β-galactocerebrosidase (Krabbe Disease)
Related Gene(s): GALC
Krabbe disease is a lysosomal disorder that affects the central and peripheral nervous systems. The disease affects approximately 1 in 100,000 individuals in the general population, with a higher incidence being reported in several Israeli communities. The condition is inherited in an autosomal recessive pattern and is caused by a deficiency of the galactocerebrosidase (galactosylceramidase) enzyme, which leads to accumulation of galactosylceramide and galactosylsphingosine (psychosine). This results in the formation of globoid cells and impaired growth and maintenance of myelin.
The majority of individuals will present within their first 6 months of life with the “infantile” or “classic” form of the condition, with symptoms such as irritability, spasticity, and developmental delay. Severe motor and mental deterioration ultimately leads to death by 2 years old. Approximately 10-15% of patients will present with the later-onset forms of the disease which present with less severe symptoms and slower progression. Krabbe disease symptoms can be variable, even within a family.
Diagnosis of Krabbe disease is based on the demonstration of deficiency of the galactocerebrosidase and identification of the biallelic pathogenic mutations in the GALC gene. The β-galactocerebrosidase activity is measured with a lysate from patient’s white blood cells (WBC) using a liquid chromatography and tandem mass spectrometry (LC-MS/MS) method. This assay is not reliable for detection of gene carriers. Carrier testing can be accomplished through molecular analysis of GALC.
- Blood: 5-10 mL in ACD tube (yellow top) is preferred. Minimum of 3 mL is required. Sodium (or lithium) heparin tubes (green top) or EDTA tubes (lavender top) are also accepted
- 1-2 leukocyte pellets
- Ship whole blood at room temperature; sample must be received within 72 hours of collection
- Ship leukocyte pellet(s) frozen on dry ice
- 7 days