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Test ID: OXYBS Oxysterols, Blood Spot

Useful For

Investigation of possible diagnosis of Niemann-Pick (NP) disease types A, B, or C in blood spot specimens

 

Monitoring of individuals with NP disease type C

Method Name

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

Reporting Name

Oxysterols, BS

Specimen Type

Whole blood


Specimen Required


Supplies:

Card-Blood Spot Collection (Filter Paper) (T493)

Card-Postmortem Screening (Filter Paper) (T525)

Container/Tube:

Preferred: Blood Spot Collection (Filter Paper) (T493)

Acceptable: Ahlstrom 226 filter paper, Munktell filter paper, or Postmortem Screening Card (T525)

Specimen Volume: 2 blood spots

Collection Instructions:

1. Let blood dry on filter paper at room temperature in a horizontal position for 3 or more hours.

2. At least 1 spot should be complete, (ie, unpunched).

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

6. Dried blood spots collected with EDTA, sodium heparin, lithium heparin, or ACD B-containing devices are acceptable.

Additional Information:

1. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

2. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


Specimen Minimum Volume

0.25 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Refrigerated (preferred) 10 days
  Frozen  59 days
  Ambient  10 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 disease types A and B are caused by a deficiency of sphingomyelinase which results in extensive storage of sphingomyelin and cholesterol in the liver, spleen, lungs, and, to a lesser degree, brain. Niemann-Pick type A disease is more severe than type B and characterized by early onset with feeding problems, dystrophy, persistent jaundice, development of hepatosplenomegaly, neurological deterioration, deafness, and blindness leading to death by age 3. Niemann-Pick type B disease is limited to visceral symptoms with survival into adulthood. Some patients have been described with intermediary phenotypes. Characteristic of the disease are large lipid-laden foam cells. Approximately 50% of cases have cherry-red spots in the macula. Sphingomyelinase is encoded by the SMPD1 gene. 

 

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); lsyo-sphingomyelin 509, cholestane-3 beta, 5 alpha, 6 beta-triol (COT), 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)(1) is caused by a defect in cellular cholesterol trafficking that results in the progressive accumulation of unesterified cholesterol in late endosomes/lysosomes. NPC is considered a lipid storage disorder with variable age of onset (range: perinatal period 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 120,000-150,000 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); lyso-sphingomyelin 509 (LSM 509) and7-ketocholesterol (7-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 (see NPCZ / Niemann-Pick Type C Disease, Full Gene Analysis).

Reference Values

Analyte

Cutoff

Cholestane-3beta, 5alpha, 6beta-triol

≤0.800 nmol/mL

Lyso-sphingomyelin

≤0.100 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) disease.

 

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

 

An elevation of lyso-sphingomyelin 509 (LSM 509) is suggestive of NPA, NPB or NPC disease.

Clinical Reference

1. 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

2. 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

3. 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

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. 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):S48-57

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, Thursday; 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
OXYBS Oxysterols, BS In Process

 

Result ID Test Result Name Result LOINC Value
36762 Interpretation (OXYBS) 59462-2
36760 Cholestane-3beta,5alpha,6beta-triol In Process
36761 Lyso-sphingomyelin In Process
36763 Reviewed By 18771-6

Testing Algorithm

See Newborn Screen Follow-up for Niemann Pick Type A and B in Special Instructions.

 

For more information, see Newborn Screening Act Sheet Niemann-Pick A/B Disease: Decreased Acid Sphingomyelinase in Special Instructions.

Forms

If not ordering electronically, complete, print, and send an Inborn Errors of Metabolism Test Request (T798) with the specimen. 

Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical