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Test ID: OXNP Oxysterols, Plasma

Useful For

Investigation of possible diagnoses of Niemann-Pick disease type C (NPC) and types A or B (NPA or NPB) in plasma specimens

 

Monitoring of individuals with Niemann-Pick type C disease

Reporting Name

Oxysterols, P

Specimen Type

Plasma


Specimen Required


Collection Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable: Sodium heparin, lithium heparin, ACD A, or ACD B

Submission Container/Tube: Plastic vial

Specimen Volume: 0.3 mL


Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time
Plasma Frozen (preferred) 29 days
  Ambient  14 days
  Refrigerated  14 days

Clinical Information

Niemann-Pick disease types A, B, and C are a group of autosomal recessive lysosomal storage disorders affecting metabolism of specific lipids within cells.

 

Niemann-Pick types A and B (NPA and NPB),(1,2) are caused by a deficiency of sphingomyelinase resulting in extensive storage of sphingomyelin and cholesterol in the liver, spleen, lungs, and, to a lesser degree, brain. Classification of NPA or NPB is based on age of onset as well as the severity of symptoms. NPA disease is more severe and characterized by early onset with feeding problems, , ,  hepatosplenomegaly , cherry red maculae, , developmental arrest and deterioration, hypotonia, and interstitial lung disease. Individuals with NPA typically die by age 3. NPB disease is characterized by later onset and milder symptoms  with survival into adulthood. Some patients have been described with intermediary phenotypes. Characteristic of the disease are large lipid-laden foam cells on bone marrow biopsy.

 

The combined prevalence of NPA and NPB is estimated to be 1 in 250,000. NPA and NPB are inherited in an autosomal recessive manner and are caused by mutations in the SMPD1 gene. Although there is a higher frequency of type A among the Ashkenazi Jewish population, both types are pan-ethnic. Individuals with NPD types A and B typically have elevation of the oxysterol lyso-sphingomyelin (LSM); cholestane-3 beta, 5 alpha, 6 beta-triol and/or 7-ketocholesterol (7-KC) may also be elevated. Molecular genetic testing for NPA and NPB disease is also available (see NPABZ / Niemann-Pick Disease, Types A and B, Full Gene Analysis).

 

Niemann-Pick disease type C (NPC) is caused by a defect in cellular cholesterol trafficking resulting in the accumulation of unesterified cholesterol in late endosomes/lysosomes.(3) Age of onset is variable and ranges from the perinatal period to adulthood, and clinical presentation is also highly variable. Most individuals are diagnosed during childhood with symptoms including ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, and seizures resulting in death by the second or third decade of life. Infants may present with fetal ascites or neonatal liver disease with prolonged jaundice, 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 mutations in either the NPC1 or NPC2 genes. Individuals with NPC exhibit elevated levels of oxysterol cholestane-3 beta,5 alpha,6 beta-triol (COT); 7-ketocholesterol (7-KC) may also be elevated. For molecular confirmation, genetic testing for NPC disease can be performed (see NPCZ / Niemann-Pick Type C Disease, Full Gene Analysis).

Reference Values

CHOLESTANE-3BETA, 5ALPHA, 5BETA-TRIOL

Cutoff: ≤0.02 nmol/mL

 

7-KETOCHOLESTEROL

Cutoff: ≤0.05 nmol/mL

 

LYSO-SPHINGOMYELIN

Cutoff: ≤0.02 nmol/mL

Interpretation

An elevation of cholestane-3 beta, 5 alpha, 6 beta-triol (COT) 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.

Clinical Reference

1. Niemann-Pick Disease Type A. 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/257200?search=257200&highlight=257200

2. Niemann-Pick Disease Type B. 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/607616?search=607616&highlight=607616

3. 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

4. Wasserstein MP, Schuchman EH: Acid sphingomyelinase deficiency. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Retrieved April 7, 2017. Available at www.ncbi.nlm.nih.gov/books/NBK1370/

5. 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, 2014. Accessed April 07, 2017.3. Available at www/ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62643647

6. Gal AE, Brady RO, Hibbert SR, Pentchev PG: A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease. N Engl J Med 1975;293:632-636

7. Patterson M: Niemann-Pick disease type C. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Retrieved April 7, 2017. Available at www.ncbi.nlm.nih.gov/books/NBK1296/

8. Schuchman EH: The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease. Int J Clin Pharmacol Ther 2009;47(Suppl 1):S48-S57

9. Hollack CE, de Sonnaville ES, 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;107:526-533

 

Day(s) and Time(s) Performed

Tuesday, 8 a.m.

Analytic Time

2 days (not reported on Saturday or Sunday)

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

82542

LOINC Code Information

Test ID Test Order Name Order LOINC Value
OXNP Oxysterols, P In Process

 

Result ID Test Result Name Result LOINC Value
36430 Cholestane-3beta,5alpha,6beta-triol In Process
36431 7-Ketocholesterol In Process
36432 Lyso-sphingomyelin In Process
36433 Interpretation (OXNP) 59462-2
36434 Reviewed By No LOINC Needed

Method Name

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

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical