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Test Code GALCW Galactocerebrosidase, Leukocytes


Advisory Information


This test will not detect carrier status. For differentiating alterations from disease-causing variants in affected patients and for carrier detection in family members, molecular sequencing of the GALC gene is necessary. Order KRABZ / Krabbe Disease, Full Gene Analysis and Large (30 kb) Deletion, PCR, Varies.



Shipping Instructions


For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerate within 96 hours of collection to be stabilized. Collect specimen Monday through Thursday only and not the day before a holiday. Specimen should be collected and packaged as close to shipping time as possible.



Specimen Required


Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Yellow top (ACD solution A) or lavender top (EDTA)

Specimen Volume: 6 mL

Collection Instructions: Send specimen in original tube. Do not transfer blood to other containers.


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2.Biochemical Genetics Patient Information (T602) in Special Instructions

Secondary ID

606270

Useful For

Diagnosis of Krabbe disease

 

Follow-up testing for evaluation of an abnormal newborn screening result for Krabbe disease

 

This test is not intended for carrier detection.

Method Name

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

Reporting Name

Galactocerebrosidase, WBC

Specimen Type

Whole Blood ACD

Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole Blood ACD Refrigerated (preferred) 4 days
  Ambient  72 hours

Reject Due To

Gross hemolysis Reject

Clinical Information

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder caused by a deficiency of the enzyme, galactocerebrosidase (GALC). GALC facilitates the lysosomal degradation of psychosine (galactosylsphingosine) and 3 other substrates (galactosylceramide, lactosylceramide and lactosylsphingosine causing severe demyelination throughout the brain. Krabbe disease is caused by variants in the GALC gene, and it has an estimated frequency of 1 in 100,000 births. Although rare, a few infants with an early onset Krabbe disease phenotype due to deficiency of saposin A (SAP-A) have been found. Saposin-A is a sphingolipid activator protein that assists galactocerebrosidase in its action on galactosylceramide.

 

Severely affected individuals typically present between 3 to 6 months of age with increasing irritability and sensitivity to stimuli. Rapid neurodegeneration including white matter disease follows with death usually occurring by age 2. Some individuals have later onset forms of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression presenting anywhere from age 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.

 

Reduced or absent galactocerebrosidase in leukocytes can indicate a diagnosis of Krabbe disease, however a number of alterations in the GALC gene have been identified that result in reduced galactocerebrosidase activity in vitro, but do not cause disease. The biomarker, psychosine (see PSY / Psychosine, Blood Spot) has been shown to be elevated in patients with active Krabbe disease. Molecular sequencing of the GALC gene (see KRABZ / Krabbe Disease, Full Gene Analysis and Large [30 kb] Deletion, PCR, Varies) is necessary for differentiating alterations from disease-causing variants in affected patients and for carrier detection in family members.

Reference Values

≥0.30 nmol/hour/mg protein

An interpretative report will be provided.

Interpretation

When abnormal results are detected, a detailed interpretation is given, including an overview of the results and of their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing, and in vitro, confirmatory studies (enzyme assay, molecular analysis), name and phone number of key contacts who may provide these studies, and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

Clinical Reference

1. Elliott S, Buroker N, Cournoyer JJ, et al: Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry. Mol Genet Metab 2016 Aug;118(4):304-309

2. Matern D, Gavrilov D, Oglesbee D, et al: Newborn screening for lysosomal storage disorders. Semin Perinatol 2015 Apr;39(3):206-216

3. Orsini JJ, Escolar ML, Wasserstein MP, et al: Krabbe Disease. In GeneReviews. Edited by MP Adam, HH Ardinger, RA Pagon, et al. Seattle (WA): University of Washington. Updated 2018 Oct 11. Available at https://www.ncbi.nlm.nih.gov/books/NBK1238/. Accessed March 4, 2019

4. Liao HC, Spacil Z, Ghomashchi F, et al: Lymphocyte Galactocerebrosidase Activity by LC-MS/MS for Post-Newborn Screening Evaluation of Krabbe Disease. Clin Chem 2017 Aug;63(8):1363-1369

5. Kwon JM, Matern DM, Kurtzberg J, et al: Consensus Guidelines for Newborn Screening, Diagnosis and Treatment of Infantile Krabbe Disease. Orphanet J Rare Dis 2018;13:30. Available at: https://doi.org/10.1186/s13023-018-0766-x

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday.

Assay is performed: Varies

Analytic Time

5 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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

82657

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GALCW Galactocerebrosidase, WBC 24084-6

 

Result ID Test Result Name Result LOINC Value
606270 Galactocerebrosidase, WBC 24084-6
606271 Interpretation 59462-2
606272 Reviewed By 18771-6