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Test ID: GALCB Galactocerebrosidase, Blood Spot


Specimen Required


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

Container/Tube:

Preferred: Card-Blood Spot Collection (Filter Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, Munktell filter paper, Whatman Protein Saver 903 paper, or blood collected in tubes containing ACD, EDTA, or heparin and dried on acceptable filter paper

Specimen Volume: 2 blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is fingerstick. See Dried Blood Spot Collection Tutorial for how to collect blood spots via fingerstick: https://vimeo.com/508490782 .

2. Completely fill at least 2 circles on the filter paper card (approximately 100 microliters blood per circle).

3. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

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

5. Do not stack wet specimens.

6. Keep specimen dry.

Additional Information:

1. For collection instructions, see Blood Spot Collection Instructions in Special Instructions.

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

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


Forms

Biochemical Genetics Patient Information (T602) in Special Instructions

Useful For

Evaluation of patients with a clinical presentation suggestive of Krabbe disease

 

Longitudinal evaluation of treatment following hematopoietic stem cell transplantation and gene therapy.

Method Name

Flow Injection Analysis-Tandem Mass Spectrometry (FIA-MS/MS)

Reporting Name

Galactocerebrosidase, BS

Specimen Type

Whole blood

Specimen Minimum Volume

1 Blood spot

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole blood Refrigerated (preferred) 56 days FILTER PAPER
  Frozen  56 days FILTER PAPER
  Ambient  7 days FILTER PAPER

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), which can cause 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 have been reported. 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 two years old. 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 several 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. Moreover, in the spring of 2021, the first gene therapy trial was initiated, which may allow for improved outcomes for patients identified before showing clinical symptoms (clinicaltrials.gov).

 

Reduced or absent galactocerebrosidase activity 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 but not to a level to 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, Varies) is necessary for differentiating alterations from disease-causing variants in affected patients and for carrier detection in family members.

Reference Values

Galactocerebrosidase

≥0.4 nmol/mL/hr

Interpretation

An interpretive report will be provided.

 

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), and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

 

Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis based on the analysis, independent biochemical (eg, biomarker such as psychosine) or molecular genetic analysis is required.

Clinical Reference

1. Minter-Baerg M, Stoway SD, Hart J, et al: Precision newborn screening for lysosomal disorders. Genet Med. 2018;20:847-854

2. Guenzel AJ, Turgeon CT, Nickander KK, et al: The critical role of psychosine in screening, diagnosis, and monitoring of Krabbe disease. Genet Med. 2020;22:1108-1118

3. Orsini JJ, Escolar ML, Wasserstein MP, Caggana M: Krabbe disease. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2000. Updated October 11, 2018. Accessed June 29, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1238/

4. 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. doi: 10.1186/s13023-018-0766

Day(s) Performed

Monday through Sunday

Report Available

2 to 8 days

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 US Food and Drug Administration.

CPT Code Information

83789

LOINC Code Information

Test ID Test Order Name Order LOINC Value
GALCB Galactocerebrosidase, BS 62310-8

 

Result ID Test Result Name Result LOINC Value
614799 Interpretation 59462-2
614798 Galactocerebrosidase 62310-8
614800 Reviewed By 18771-6
Mayo Clinic Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical