TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: GALCW    
Galactocerebrosidase, Leukocytes

Useful For Suggests clinical disorders or settings where the test may be helpful

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.

Genetics Test Information Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test provides diagnostic testing for patients with clinical signs and symptoms suspicious for Krabbe disease.

 

Enzyme testing for galactocerebrosidase is included in the diagnostic workup for infants following a positive newborn screen result for Krabbe disease.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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 Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

> or =0.30 nmol/hour/mg protein

An interpretative report will be provided.

Interpretation Provides information to assist in interpretation of the test results

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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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.

 

Enzyme levels may be normal in individuals who have undergone hematopoietic stem cell transplant.

Clinical Reference Recommendations for in-depth reading of a clinical nature

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: Adam MP, Ardinger HH, Pagon RA, et al. eds.GeneReviews. [Internet}University of Washington, Seattle; 2000. Updated October 11, 2018. Accessed March 4, 2019. Available at www.ncbi.nlm.nih.gov/books/NBK1238/

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 doi: /10.1186/s13023-018-0766-x

Special Instructions Library of PDFs including pertinent information and forms related to the test