Krabbe disease

Krabbe disease, also known as globoid cell leukodystrophy or galactosylceramide lipidosis, is a severe inherited neurodegenerative disorder caused by deficiency of the lysosomal enzyme galactosylceramidase (GALC). This enzyme is essential for the breakdown of galactosylceramide and psychosine, which are key components of myelin — the protective insulating sheath surrounding nerve fibers. When GALC is deficient, toxic levels of psychosine accumulate, leading to widespread destruction of myelin-producing cells (oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system). The disease is caused by pathogenic variants in the GALC gene located on chromosome 14q31. The most common form is the infantile (classic) type, which typically presents between 3 and 6 months of age with extreme irritability, feeding difficulties, spasticity, and developmental regression. Affected infants often develop seizures, optic atrophy, peripheral neuropathy, and progressive loss of motor and cognitive function. Without treatment, infantile Krabbe disease is usually fatal by age 2. Later-onset forms (late-infantile, juvenile, and adult) also occur and tend to have a more variable and slower clinical course, presenting with gait abnormalities, vision loss, weakness, and cognitive decline. Krabbe disease primarily affects the central and peripheral nervous systems. Diagnosis is confirmed through measurement of GALC enzyme activity in leukocytes or fibroblasts, supported by genetic testing. Neuroimaging typically shows white matter abnormalities, and nerve conduction studies may reveal peripheral neuropathy. The only disease-modifying treatment currently available is hematopoietic stem cell transplantation (HSCT), which has shown the best outcomes when performed pre-symptomatically in the infantile form, ideally identified through newborn screening. HSCT can slow disease progression but does not cure the condition. Supportive care, including management of spasticity, seizures, feeding difficulties, and pain, remains a critical component of treatment. Gene therapy and substrate reduction approaches are under investigation in clinical research.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Krabbe disease