Krabbe Disease via the GALC Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7883 | GALC | 81406 | 81406,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
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 (eg. Satoh et al. Neurology 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 (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, 2008). 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 - Sequencing with CNV PG-Select
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.
Testing Strategy
This test provides full coverage of all coding exons of the GALC gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
A separate test is available to evaluate patients and carriers for the GALC exon 10-17 deletion (see Test #632).
Indications for Test
In vitro galactocerebrosidase enzyme activity in patient leukocytes that is <5% of normal values; infantile onset progressive neurological deterioration; cerebral atrophy. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GALC.
Note that enzyme measurement is not suitable to determine carrier status.
In vitro galactocerebrosidase enzyme activity in patient leukocytes that is <5% of normal values; infantile onset progressive neurological deterioration; cerebral atrophy. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GALC.
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 |
Related Test
| Name |
|---|
| Krabbe Disease via the GALC Exons 11-17 (502T/Del) |
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
Loading...
×
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.