Krabbe Disease via the GALC Exons 11-17 (502T/Del)

Summary and Pricing

Test Method

Targeted Deletion Testing via PCR
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
632 GALC 81401 81401 $250 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
632GALC81401 81401(x1) $250 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Jana Paderova, PhD

Clinical Features and Genetics

Clinical Features

Krabbe disease or globoid cell leukodystrophy (OMIM 245200) results from deficiency of galactocerebrosidase, a lysosomal enzyme involved in the metabolism of galactosylceramide. Galactosylceramide is a component of the myelin sheath, and with deficient galactocerebrosidase activity, this complex lipid is known to accumulate in globoid cells. Accompanying the appearance of globoid cells is loss of myelin and associated progressive neurological deterioration leading to death (Wenger et al. in Scriver et al. Metabolic and molecular bases of inherited disease, 3669-3694, 2001). Most cases present in early infancy with nonspecific signs such as irritability and delays in reaching developmental milestones. The clinical course is rapid, spanning 1 to 3 years and includes hypersensitivity to external stimuli, hypertonicity, motor and mental deterioration, blindness, and deafness. Less commonly the disease presents later in life with neurological signs including weakness, vision loss, and mental changes (Satoh et al. Neurol 49:1392-1399, 1997; Kolodny et al. Dev Neurosci 13:232-239, 1991). Disease progression in later-onset cases is typically protracted although an initial rapid deterioration is common (Loonen et al. Neuropediatrics 16:137-142, 1985).

Genetics

Krabbe disease is inherited in an autosomal recessive manner. Intrafamilial variability of the clinical symptoms occurs. Over 50 GALC variants, mostly missense, have been reported. The most common variant in patients of European descent, however, is a large deletion encompassing exons 11 through 17 of GALC (Luzi et al. Hum Mol Genet 4:2335-2338, 1995; Rafi et al. Hum Mol Genet 4:1285-1289, 1995). This deletion (referred to as 502T/del) accounts for approximately 50% of all disease alleles in northern European patients (Kleijer et al. J Inherit Metab Dis 20:587-594, 1997), and is similarly common in patients from the USA, including those with Mexican ancestry (Wenger, Krabbe Disease, GeneReviews, 2007). Late-onset cases frequently have at least one copy of the c.809G>A (p.Gly270Asp) variant (Kolodny et al. Am J Hum Genet 57:A217, 1995).Galactocerebrosidase is coded by exons 1-17 of the GALC gene on chromosome 14q31.

Clinical Sensitivity - Targeted Deletion

Diminished galactocerebrosidase activity due to GALC variants is the only cause of Krabbe disease and late-onset globoid cell leukodystrophy. Analytical sensitivity for deletion testing and sequence analysis should be high in cases with demonstrated enzyme deficiency. The exon 11-17 deletion accounts for approximately half of all disease alleles.

Testing Strategy

Testing involves determination of the 502T/del status as described by Luzi et al. (Hum Mol Genet 4:2335-2338, 1995). A separate test is available to evaluate the entire GALC coding region by direct sequence analysis (see Test #631).

Indications for Test

In vitro galactocerebrosidase enzyme activity in patient leukocytes that is <5% of normal values; infantile onset progressive neurological deterioration; cerebral atrophy.Note that enzyme measurement is not suitable to determine carrier status.

Gene

Official Gene Symbol OMIM ID
GALC 606890
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Galactosylceramide Beta-Galactosidase Deficiency AR 245200

Citations

  • David A Wenger (2008). "Krabbe Disease." PubMed ID: 20301416
  • EH Kolodny, et.al. (1995). "Molecular genetics of late-onset Krabbe disease." Posters: Molecular Etiology of Disease A217.
  • Kleijer, W. J., et.al. (1997). "Prevalent mutations in the GALC gene of patients with Krabbe disease of Dutch and other European origin." J Inherit Metab Dis 20(4): 587-94. PubMed ID: 9266397
  • Kolodny, E. H., et.al. (1991). "Late-onset Krabbe disease (globoid cell leukodystrophy): clinical and biochemical features of 15 cases." Dev Neurosci 13(4-5): 232-9. PubMed ID: 1817026
  • Loonen, M. C., et.al. (1985). "Late-onset globoid cell leucodystrophy (Krabbe PubMed ID: 4047347
  • Luzi, P., et.al. (1995). "Characterization of the large deletion in the GALC gene found in patients with Krabbe disease." Hum Mol Genet 4(12): 2335-8. PubMed ID: 8634707
  • Rafi, M. A., et.al. (1995). "A large deletion together with a point mutation in the GALC gene is a common mutant allele in patients with infantile Krabbe disease." Hum Mol Genet 4(8): 1285-9. PubMed ID: 7581365
  • Satoh, J. I., et.al. (1997). "Adult-onset Krabbe disease with homozygous T1853C mutation in the galactocerebrosidase gene. Unusual MRI findings of corticospinal tract demyelination." Neurology 49(5): 1392-9. PubMed ID: 9371928
  • Wenger et al. In: The Metabolic and Molecular Basis of Inherited Disease - 8th edition (edited by C.R. Scriver et al.) New York: McGraw-Hill.  2:3669-3694.

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
×
Copy Text to Clipboard
×