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Test ID OXNP Oxysterols, Plasma

Useful For

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.

Reporting Name

Oxysterols, P

Specimen Type


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

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° C.

2. Aliquot plasma into plastic vial. Do not disturb the buffy coat layer.

3. Send frozen.

Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Plasma Frozen 65 days

Reject Due To

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK

Clinical Information

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.


NPA and NPB, 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.


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).


NPC is caused by a defect in cellular cholesterol trafficking that results in the progressive accumulation of unesterified cholesterol in late endosomes/lysosomes.(1) 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.


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 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 (NIEM / Niemann-Pick Type C Detection, 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


Cutoff: ≤0.070 nmol/mL



Cutoff: ≤0.100 nmol/mL



Cutoff :≤ 0.100 nmol/mL


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 (LSM) is highly suggestive of Niemann-Pick type A or B (NPA or NPB) disease.


An elevation of LSM 509 is suggestive of NPA, NPB, or NPC disease.


Nonspecific neonatal cholestasis may result in elevations of cholestane-3-beta, 5-alpha, 6-beta-triol and lyso-sphingomyelin 509

Clinical Reference

1.Wasserstein MP, Schuchman EH. Acid sphingomyelinase deficiency. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews [Internet]. University of Washington, Seattle; 2006. Updated February 25,, 2021. Accessed December 12, 2022. Available at

2. Patterson M: Niemann-Pick disease type C. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated December 10, 2020. Accessed December 12, 2022. Available at

3. 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.

4.. 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 Nov;107(3):526-533

5. Wasserstein M, Dionisi-Vici C, Giugliani R, Hwu WL, Lidove O, Lukacs Z, Mengel E, Mistry PK, Schuchman EH, McGovern M. Recommendations for clinical monitoring of patients with acid sphingomyelinase deficiency (ASMD). Mol Genet Metab. 2019 Feb;126(2):98-105. 

6. 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 Apr 6;13(1):50

Method Description

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)

Day(s) Performed

Tuesday, Thursday

Report Available

3 to 7 days

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


LOINC Code Information

Test ID Test Order Name Order LOINC Value
OXNP Oxysterols, P 92740-0


Result ID Test Result Name Result LOINC Value
36433 Interpretation (OXNP) 59462-2
36430 Cholestane-3beta,5alpha,6beta-triol 92755-8
36431 7-Ketocholesterol 92764-0
36432 Lyso-sphingomyelin 92747-5
36434 Reviewed By 18771-6

Method Name

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

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