Late-infantile/juvenile Krabbe disease

Late-infantile/juvenile Krabbe disease (also known as late-onset Krabbe disease or late-onset globoid cell leukodystrophy) is a rare inherited lysosomal storage disorder caused by deficiency of the enzyme galactosylceramidase (GALC), encoded by the GALC gene on chromosome 14q31. This enzyme is essential for the breakdown of galactosylceramide and psychosine, which are key components of myelin in the nervous system. When GALC is deficient, these toxic substrates accumulate, leading to progressive destruction of myelin (demyelination) in both the central and peripheral nervous systems. Unlike the more severe infantile form, late-infantile/juvenile Krabbe disease has a later onset, typically between 6 months and 16 years of age, and generally follows a slower but still progressive course. Key symptoms include progressive motor difficulties such as spasticity, gait abnormalities, and loss of previously acquired motor skills. Children may develop vision problems (including optic atrophy), peripheral neuropathy with weakness and decreased reflexes, cognitive decline, and seizures. Irritability and behavioral changes may be early features, particularly in younger children. As the disease progresses, patients may lose the ability to walk, speak, and perform daily activities independently. Nerve conduction studies typically show slowed velocities consistent with peripheral neuropathy, and brain MRI reveals characteristic white matter abnormalities. There is currently no cure for late-infantile/juvenile Krabbe disease. Hematopoietic stem cell transplantation (HSCT) is the primary disease-modifying treatment and has shown the best outcomes when performed early in the disease course, before significant neurological deterioration has occurred. HSCT can stabilize or slow disease progression in some patients, particularly those identified presymptomatically or in early stages. Supportive care includes physical therapy, occupational therapy, management of spasticity, seizure control, nutritional support, and palliative measures to maintain quality of life. Gene therapy and substrate reduction approaches are under investigation in clinical research settings.

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