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Test ID: KD2T Krabbe Disease Second-Tier Newborn Screen, Blood Spot


Necessary Information


1. Birth weight (grams)

2. Time of birth (24-hour time)

3. Gestational age (weeks)



Specimen Required


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

Collection Container/Tube:

Preferred: Blood Spot Collection Card (T493)

Acceptable: 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. Completely fill at least 3 circles on the filter paper card (approximated 100-microliters blood per circle).

2. Let blood dry on filter paper at room temperature in a horizontal position for 3 or more hours.

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

4. Do not stack wet specimens.

5. Keep specimen dry.

Additional Information:

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

2. 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

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

Method Name

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

Reporting Name

Krabbe Disease 2ND Tier NBS, BS

Specimen Type

Whole blood

Specimen Minimum Volume

2 blood spots

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Ambient (preferred) 96 days
  Frozen  96 days
  Refrigerated  96 days

Clinical Information

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 mutations 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. Ten percent to 15% of individuals have late onset forms of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression presenting anytime from age 6 months to the seventh decade of life.

 

Newborn screening for Krabbe disease has recently 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 and also unaffected patients with GALC pseudodeficiency alleles. For these reasons, second-tier testing that includes both psychosine and 30-kb deletion analyses has been developed. Second-tier testing reduces the number of false-positive results and also 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 mutation (with the exception of late-onset mutations) 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 found. Saposin-A is a sphingolipid activator protein that assists galactocerebrosidase in its action on galactosylceramide.

Reference Values

An interpretive report is provided.

Interpretation

An interpretive report is provided.

 

An elevation of psychosine is indicative of symptomatic Krabbe disease.

 

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

Clinical Reference

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. Wenger DA: Krabbe disease. In GeneReviews University of Washington, Seattle. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Accessed 3/2/2017. Available at ncbi.nlm.nih.gov/books/NBK1238/

4. Wenger DA, Escolar ML, Luzi P, Rafi MA: Krabbe disease (Globoid Cell Leukodystrophy). In The Online Metabolic and Molecular Bases of Inherited Disease. New York, McGraw-Hill, 2014. Edited by D Valle, AL Beaudet, B Vogelstein, et al. Accessed March 02, 2017. Available at ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62644214

Day(s) and Time(s) Performed

Monday through Saturday; 4 p.m., Sunday; 1 p.m.

Analytic Time

1 day

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

82542-Psychosine

81401-30-kb deletion

LOINC Code Information

Test ID Test Order Name Order LOINC Value
KD2T Krabbe Disease 2ND Tier NBS, BS In Process

 

Result ID Test Result Name Result LOINC Value
48536 Interpretation In Process
48535 Reviewed By In Process
BG704 Birth Weight (grams, XXXX) 8339-4
BG705 Time of Birth (24hr Time, XX:XX) 57715-5
BG706 Gestational Age (weeks, XX.X) 76516-4
Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

mml-biochemical