Invitae Krabbe Disease Test


Test description

The Invitae Krabbe Disease Test sequences the GALC gene. Pathogenic variants in GALC lead to Krabbe disease, which is caused by deficient activity of the lysosomal hydrolase galactosylceramide beta-galactosidase. An individual with Krabbe disease is either homozygous or a compound heterozygote for pathogenic variants in GALC.

Several US states currently include screening for Krabbe disease on their newborn screening panels by enzymatic analysis of galactocerebrosidase. GALC testing is intended for babies who test positive on newborn screening and for individuals in whom Krabbe disease is suspected. Krabbe disease may also be indicated by abnormal brain MRI images or cerebrospinal fluid protein levels. The early infantile form is rapidly progressive and usually fatal. Later-onset Krabbe disease may have a more slowly progressive and milder course.

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Primary panel (1 gene)


GALC: Analysis includes the large (30 kb) deletion for Krabbe Disease.

Krabbe disease

Krabbe disease is a rare progressive neurodegenerative lysosomal storage disorder whose main feature is leukodystrophy. There are four forms of Krabbe disease: early infantile, later onset, adolescent, and adult. The infantile form manifests at a few months of life with feeding problems, gastroesophageal reflux, irritability, and clasped thumbs. Increased muscle tone (hypertonicity) can be seen in the initial phase of disease, but it is followed by low muscle tone (hypotonia). Seizures are a common feature in affected infants, who usually die before the age of 2 years. There is no enzyme replacement available. Hematopoietic stem cell transplant (HSCT) before the onset of symptoms currently provides the only treatment option.

Later onset should be considered in individuals who exhibit a loss of milestones and whose brain MRIs show evidence of leukodystrophy. The affected individuals present with visual loss and difficulty with walking. Signs and symptoms in the later-onset group are variable. HSCT in older, mildly affected individuals has been undertaken; some individuals are said to have shown improvement, and others show less-serious progression of disease.

Pathogenic variants in the GALC gene are the only known cause of Krabbe disease. Most affected individuals are identified when sequencing and del/dup testing are performed. 85%–90% of affected individuals have the early infantile form. 45% of pathogenic variants of European descent and 35% of the affected individuals of Mexican descent have a 30 kb deletion. In later-onset cases, the pathogenic variant c.857G>A is often found.

Krabbe disease is inherited in an autosomal recessive manner.

Krabbe disease occurs about 1 in 100,000 births in the US and Europe, with higher incidence among consanguineous populations in Israel (6 in 1000 births).

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
GALC* NM_000153.3

GALC: Analysis includes the large (30 kb) deletion for Krabbe Disease.