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Test Code CBGC Galactocerebrosidase, Leukocytes

Performing Laboratory

Mayo Medical Laboratories in Rochester

Reporting Name

Galactocerebrosidase, WBC

Specimen Type

Whole Blood ACD


Shipping Instructions


For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerate within 72 hours of draw to be stabilized. Draw specimen Monday through Thursday only and not the day before a holiday. Specimen should be drawn 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)

Specimen Volume: 6 mL

Collection Instructions: Do not transfer blood to other containers.


Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

NA

Icterus

NA

Other

NA

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood ACD Refrigerated (preferred) 72 hours
  Ambient  72 hours

Specimen Minimum Volume

5 mL

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday. Assay is performed: Varies

Specimen Retention Time

WBC homogenate stored 1 month

Analytic Time

9 days

Reference Values

≥1.20 nmol/h/mg protein

Useful For

Diagnosis of Krabbe disease

Testing Algorithm

See Newborn Screen Follow-up for Infantile Krabbe Disease in Special Instructions.

 

For more information, see Newborn Screening Act Sheet Krabbe Disease: Decreased Galactocerebrosidase in Special Instructions.

Method Name

Radioisotopic

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

82658

LOINC Code Information

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

 

Result ID Test Result Name Result LOINC Value
35584 Galactocerebrosidase, WBC 24084-6
35585 Interpretation (CBGC) 59462-2
35586 Reviewed By No LOINC Needed

Clinical Information

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive disorder caused by a deficiency of galactocerebrosidase. A deficiency of this enzyme leads to an accumulation of galactosylceramide causing severe demyelination throughout the brain. Krabbe disease is primarily caused by mutations 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 polymorphisms in the GALC gene have been identified that result in reduced galactocerebrosidase activity in vitro, but do not cause disease. Molecular sequencing of the GALC gene (KRABZ / Krabbe Disease, Full Gene Analysis and Large [30 kb] Deletion, PCR) is necessary for differentiating polymorphisms from disease-causing mutations in affected patients and for carrier detection in family members.

Interpretation

Values below the reference range are consistent with a diagnosis of Krabbe disease.

Cautions

This test is not recommended for carrier detection because of the wide range of enzymatic activities observed in carriers and noncarriers.

 

Pseudodeficiency of galactocerebrosidase causes reduced enzymatic activity, but does not cause disease.

 

A Krabbe disease phenotype can also be caused in very rare cases by the absence of a physiologically active sphingolipid activator protein, saposin A (SAP-A).

Clinical Reference

1. Wenger DA: Krabbe Disease. 2000 Jun 19 (Updated 2011 Mar 31). Edited by RA Pagon, MP Adam, HH Ardinger, GeneReviews. University of Washington, Seattle, 1993-2017. Accessed March 27, 2017, Available at www.ncbi.nlm.nih.gov/books/NBK1238/

2. 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 Beaudet, B Vogelstein, et al. New York, McGraw-Hill; 2014. Accessed March 27, 2017. Available at ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62644214 

3. Graziano AC, Cardile V: History, genetic, and recent advances on Krabbe disease. Gene 2015 Jan 15;555(1):2-13 4. Orsini JJ, Kay DM, Saavedra-Matiz CA, et al: Newborn screening for Krabbe disease in New York State: the first eight years' experience. Genet Med 2016 Mar;18(3):239-248

Method Description

The natural substrate, galactosylceramide (galactocerebroside), is used in this assay. The galactose moiety of the substrate is labeled with tritium. The liberated (3)H galactose is determined after it is separated from the unreacted galactosylceramide by solvent partitioning.(Suzuki K: Enzymic diagnosis of sphingolipidoses: globoid cell leukodystrophy [Krabbe's disease]. Methods Enzymol 1979;50:456-488; Radin NS: Labeled galactosyl ceramide and lactosyl ceramide. Methods Enzymol 1972;28:300-306)

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

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

Genetics Test Information

Diagnostic testing for patients with clinical signs and symptoms suspicious for Krabbe disease.

 

Included in the diagnostic workup for infants following a positive newborn screen result for Krabbe disease.

This test is not intended for carrier detection.