General description

Krabbe disease, also known as globoid cell leukodystrophy, is a rare autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme galactocerebrosidase. This deficiency damages oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system, leading to demyelination and resulting in both central and peripheral neuropathy. Additionally, accumulation of psychosine, a toxic substrate, contributes to cell damage.

Clinical manifestations

Krabbe disease exhibits considerable clinical heterogeneity, with disease classification based primarily on age of symptom onset. The infantile form represents the most common and severe variant, typically presenting within the first six months of life and characterized by rapid progression leading to death within 2-3 years if untreated. Clinical features of infantile Krabbe disease include severe irritability, feeding difficulties, developmental regression, progressive spasticity, seizures, and eventual loss of motor and cognitive function.

Late-onset forms of Krabbe disease, including juvenile and adult variants, present with more variable clinical courses and generally milder symptoms. Juvenile-onset disease typically manifests between 2-8 years of age with motor dysfunction, cognitive decline, and behavioral changes. Adult-onset forms may present with isolated spastic paraparesis, peripheral neuropathy, or cognitive impairment, often with very slow progression over years to decades.