Test Catalog

Test Id : KD2T

Krabbe Disease Second-Tier Newborn Screen, Blood Spot

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

Second-tier testing of newborns with an abnormal screening result for Krabbe disease

 

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

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

This test is used as a second-tier newborn screen for Krabbe disease (galactocerebrosidase deficiency) and includes both psychosine measurement and DNA analysis for the 30-kb deletion.

Highlights

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive lysosomal storage disorder caused by an enzyme deficiency of galactocerebrosidase (GALC).

 

Although Krabbe disease is clinically variable, the most common and severe form of the disorder is early infantile onset that presents with rapid neurological regression and results in early death.

 

Second-tier testing reduces the number of false-positive results reported out.

 

Elevations in psychosine or the presence of a homozygous 30 kilobase deletion of the GALC gene support a diagnosis of Krabbe disease.

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

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

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

Method Name
A short description of the method used to perform the test

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)/Polymerase Chain Reaction with Gel Electrophoresis

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Krabbe Disease 2ND Tier NBS, BS

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

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

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

Specimen Type
Describes the specimen type validated for testing

Whole blood

Necessary Information

1. Birth weight (grams)

2. Time of birth (24-hour time)

3. Gestational age (weeks)

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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

Collection Container/Tube:

Preferred: Blood Spot Collection Card

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

Specimen Volume: 3 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 3 circles on the filter paper card (approximated 100-microliters blood per circle).

3. Let blood dry on 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.

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

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.

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

Blood spot: 2

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Shows serum rings
Insufficient specimen
Layering
Multiple applications
Reject

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
Whole blood Ambient (preferred) 96 days FILTER PAPER
Frozen 96 days FILTER PAPER
Refrigerated 96 days FILTER PAPER

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

Second-tier testing of newborns with an abnormal screening result for Krabbe disease

 

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

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

This test is used as a second-tier newborn screen for Krabbe disease (galactocerebrosidase deficiency) and includes both psychosine measurement and DNA analysis for the 30-kb deletion.

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

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

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 leading to an accumulation of galactosylceramide and severe demyelination throughout the brain. Krabbe disease is primarily caused by variants in the GALC gene, and it has an estimated frequency of 1 in 100,000 births.

 

The clinical course of Krabbe disease can be variable, even within the same family. Eighty-five percent to 90% of patients present before the first year of life with central nervous system impairment including increasing irritability, developmental delay, and sensitivity to stimuli. Rapid neurodegeneration including white matter disease is followed by death usually by age 2. Late onset forms of the disease affect 10% to15% of individuals and are characterized by ataxia, vision loss, weakness, and psychomotor regression typically presenting from age 6 months to the seventh decade of life.

 

Newborn screening for Krabbe disease recently 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.

 

Newborn screening can typically identify patients with Krabbe disease, even before onset of symptoms, as well as unaffected patients with GALC pseudodeficiency alleles. For these reasons, second-tier testing that includes both psychosine and 30-kilobase (kb) deletion analyses has been developed. Second-tier testing reduces the number of false-positive results and limits the identification of affected individuals to patients needing immediate follow-up.

 

Psychosine (PSY), a neurotoxin at elevated concentrations, is 1 of 4 substrates degraded by galactocerebrosidase. It has been shown to be elevated in patients with active disease and, therefore, may be a useful biomarker for the presence of disease or disease progression.

 

The common 30-kb deletion spanning intron 10 through the end of the gene accounts for a significant proportion of disease alleles that contribute to infantile Krabbe disease. While enzyme activity alone 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 genetic variant (with the exception of late-onset genetic variants) are predicted to have infantile Krabbe disease.

 

Although rare, a few infants with an early onset Krabbe disease phenotype due to deficiency of saposin A (SAP-A) have been identified. SAP-A is a sphingolipid activator protein that assists galactocerebrosidase in its action on galactosylceramide.

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

An interpretive report will be provided.

 

An elevation of psychosine is indicative of symptomatic Krabbe disease.

 

The presence of a homozygous 30-kilobase deletion is indicative of early onset Krabbe disease.

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

The absence of the 30-kilobase deletion in the GALC gene does not eliminate the possibility of positive-carrier status or the diagnosis of Krabbe disease. This assay does not include DNA sequencing of the GALC gene.

 

A Krabbe disease phenotype can also be caused by the absence of a physiologically active sphingolipid activator protein, saposin A.

 

Psychosine levels may be normal in patients who are not yet symptomatic or have late onset Krabbe disease.

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

1. Turgeon CT, Orsini JJ, Sanders KA, et al: Measurement of psychosine in dried blood spots-a possible improvement to newborn screening programs for Krabbe disease. J Inherit Metab Dis. 2015 Sep;38(5):923-929

2. Orsini J, Morrissey M, Slavin L, et al: Implementation of newborn screening for Krabbe disease: Population study and cutoff determination. Clin Biochem. 2009;42:877-884

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 June 3, 2021. Available at www.ncbi.nlm.nih.gov/books/NBK1238/

4. Wenger DA, Escolar ML, Luzi P, Rafi MA: Krabbe disease (globoid cell leukodystrophy). In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed June 03, 2021. Available at https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225546481

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

Method Description
Describes how the test is performed and provides a method-specific reference

Protocol 1:

Internal standard is added to a dried blood spot. The extract is evaporated and reconstituted prior to injection onto a liquid chromatography-tandem mass spectrometry (LC-MS/MS). Following separation of the structural isomers glucopsychosine (GPSY) and psychosine by liquid chromatography, their concentrations are measured by MS/MS analysis in the multiple reaction monitoring positive mode to follow the precursor to product species transitions for psychosine (PSY). The ratio of the extracted peak area of PSY to internal standard as determined by LC-MS/MS is used to calculate the concentration of PSY in the sample.(Unpublished Mayo method)

 

Protocol 2:

A polymerase chain reaction-based assay is used to examine DNA for the presence of a 30-kilobase 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

No

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.

Monday through Sunday

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.

1 to 2 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

6 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

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.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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. This test 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.

82542-Psychosine

81401-30-kb deletion

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports