Test ID: PSYCF Psychosine, Spinal Fluid
Shipping Instructions
Send on dry ice. Avoid freeze thaw cycles.
Necessary Information
1. Patient’s age is required.
2. Date of hematopoietic stem cell transplantation (HSCT), if performed.
Specimen Required
Collection Container/Tube: Sterile vial.
Specimen Volume: 0.150 mL
Collection Instructions: Do not aliquot.
Useful For
Aids in the biochemical diagnosis of Krabbe disease using cerebrospinal fluid specimens
Follow-up of individuals affected with Krabbe disease
Follow-up testing after an abnormal newborn screening result for Krabbe disease
Monitoring of individuals at risk to develop late onset Krabbe disease
Monitoring of individuals with Krabbe disease after hematopoietic stem cell transplantation
Method Name
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
Reporting Name
Psychosine, CSFSpecimen Type
CSFSpecimen Minimum Volume
0.100 mL
Specimen Stability Information
Specimen Type | Temperature | Time | Special Container |
---|---|---|---|
CSF | Frozen | 7 days |
Clinical Information
Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive lysosomal disorder caused by deficient activity of the enzyme galactocerebrosidase (GALC). GALC facilitates the lysosomal degradation of psychosine (galactosylsphingosine) and 3 other substrates (galactosylceramide, lactosylceramide, and lactosylsphingosine). Krabbe disease is caused by mutations in the GALC gene, and it has an estimated frequency of 1 in 250,000 births.
Eighty-five percent to 90% of patients present before the first year of life with central nervous system impairment including increasing irritability, developmental delay, and sensitivity to stimuli. Rapid neurodegeneration including white matter disease follows, with death usually occurring by 2 years of age. Ten percent to 15% of individuals have later onset variants of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression, presenting anytime from 6 months to the seventh decade of life. The clinical course of Krabbe disease can be variable, even within the same family.
Newborn screening for Krabbe disease has been implemented in some states. The early (presymptomatic) identification and subsequent testing of infants at risk for Krabbe disease may be helpful in reducing the morbidity and mortality associated with this disease. While treatment is mostly supportive, hematopoietic stem cell transplantation has shown some success if performed prior to onset of neurologic damage.
Psychosine (PSY) is a neurotoxin at elevated concentrations. Importantly, it is 1 of 4 substrates degraded by GALC. It has been shown to be elevated in patients with active Krabbe disease or with Saposin A cofactor deficiency, and therefore, may be a useful biomarker for the presence of disease or disease progression.
Reduced or absent GALC in leukocytes (CBGC / Galactocerebrosidase, Leukocytes) or dried blood spots (PLSD / Lysosomal and Peroxisomal Storage Disorders Screen, Blood Spot) along with psychosine analysis can indicate a diagnosis of Krabbe disease. Molecular sequencing of the GALC gene (KRABZ / Krabbe Disease, Full Gene Analysis and Large [30 kb] Deletion, PCR) allows for detection of the disease-causing mutations in affected patients and carrier detection in family members.
Individuals with a disease phenotype similar to Krabbe disease may have Saposin A cofactor deficiency. Saposin A cofactor deficiency also results in elevated psychosine levels. Testing for this condition via molecular analysis of PSAP is useful in those with elevated psychosine and normal to reduced GALC activity with normal molecular genetic GALC analysis.
Reference Values
Normal < 0.04 nmol/L
Interpretation
An elevation of psychosine is indicative of Krabbe disease or Saposin A cofactor deficiency.
Clinical Reference
1. Kwon JM, Matern D, Kurtzberg J, et al: Consensus guidelines for newborn screening, diagnosis and treatment of infantile Krabbe disease. Orphanet J Rare Dis. 2018;13(1):30 doi: 10.1186/s13023-018-0766-x
2. Orsini JJ, Escolar ML, Wasserstein MP, et al: Krabbe Disease. In GeneReviews Edited by: MP Adam, HH Ardinger, RA Pagon: University of Washington, Seattle. 1993-2019. 2000 Jun 19 [Updated 2018 Oct 11]. Accessed May 2019. Available at: www.ncbi.nlm.nih.gov/books/NBK1238/
3. Turgeon CT, Orsini JJ, Sanders KA, et al: Measurement of psychosine in dried blood spots - a possible improvement to newborn screening programs for Krabbe disease. J Inherit Metab Dis. 2015;38: 923–929
4. Wenger DA, Escolar ML, Luzi P, Rafi MA: Krabbe disease (Globoid Cell Leukodystrophy). In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL BeaudetL, B Vogelstein, KW Kinzler, SE Antonarakis, A Ballabio, K Gibson, G Mitchell. New York, NY: McGraw-Hill; 2014 Accessed March 20, 2019. Available at: http://ommbid.mhmedical.com/content.aspx?bookid=971§ionid=62644214
Day(s) and Time(s) Performed
Tuesday, Thursday; 8 a.m.
Analytic Time
3 daysTest 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 |
---|---|---|
PSYCF | Psychosine, CSF | 93686-4 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
606150 | Interpretation (PSYCF) | 59462-2 |
606146 | Psychosine, CSF | 93686-4 |
605158 | Reviewed By | 18771-6 |
mml-biochemical