Krabbe disease is one of a group of genetic disorders called the leukodystrophies. Leukodystrophies are rare inherited neurometabolic disorders resulting from defects in the synthesis or catabolism of myelin. Myelin, which lends its color to the white matter of the brain, is a complex substance made up of at least ten different chemicals. Each of the leukodystrophies affects one of these substances. Krabbe's disease is caused by a deficiency in the lysosomal enzyme galactocerebroside beta-galactosidase (GALC), resulting in accumulation of galactosylceramide within multinucleated macrophages of the white matter, forming globoid cells.
The disorder can be subdivided into three types: the more common infantile form with onset within the first six months; a juvenile form presenting between two and 10 years; and a rarer adult form with onset after 10 years. The infantile form is the most severe, with central demyelination causing irritability, spasticity, ataxia, and seizures. Blindness from optic atrophy, cortical blindness, and deafness may all occur. Peripheral demyelination presents with limb weakness and areflexia. Progressive psychomotor decline results in quadriparesis and death within a few years of onset. Juvenile and adult forms of the disease have a milder phenotype and a slower rate of progression. Symptoms and signs include spasticity, dementia, ataxia, peripheral neuropathy, and loss of vision. Investigations may show milder abnormalities, and nerve conduction can be normal or only mildly affected.