Test Id : KRABZ
Krabbe Disease, Full Gene Analysis and Large (30 kb) Deletion, Varies
Useful For
Suggests clinical disorders or settings where the test may be helpful
Second-tier test for confirming a diagnosis of Krabbe disease
Carrier testing for individuals with a family history of Krabbe disease in the absence of known sequence variants in the family
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
Testing includes full gene sequencing of the GALC gene.
Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
The following are available:
-Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase
-Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase and Psychosine
If the patient has abnormal newborn screening result for Krabbe disease, immediate action should be taken. Refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1,2)
Method Name
A short description of the method used to perform the test
Polymerase Chain Reaction (PCR) followed by DNA Sequencing
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
B-Galactosidase Galactosylceramide, Leukocytes
Beta-Galactosidase Galactosylceramide, Leukocytes
Cerebroside B-Galactosidase, WBC
Cerebroside Beta-Galactosidase(WBC)
Galactocerebrosidase
Galactocerebrosidase Deficiency
Galactosylceramidase Deficiency
Galactosylceramide
GALC Deficiency
Globoid Cell Leukodystrophy
Krabbe Disease
Krabbe's Disease
GALCS
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
The following are available:
-Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase
-Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase and Psychosine
If the patient has abnormal newborn screening result for Krabbe disease, immediate action should be taken. Refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1,2)
Specimen Type
Describes the specimen type validated for testing
Varies
Ordering Guidance
The recommended first-tier test for Krabbe disease is GALCW / Galactocerebrosidase, Leukocytes, however this test is not reliable for detection of carriers.
For ongoing therapeutic monitoring for patients with Krabbe disease or for second tier newborn screening, order PSY / Psychosine, Blood Spot.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube:
Preferred: Lavender top (EDTA) or yellow top (ACD)
Acceptable: Any anticoagulant
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send specimen in original tube.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Specimen Type: Cultured fibroblasts
Container/Tube: T-75 or T-25 flask
Specimen Volume: 1 Full T-75 or 2 full T-25 flasks
Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Acceptable:
Specimen Type: Blood spot
Supplies: Card - Blood Spot Collection (Filter Paper) (T493)
Container/Tube:
Preferred: Collection card (Whatman Protein Saver 903 Paper)
Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper or blood spot collection card
Specimen Volume: 2 to 5 Blood spots
Collection Instructions:
1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.
2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.
3. Do not expose specimen to heat or direct sunlight.
4. Do not stack wet specimens.
5. Keep specimen dry.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information:
1. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.
2. For collection instructions, see Blood Spot Collection Instructions
3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Special Instructions
Library of PDFs including pertinent information and forms related to the test
- Molecular Genetics: Biochemical Disorders Patient Information
- Informed Consent for Genetic Testing
- Blood Spot Collection Card-Spanish Instructions
- Blood Spot Collection Card-Chinese Instructions
- Informed Consent for Genetic Testing (Spanish)
- Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase
- Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase and Psychosine
- Blood Spot Collection Instructions
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. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions
3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
Blood: 1 mL
Blood Spots: 3
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Useful For
Suggests clinical disorders or settings where the test may be helpful
Second-tier test for confirming a diagnosis of Krabbe disease
Carrier testing for individuals with a family history of Krabbe disease in the absence of known sequence variants in the family
Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request
Testing includes full gene sequencing of the GALC gene.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
The following are available:
-Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase
-Newborn Screen Follow-up for Krabbe Disease: Galactocerebrosidase and Psychosine
If the patient has abnormal newborn screening result for Krabbe disease, immediate action should be taken. Refer to the appropriate American College of Medical Genetics and Genomics Newborn Screening ACT Sheet.(1,2)
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 galactocerebrosidase (GALC, galactosylceramide beta-galactosidase). GALC is encoded by the GALC gene located on 14q31. Krabbe disease occurs in approximately 1 in 100,000 live births with a carrier frequency of about 1 in 150 in the general population. Deficiency of GALC activity leads to an accumulation of galactosylceramide in globoid cells (multinucleated macrophages) causing severe demyelination throughout the brain. The toxic metabolite galactosylsphingosine (psychosine), an apoptotic compound, accumulates in oligodendrocytes and Schwann cells and contributes to disease pathogenicity.
