Krabbe Disease

Krabbe Disease is a lysosomal lipid storage disorder resulting from mutations in the GALC gene encoding galactocerebrosidase. This enzyme normally catalyzes the breakdown of galactocerebroside, a major galactose-containing lipid component of myelin. GALC deficiency leads to accumulation of galactocerebroside and its toxic metabolite psychosine in oligodendrocytes, Schwann cells, and macrophages. Psychosine accumulation is particularly neurotoxic, triggering cell death through multiple pathways including apoptosis, autophagy dysfunction, and oxidative stress. This results in progressive demyelination of both central and peripheral nervous systems. The infantile form, accounting for 90% of Krabbe cases, is the most severe. It typically begins between 3-6 months of age with developmental regression, loss of developmental milestones, progressive spasticity, and loss of visual and hearing function. Without treatment, infantile Krabbe is rapidly progressive and fatal by age 2-4 years. Late-infantile forms show delayed but still progressive neurological decline. Juvenile and adult forms progress more slowly but still cause significant disability. Diagnosis relies on demonstrating reduced GALC enzyme activity in leukocytes or fibroblasts, elevated lyso-galactosylceramide levels, and genetic testing. MRI shows progressive white matter changes and demyelination.