Krabbe Disease: GALC Gene Deletion/Duplication
Test Code: 4386
Turnaround time: 3 weeks
Krabbe disease is an autosomal recessive neurodegenerative disorder caused by a deficiency of the enzyme galactocerebrosidase. It is part of a group of disorders known as leukodystrophies, which result from the abnormal formation of myelin, the protective covering of nerve cells. When the enzyme galactocerebrosidase is deficient it produces toxic substances in the brain resulting in myelin loss, change to brain cells, and neurological damage.
Krabbe disease is characterized by the onset of progressive neurologic deterioration leading to early death. Symptoms of Krabbe disease usually become apparent before two years of age (85%-90% of individuals) or between six months and the fifth decade for those with slower disease progression (10%-15% of individuals). Early symptoms of Krabbe disease include: irritability, excessive crying, stiffness, arrest of motor and mental development, loss of developmental milestones, feeding difficulties, unexplained fevers, hypersensitivity to stimulus, progressive weight loss, and seizures. As the condition progresses, symptoms may include: back arching, jerking of the arms and legs, severe and rapid deterioration of mental and motor function, loss of vision and hearing, and loss of the ability to move or speak. Neuroimaging studies (MRI and/or CT scans) often reveal progressive, diffuse, and symmetrical cerebral atrophy; however, in the early stage of the disease, the MRI and CT scans can be normal.
Mutations in the GALC gene cause a deficiency of the enzyme galactosylceramidase. Diagnostic sequencing analysis of the GALC gene coding region is available for patients with Krabbe disease and their at-risk relatives on a clinical basis.
1). Wenger DA, Rafi MA, Luzi P (1997) Molecular genetics of Krabbe disease (globoid cell leukodystrophy): diagnostic and clinical implications. Hum Mutat 10:268-79
2). Fu L, Inui K, Nishigaki T, Tatsumi N, Tsukamoto H, Kokubu C, Muramatsu T, Okada S (1999) Molecular heterogeneity of Krabbe disease. J Inherit Metab Dis 22:155-62
3). De Gasperi, R.; Sosa, M. A. G.; Sartorato, E. L.; Battistini, S.; MacFarlane, H.; Gusella, J. F.; Krivit, W.; Kolodny, E. H. Molecular heterogeneity of late-onset forms of globoid-cell leukodystrophy. Am. J. Hum. Genet. 59: 1233-1242, 1996.
- Confirmation of a clinical diagnosis of Krabbe Disease
- Prenatal testing for known familial mutations.
- Assessment of carrier status in high risk family members – known mutation analysis.
DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.
Please note that a “backbone” of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off- target copy number variants causative of disease may be identified that may or may not be related to the patient’s phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient’s clinical and/or biochemical phenotype.
Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood
Type: Whole Blood
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
Submit copies of diagnostic biochemical test results with the sample. Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.
• Known Mutation Analysis (test code: 6875) is available to test family members.