Infantile Krabbe disease

Infantile Krabbe disease, also known as infantile globoid cell leukodystrophy, is a severe, rapidly progressive 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 around nerve fibers. When GALC is deficient, toxic levels of psychosine accumulate, leading to widespread destruction of myelin-forming 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. Infantile Krabbe disease typically presents between 3 and 6 months of age. Affected infants initially appear normal but then develop extreme irritability, feeding difficulties, stiffness (spasticity), and episodes of fever without infection. As the disease progresses, children experience severe developmental regression, loss of previously acquired motor and cognitive milestones, seizures, peripheral neuropathy, optic atrophy leading to blindness, and deafness. A characteristic finding is markedly elevated cerebrospinal fluid protein levels. Brain MRI typically shows progressive white matter abnormalities. The disease follows a devastating course, and without intervention, most affected children do not survive beyond 2 years of age. Currently, there is no cure for infantile Krabbe disease. Hematopoietic stem cell transplantation (HSCT), including umbilical cord blood transplantation, is the only treatment that has shown potential to alter the disease course, but outcomes are significantly better when performed in the pre-symptomatic stage, ideally identified through newborn screening. Once symptoms have developed, HSCT has limited efficacy. Supportive care includes management of spasticity, seizures, feeding difficulties, and pain. Several states in the United States and some countries have implemented newborn screening programs for Krabbe disease to enable early identification and intervention. Gene therapy and substrate reduction approaches are under active investigation in clinical research.

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

Common questions about Infantile Krabbe disease