Krabbe Disease
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Introduction to Krabbe Disease
Krabbe disease belongs to a family of disorders identified as lysosomal storage diseases. This disorder is characterized by the lysosomal accumulation of galactosylceramides as a consequence of defects in the lysosomal hydrolase, galactosylceramidase. Galactosylceramides are almost exclusively found in the myelin sheaths of nerve cells. Thus, defects in their metabolism lead to the severe neurologic involvement of Krabbe disease.
A Galactosylceramide (galactocerebroside)
The galactosylceramidase gene, formally identified as galactocerebroside β-galactosidase (symbol GALC), is found on chromosome 14q23.3–32.1 spanning 56 kb and composed of 17 exons encoding a 669 amino acid glycoprotein. At least 60 different mutations have been identified in the GALC gene resulting in Krabbe disease. Transmission of Krabbe disease occurs as an autosomal recessive trait.
Clinical Features of Krabbe Disease
Because a characteristic feature of Krabbe disease is the accumulation of multinucleated globoid cells in the white matter of the brain, the disease is also know as infantile globoid cell leukodystrophy (GLD). This disease is a rapidly progressing disease that is invariably fatal before the end of the second year. There is an adult onset form of the disease that is characterized by blindness, dementia and spastic paraparesis.
Symptoms of the infantile form manifest around 3 to 6 months of age. Clinical manifestation of Krabbe disease is limited to the nervous system. In addition to the presence of the hematogenous globoid cells of macrophage lineage, there is near total loss of myelin and oligodendroglia as well as astrocytic gliosis. The earliest signs of Krabbe disease are hypersensitivity to external stimuli. The disease rapidly progresses to severe psycho-motor deterioration. Infants become decerebrate, are blind and usually deaf, and have no contact with their surroundings. There is no treatment for the infantile form of Krabbe disease. Bone marrow transplantation has been effective in patients with minimal neurologic involvement.
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Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu