Clinical Information

Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive lysosomal storage disorder caused by an enzyme deficiency of galactocerebrosidase (GALC). Krabbe disease is caused by mutations in the GALC gene, and it has an estimated frequency of 1 in 100,000 births.

Eighty-five to ninety percent of patients present before the first year of life with central nervous system impairment including increasing irritability, developmental delay, and sensitivity to stimuli. Rapid neurodegeneration including white matter disease follows with death usually occurring by age 2. Ten to 15 percent of individuals have late onset forms of the disease that are characterized by ataxia, vision loss, weakness, and psychomotor regression presenting anytime from age 6 months to the seventh decade of life. The clinical course of Krabbe disease can be variable, even within the same family. Treatment is mostly supportive, although hematopoietic stem cell transplantation has shown some success if treatment begins before neurologic damage has occurred.

Psychosine (PSY), a neurotoxin at elevated concentrations, is 1 of 4 substrates degraded by galactocerebrosidase. It has been shown to be elevated in patients with active disease and therefore, may be a useful biomarker for the presence of disease or disease progression. PSY measurement in dried blood spots is under study to determine if it is a useful follow-up to an abnormal newborn screen for Krabbe disease.

Reduced or absent galactocerebrosidase in leukocytes (CBGC / Galactocerebrosidase, Leukocytes) or fibroblasts (CBGT / Galactocerebrosidase, Fibroblasts) along with psychosine analysis can indicate a diagnosis of Krabbe disease. Molecular sequencing of the GALC gene (KRABZ / Krabbe Disease, Full Gene Analysis and Large [30 kb] Deletion, PCR) allows for detection of the disease-causing mutations in affected patients and carrier detection in family members.