Diagnosis of Niemann-Pick disease type C
This test is not useful for Niemann-Pick disease type C carrier detection.
This is a diagnostic test for Niemann-Pick type C.
Test Id | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
FIBR | Fibroblast Culture | Yes | Yes |
CRYOB | Cryopreserve for Biochem Studies | No | Yes |
When this test is ordered, a fibroblast culture
NIEM: Radiolabeled Lipid Extraction using Thin Layer Chromatography
FIBR: Cultivated from Biopsy as Monolayer
CRYOB: Fibroblast Subculture followed by Cryopreservation and Storage
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)
When this test is ordered, a fibroblast culture
Tissue
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.
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
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.
Tissue in formalin or fixative preservative | Reject |
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
Tissue | Varies (preferred) |
Diagnosis of Niemann-Pick disease type C
This test is not useful for Niemann-Pick disease type C carrier detection.
This is a diagnostic test for Niemann-Pick type C.
When this test is ordered, a fibroblast culture
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
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.
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.
No significant cautionary statements
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§ionid=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
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)
Varies
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.
82658-Niemann-Pick type C
88233-Fibroblast culture
88240-Cryopreservation for biochemical studies
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 |