Adult Krabbe disease

Adult Krabbe disease (also known as adult-onset globoid cell leukodystrophy or adult-onset galactosylceramide lipidosis) is a rare, inherited lysosomal storage disorder caused by deficiency of the enzyme galactosylceramidase (GALC). 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-producing cells (oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system). Adult Krabbe disease is the latest-onset form of the condition, typically presenting after age 16 and sometimes not until the third or fourth decade of life. The disease primarily affects the central and peripheral nervous systems. Key clinical features include progressive spastic paraparesis (stiffness and weakness of the legs), peripheral neuropathy, cerebellar ataxia, visual impairment, and cognitive decline. Unlike the rapidly fatal infantile form, adult-onset Krabbe disease tends to progress more slowly, and cognitive function may be relatively preserved early in the course. Some patients present predominantly with motor symptoms such as gait difficulties and spasticity, while others may develop burning paresthesias or loss of fine motor skills. Brain MRI typically shows white matter abnormalities, and nerve conduction studies often reveal a demyelinating peripheral neuropathy. There is currently no cure for adult Krabbe disease. Treatment is primarily supportive and symptomatic, including physical therapy, management of spasticity, and pain control. Hematopoietic stem cell transplantation (HSCT) has shown benefit in presymptomatic or early-symptomatic infantile cases, and it has been explored in adult-onset patients, though evidence for its efficacy in this population remains limited. Enzyme replacement therapy and gene therapy approaches are under investigation. The disease is caused by pathogenic variants in the GALC gene located on chromosome 14q31.

Common questions about Adult Krabbe disease