Sign in →

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

Additional Tests

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

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 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.

Specimen Type

Tissue


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 [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient


Specimen Stability Information

Specimen Type Temperature Time
Tissue Varies

Reference Values

If the results indicate that the patient's cultured fibroblasts esterify cholesterol at a level that 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.

Day(s) and Time(s) Performed

Varies

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 U.S. 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 In Process
29746 Interpretation (NIEM) 59462-2
29748 Reviewed By No LOINC Needed

Clinical Information

Niemann-Pick disease type C (NPC)(1) is caused by a defect in cellular cholesterol trafficking that results in the progressive accumulation of unesterified cholesterol in late endosomes/lysosomes. NPC is considered a lipid storage disorder with variable age of onset (range: perinatal period to adulthood), and 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 diagnosis of NPC has traditionally relied on the demonstration of impaired cholesterol esterification and positive filipin staining in cultured fibroblasts. Since it has been shown that individuals with NPC also exhibit elevated levels of oxysterol cholestane-3 beta,5 alpha,6 beta-triol (COT), oxysterol testing in plasma (see OXNP / Oxysterols, Plasma) or dried blood spot (see OXYBS / Oxysterols, Blood Spots) is an effective, quick, and less invasive first-tier alternative to cholesterol esterification and filipin staining.

 

The incidence of NPC is approximately 1 in 120,000 to 150,000 live births. NPC is an autosomal recessive condition and is caused by mutations in either the NPC1 or NPC2 genes. About 95% of individuals with NPC have mutations in the NPC1 gene. Mutations may also be identified in the NPC2 gene; see NPCZ / Niemann-Pick Type C Disease, Full Gene Analysis.

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.

Clinical Reference

1. Niemann-Pick disease, type C1; NPC1. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill, 2014. Accessed April 07, 2017. Available at www.omim.org/entry/257220?search=257220&highlight=257220

2. Patterson M: Niemann-Pick Disease type C. Reviewed July 18, 2013. Available at www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=npc;

3. 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

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 Gen 2013;22(21):4349-4356

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;8:12

Analytic Time

70-80 days depending on rapidity of growth

Method Name

NIEM: Radiolabeled Lipid Extraction Using Thin Layer Chromatography

CRYOB: Fibroblast Subculture Followed by Cryopreservation and Storage

Forms

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 (T576) is available in Special Instructions.

2. Biochemical Genetics Patient Information (T602) in Special Instructions

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical