 99061-4
29746 Interpretation (NIEM) 59462-2
29748 Reviewed By 18771-6

Additional Tests

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

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.

Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Behavioral, mml-Movement-Disorders, mml-Pediatric, mml-Neurometabolic, mml-Neuro-ophthalmology