Test Id : OXNP
Oxysterols, Plasma
Useful For
Suggests clinical disorders or settings where the test may be helpful
Investigating a possible diagnosis of Niemann-Pick disease types A, B, or C using plasma specimens
Monitoring of individuals with Niemann-Pick type C disease
This test is not useful for the identification of carriers.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For more information see Newborn Screen Follow-up for Acid Sphingomyelinase Deficiency
If the patient has abnormal newborn screening results for Niemann- Pick disease, refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1)
Method Name
A short description of the method used to perform the test
Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
Niemann-Pick type A
Niemann-Pick type B
Niemann-Pick type C
ASM Deficiency
Acid Sphingomyelinase Deficiency
ASMD
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For more information see Newborn Screen Follow-up for Acid Sphingomyelinase Deficiency
If the patient has abnormal newborn screening results for Niemann- Pick disease, refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1)
Specimen Type
Describes the specimen type validated for testing
Plasma
Ordering Guidance
This test is also available as a part of a panel; see HSMP / Hepatosplenomegaly Panel, Plasma. If this test (OXNP) is ordered with either GPSYP / Glucopsychosine, Plasma or CTXP / Cerebrotendinous Xanthomatosis, Plasma, the individual tests will be canceled and HSMP ordered.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Supplies: Sarstedt Aliquot Tube 5 mL (T914)
Collection Container/Tube:
Preferred: Lavender top (EDTA)
Acceptable: Green top (sodium heparin or lithium heparin), yellow top (ACD B)
Submission Container/Tube: Plastic vial
Specimen Volume: 0.3 mL
Collection Instructions:
1. Centrifuge at 4 degrees C.
2. Aliquot plasma into plastic vial. Do not disturb the buffy coat layer.
3. Send frozen.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
Forms
If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
0.25 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | OK |
| Gross lipemia | OK |
| Gross icterus | OK |
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 |
|---|---|---|---|
| Plasma | Frozen | 65 days |
Useful For
Suggests clinical disorders or settings where the test may be helpful
Investigating a possible diagnosis of Niemann-Pick disease types A, B, or C using plasma specimens
Monitoring of individuals with Niemann-Pick type C disease
This test is not useful for the identification of carriers.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For more information see Newborn Screen Follow-up for Acid Sphingomyelinase Deficiency
If the patient has abnormal newborn screening results for Niemann- Pick disease, refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1)
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Niemann-Pick disease types A, B, and C (NPA, NPB, and NPC, respectively) are a group of autosomal recessive lysosomal storage disorders affecting metabolism of specific lipids within cells.
Niemann-Pick disease types A and B, also known as acid sphingomyelinase deficiency, result in extensive storage of sphingomyelin and cholesterol in the liver, spleen, lungs, and may also affect the brain. NPA disease is more severe than NPB, and it is characterized by early onset with feeding problems, dystrophy, persistent jaundice, hepatosplenomegaly, neurological deterioration, deafness, and blindness leading to death by 3 years of age. NPB disease is limited to visceral symptoms, such as hepatosplenomegaly, with survival into adulthood. Some patients have been described with intermediary clinical phenotypes. Large, lipid-laden foam cells are characteristic of the disease. Approximately 50% of patients with this condition have cherry-red spots in the macula.
Treatment is available in the form of enzyme replacement therapy, which helps to reduce the accumulation of sphingomyelin; however, it is not effective in treating the central nervous system.
The combined prevalence of NPA and NPB is estimated to be 1 in 250,000 individuals. NPA and NPB are inherited in an autosomal recessive manner and are caused by biallelic disease-causing variants in the SMPD1 gene. Although there is a higher frequency of type A among the Ashkenazi Jewish population, both types are panethnic. Individuals with NPA and NPB typically have elevations of lyso-sphingomyelin (LSM) and LSM 509 combined with potential elevations in cholestane-3 beta, 5 alpha, 6 beta-triol (COT) or 7-ketocholesterol (7-KC). Molecular genetic testing for NPA and NPB disease is also available (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specify gene list ID: IEMCP-W6S9XD).
Niemann-Pick disease type C is caused by a defect in cellular cholesterol trafficking, which results in the progressive accumulation of unesterified cholesterol in late endosomes/lysosomes. NPC is considered a lipid storage disorder with variable age of onset, from neonates 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.
New treatments are available for patients with NPC that help improve both the neurological and functional symptoms.
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 biallelic disease-causing variants in either the NPC1 or NPC2 genes. Individuals with NPC exhibit elevated levels of oxysterol COT; LSM 509 and7-KC may also be elevated. The diagnosis of NPC can be confirmed by demonstration of impaired cholesterol esterification and positive filipin staining in cultured fibroblasts. For molecular confirmation, genetic testing for NPC disease can be performed (CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies; specify gene list ID: IEMCP-H683JG).
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.
Cholestane-3-beta,5-alpha,6-beta-triol
Cutoff: < or =0.070 nmol/mL
7-Ketocholesterol
Cutoff: < or =0.100 nmol/mL
Lyso-sphingomyelin
Cutoff :< or = 0.100 nmol/mL
Interpretation
Provides information to assist in interpretation of the test results
An elevation of cholestane-3-beta, 5-alpha, 6-beta-triol is highly suggestive of Niemann-Pick disease type C (NPC).
An elevation of lyso-sphingomyelin is highly suggestive of Niemann-Pick type A or B (NPA or NPB) disease.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Nonspecific neonatal cholestasis may result in elevations of cholestane-3-beta, 5-alpha, 6-beta-triol and lyso-sphingomyelin 509
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Newborn Screening ACT Sheet [Decreased acid sphingomyelinase] Acid Sphingomyelinase Deficiency (ASMD). American College of Medical Genetics and Genomics; 2022. Revised May 2022. Accessed December 2, 2024. Available at www.acmg.net/PDFLibrary/Niemann-Pick.pdf
2. Wasserstein MP, Schuchman EH. Acid sphingomyelinase deficiency. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews. [Internet]. University of Washington, Seattle; 2006. Updated April 27, 2023. Accessed December 2, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1370/
3. Patterson M. Niemann-Pick disease type C. In: Adam MP, Feldman J, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 10, 2020. Accessed December 2, 2024. Available at www.ncbi.nlm.nih.gov/books/NBK1296/
4. Schuchman EH. The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. Int J Clin Pharmacol Ther. 2009;47(Suppl 1):S48-S57. doi:10.5414/cpp47048
5.. Hollack CEM, de Sonnaville ESV, Cassiman D et al. Acid sphingomyelinase (Asm) deficiency patients in The Netherlands and Belgium: disease spectrum and natural course in attenuated patients. Mol Genet Metab. 2012;107(3):526-533
6. Wasserstein M, Dionisi-Vici C, Giugliani R, et al. Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD). Mol Genet Metab. 2019;126(2):98-105
7. Geberhiwot T, Moro A, Dardis A, et al. International Niemann-Pick Disease Registry (INPDR): Consensus clinical management guidelines for Niemann-Pick disease type C. Orphanet J Rare Dis. 2018;13(1):50
8. Bremova-Ertl T, Claassen J, Foltan T, et al. Efficacy and safety of N-acetyl-L-leucine in Niemann-Pick disease type C. J Neurol. 2022;269(3):1651-1662. doi:10.1007/s00415-021-10717-0
9. Mengel E, Patterson MC, Da Riol RM, et al. Efficacy and safety of arimoclomol in Niemann-Pick disease type C: Results from a double-blind, randomised, placebo-controlled, multinational phase 2/3 trial of a novel treatment. J Inherit Metab Dis. 2021;44(6):1463-1480. doi:10.1002/jimd.12428
Method Description
Describes how the test is performed and provides a method-specific reference
An internal standard is added to an aliquot of plasma, which is then subjected to protein precipitation. Following centrifugation, the supernatant is subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The MS/MS is operated in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for each analyte and internal standard. The ratio of the extracted peak areas to internal standard determined by the LC-MS/MS is used to calculate the concentration of in the sample.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Tuesday, Thursday
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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 account representative. 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. It 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.
CPT codes are provided by the performing laboratory.
82542
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 |
|---|---|---|
| OXNP | Oxysterols, P | 92740-0 |
| 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.
|
|---|---|---|
| 36430 | Cholestane-3beta,5alpha,6beta-triol | 92755-8 |
| 36431 | 7-Ketocholesterol | 92764-0 |
| 36432 | Lyso-sphingomyelin | 92747-5 |
| 36433 | Interpretation (OXNP) | 59462-2 |
| 36434 | Reviewed By | 18771-6 |