Krabbe disease

Krabbe disease is an inherited lysosomal storage disorder caused by deficient galactocerebrosidase. Toxic lipid buildup damages myelin and progressively injures the nervous system.

GALC: GALC is the gene encoding galactocerebrosidase, the lysosomal enzyme deficient in Krabbe disease. Pathogenic variants in this gene reduce the enzyme activity that initiates the disease.
Lysosome: A lysosome is a membrane-bound cell compartment that breaks down and recycles biological molecules. Galactocerebrosidase normally performs its lipid-degrading function inside this compartment.
Newborn screening: Newborn screening uses tests shortly after birth to identify conditions for which early intervention can improve outcomes. Screening can identify low GALC activity before symptoms appear, though follow-up is essential.
Infantile Krabbe disease: Infantile Krabbe disease is the early-onset form, usually beginning in the first months of life. It is the most common form and often progresses rapidly after symptoms begin.
Galactocerebrosidase: Galactocerebrosidase is a lysosomal enzyme that breaks down galactolipids, including galactosylceramide. Its deficient activity is the biochemical defect at the start of Krabbe disease.
Sphingolipid: A sphingolipid is a lipid built on a sphingoid backbone and commonly found in cell membranes. Krabbe disease disrupts the breakdown of particular sphingolipids abundant in myelin.
Enzyme assay: An enzyme assay measures the activity of a specific enzyme in a biological sample. Low galactocerebrosidase activity supports diagnosis when interpreted with genetic and biochemical findings.
Late-onset Krabbe disease: Late-onset Krabbe disease begins after infancy and can present during childhood, adolescence, or adulthood. Its slower or variable course contrasts with the typical rapidly progressive infantile form.
Psychosine: Psychosine is a sphingolipid that can disrupt oligodendrocytes and other cells when it accumulates. Its buildup is strongly implicated in the cellular toxicity of Krabbe disease.
Myelin: Myelin is a lipid-rich insulating sheath around many nerve fibers that speeds electrical signaling. Its progressive injury accounts for much of the neurological decline in Krabbe disease.

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