Krabbe Disease: GALC Sequencing

Turnaround Time

3 weeks

CPT Code(s)

81406

Cost

$1,000

Genes

• Krabbe Disease also Galactocerebrosidase Deficiency

Krabbe disease leads to the accumulation of galactosylceramide specifically in brain white matter, causing a neurological phenotype. Patients with the severe, infantile form of Krabbe disease will typically present by 3-6 months of age with rapidly progressive neurodegeneration, muscle rigidity, seizures, irritability, vomiting, and blindness and/or deafness. Approximately 10-15% of cases exhibit a milder, late onset clinical phenotype, with patients presenting with general weakness or stiffness, ataxia, vision loss, and some intellectual regression.

The enzyme assay for galactocerebrosidase activity is considered diagnostic for Krabbe Disease. However, the enzyme assay is not a reliable method for carrier detection. Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Sanger Sequencing

This analysis includes full sequencing of the coding region of the GALC gene as well as allele-specific PCR to detect the common 30 kb deletion in this gene. These two methods combined are expected to detect close to 100% of the abnormal alleles in individuals with a biochemical diagnosis.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA, dried blood spots, and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.