Krabbe Disease via the GALC Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
631 GALC$910.00 81406 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Diminished Galactocerebrosidase activity due to GALC mutations 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.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 GALC$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

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 non specific 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).


Krabbe Disease is inherited in an autosomal recessive manner. Intrafamilial variability of the clinical symptoms occurs. Over 50 GALC mutations, mostly missense, have been reported. The most common mutation in patients of European decent, 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 a c.809G>A (p.Gly270Asp) mutation (Kolodny et al. Am J Hum Genet 57:A217, 1995).

Galactocerebrosidase is coded by exons 1-17 of the GALC gene on chromosome 14q31.

Testing Strategy

This test involves bidirectional DNA sequencing of all coding exons and splice sites of the GALC gene.  The full coding sequence of each exon plus ~10 bp of flanking DNA on either side are sequenced.  We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.

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.

Note that enzyme measurement is not suitable to determine carrier status.


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


Name Inheritance OMIM ID
Galactosylceramide Beta-Galactosidase Deficiency 245200

Related Test

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


Genetic Counselors
  • David A Wenger (2008). "Krabbe Disease." PubMed ID: 20301416
  • EH Kolodny, (1995). "Molecular genetics of late-onset Krabbe disease." Posters: Molecular Etiology of Disease A217.
  • Kleijer, W. J., (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., (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., (1985). "Late-onset globoid cell leucodystrophy (Krabbe PubMed ID: 4047347
  • Luzi, P., (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., (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., (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.
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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