Severely affected individuals typically present between 3 to 6 months of age with increasing irritability and sensitivity to stimuli. Rapid neurodegeneration follows, with death usually occurring by age 13 months. There are later onset forms of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression. The clinical course of Krabbe disease can be variable even within the same family. Treatment is mostly supportive, although hematopoietic stem cell transplantation has shown some success if treatment begins before neurologic damage has occurred.
The recommended first-tier test for Krabbe disease is GALCW / Galactocerebrosidase, Leukocytes.
Individuals with GALC activity below the reference range for these assays are more likely to have variants in the GALC gene that are identifiable by molecular genetic testing. The above test is not reliable for detection of carriers of Krabbe disease. Additionally, measurement of the psychosine biomarker can aid in diagnosis and ongoing therapeutic monitoring (PSY / Psychosine, Blood Spot).
This assay includes DNA sequencing of all 17 exons within the GALC gene as well as evaluation for the common 30-kb deletion spanning intron 10 through the end of the gene. This deletion accounts for a significant proportion of disease alleles that contribute to infantile Krabbe disease. While enzyme activity is not predictive of age of onset, there are known genotype-phenotype correlations. Individuals who are homozygous for the deletion or compound heterozygous for the deletion and a second GALC alteration (with the exception of late-onset variants) are predicted to have infantile Krabbe disease. The c.857G->A (p.Gly286Asp) alteration, on the other hand, is only associated with a late-onset phenotype.
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.
An interpretive report will be provided.
Interpretation
Provides information to assist in interpretation of the test results
All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(3) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This analysis does not exclude a diagnosis of atypical Krabbe disease due to saposin A deficiency.
A small percentage of individuals who are carriers or have a diagnosis of Krabbe disease may have a variant that is not identifiable by this method (eg, large genomic deletions, promoter alterations). The absence of a variant, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of Krabbe disease.
In some cases, DNA alterations of undetermined significance may be identified.
Rare alterations exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Newborn Screening ACT Sheet [Decreased galactocerebrosidase, elevated psychosine] Krabbe Disease (infantile form). American College of Medical Genetics and Genomics; 2021. Updated May 2022. Accessed June 10, 2024. Available at www.acmg.net/PDFLibrary/Krabbe-Infantile.pdf
2. Newborn Screening ACT Sheet [Decreased galactocerebrosidase, mildly elevated psychosine] Krabbe Disease (late-onset form). American College of Medical Genetics and Genomics; 2021. Updated May 2022. Accessed June 10, 2024. Available www.acmg.net/PDFLibrary/Krabbe-Later-Onset.pdf
3. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424
4. 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 30, 2020. Available at ncbi.nlm.nih.gov/books/NBK1238/
5. Luzi P, Rafi MA, Wenger DA: Structure and organization of the human galactocerebrosidase (GALC) gene. Genomics. 1995;26:407-409
6. Luzi P, Rafi MA, Wenger DA: Characterization of the large deletion in the GALC gene found in patients with Krabbe disease. Hum Mol Genet. 1995;4(12):2335-2338
7. Spiegel R, Bach G, Sury V, et al: A mutation in the saposin A coding region of the prosaposin gene in an infant presenting as Krabbe disease: report of saposin A deficiency in humans. Molec Genet Metab. 2005,84:160-166
Method Description
Describes how the test is performed and provides a method-specific reference
Bidirectional sequence analysis is performed to test for the presence of a sequence variant in all coding regions and intron/exon boundaries of the GALC gene. Additionally, a PCR-based assay is used to examine DNA for the presence of a 30-kb deletion encompassing exon 11 through the end of the GALC gene.(Unpublished Mayo method)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Varies
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
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Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
81406 GALC (galactosylceramidase) (eg, Krabbe disease), full gene sequence
88233-Tissue culture, skin or solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| KRABZ | Krabbe Disease, Full Gene Analysis | 87738-1 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 53505 | Result Summary | 50397-9 |
| 53506 | Result | 82939-0 |
| 53507 | Interpretation | 69047-9 |
| 53508 | Additional Information | 48767-8 |
| 53509 | Specimen | 31208-2 |
| 53510 | Source | 31208-2 |
| 53511 | Released By | 18771-6 |