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GTR Home > Tests > GALC Gene Sequencing

Indication

This is a clinical test intended for Help: Diagnosis, Risk Assessment

Clinical summary

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Imported from GeneReviews

Krabbe disease comprises a spectrum ranging from infantile-onset disease (i.e., onset of extreme irritability, spasticity, and developmental delay before age 12 months) to later-onset disease (i.e., onset of manifestations after age 12 months and as late as the seventh decade). Although historically 85%-90% of symptomatic individuals with Krabbe disease diagnosed by enzyme activity alone have infantile-onset Krabbe disease and 10%-15% have later-onset Krabbe disease, the experience with newborn screening (NBS) suggests that the proportion of individuals with possible later-onset Krabbe disease is higher than previously thought. Infantile-onset Krabbe disease is characterized by normal development in the first few months followed by rapid severe neurologic deterioration; the average age of death is 24 months (range 8 months to 9 years). Later-onset Krabbe disease is much more variable in its presentation and disease course.

Clinical features

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Imported from Human Phenotype Ontology (HPO)

  • Decerebrate rigidity
  • Hydrocephalus
  • Hypertonia
  • Hypotonia
  • Neurodegeneration
  • Nystagmus
  • Optic atrophy
  • Seizure
  • Vomiting
  • EEG abnormality
  • Autoimmune thrombocytopenia
  • CNS demyelination
  • Blindness
  • Diffuse cerebral atrophy
  • Peripheral demyelination
  • Sensorimotor neuropathy
  • Hearing impairment
  • Increased CSF protein concentration
  • Developmental regression
  • Hyperactive deep tendon reflexes
  • Axial hypotonia
  • Decreased nerve conduction velocity
  • Progressive spasticity
  • Motor deterioration
  • Failure to thrive
  • Recurrent fever
  • Abnormal flash visual evoked potentials
  • Reduced galactocerebrosidase activity
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Inheritance pattern

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Autosomal recessive inheritance

Conditions tested

Target population

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Individuals suspected to have Krabbe Disease (galactocerebrosidase deficiency, or GALC deficiency). Individuals with whose reproductive partner is a known carrier of disease-causing variant in the GALC gene (e.g. common 30-kb deletion)

Clinical validity

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This test sequences the entire coding regions of the GALC gene by Sanger sequencing method. About 55-65% of patients with Krabbe disease have a pathogenic variant detectable by GALC gene sequencing.

Citations

Not provided

Clinical utility

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Establish or confirm diagnosis

Reproductive decision-making

Practice guidelines

  • ACMG ACT, 2022
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased galactocerebrosidase, elevated psychosine, Krabbe Disease (infantile form), 2022
  • ACMG Algorithm, 2022
    American College of Medical Genetics and Genomics, Algorithm, Krabbe disease: galactocerebrosidase deficiency, 2022
  • ACMG ACT, 2022
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Decreased galactocerebrosidase, mildly elevated psychosine, Krabbe Disease (late-onset form), 2022
  • AAP, 2021
    Leukodystrophies in Children: Diagnosis, Care, and Treatment, Pediatrics (2021) 148 (3): e2021053126.

IMPORTANT NOTE: NIH does not independently verify information submitted to the GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in the GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.