Krabbe disease

Krabbe disease is a rare and often fatal inherited disorder of lipid metabolism that progressively destroys the protective myelin coating around nerve fibers in the brain and peripheral nervous system. It is caused by mutations in the GALC gene on chromosome 14, inherited in an autosomal recessive pattern, which leave the body unable to produce enough of the enzyme galactosylceramidase; without this enzyme, toxic lipid byproducts accumulate inside cells and damage the tissue that produces and maintains myelin. In the most common, infantile-onset form, previously healthy babies develop irritability, feeding difficulties, seizures and rapid developmental regression, and the large majority of these infants die before the age of two. Later-onset forms progress more slowly and can present instead with muscle weakness, vision loss and sensory disturbances beginning in childhood, adolescence or even adulthood. Diagnosis is made by measuring galactosylceramidase enzyme activity in blood, confirming the finding with genetic testing for GALC mutations, and, when needed, examining brain tissue for the disease's characteristic globoid cells. There is no cure, though hematopoietic stem cell transplantation performed before symptoms begin has been shown to slow progression in some cases; otherwise care is supportive, including feeding tubes and physical therapy, while gene therapy remains under clinical investigation.