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.

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 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.

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 mutations 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 (see 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 (LSM 509), and 7-ketocholesterol (7-KC) may be seen; however, individuals with cholestasis may also present with this finding. Molecular testing of NPC1 and NPC2 (see NPCZ / Niemann-Pick Type C Disease, Full Gene Analysis) is helpful for disease confirmation, but may reveal variants of unknown significance, heterozygosity or absence of mutations 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 <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 The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill. Accessed March 19, 2019. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62643647

2. Patterson M: Niemann-Pick Disease Type C. Updated 29 Aug 2019 In GeneReviews Edited by MP Adam, HH Ardinger, RA Pagon, et al. University of Washington, Seattle. Accessed March 19, 2019. Available at https://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;7(6):499-511

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

Special Instructions Library of PDFs including pertinent information and forms related to the test