|| Krabbé disease is a rare and fatal, inherited degenerative disorder of the central and peripheral nervous systems. It is characterized by the breakdown of the nerve’s protective myelin coating, and destruction of brain cells. Krabbé disease is one of 34 genetic disorders called the leukodystrophies. These disorders impair the growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers, and cause severe degeneration of mental and motor skills. Myelin, which lends its color to the “white matter” of the brain, is a complex substance made up of at least 10 different enzymes. Each of the leukodystrophies affects one (and only one) of these substances. Krabbé disease is caused by a deficiency of galactocerebrosidase (GALC), an essential enzyme for myelin metabolism.|
Without myelin, nerves in the brain and other parts of the body cannot function properly. This loss of myelin further leads to muscle weakness and paralysis, affecting the infant's ability to move, swallow, and breathe. The disease most often affects infants, with onset before age 6 months, but can occur in adolescence or adulthood. Initially these babies appear to develop normally and will reach milestones before they regress. Symptoms include irritability, unexplained fever, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. Other symptoms include muscle weakness, spasticity, deafness, and blindness. The average age of death in individuals with the infantile form is 13 months; however, some succumb by eight months of age. Others live for two or more years. Even with the best of care, death usually results from infections and respiratory failure caused by progressive paralysis.
Krabbe disease is inherited in an autosomal recessive manner. When two parents carry a disease-causing mutation in the GALC gene there is a one-in-four chance that any child they have will inherit a Krabbe gene from each parent and have the disease. There is a one-in-four chance that the child will inherit the normal gene from each parent and be completely free of the disease and the Krabbe gene. There is a two-in-four chance that the child will inherit one of each kind of gene and be a carrier like the parents and free of disease. If only one parent is a carrier, none of their children can have the disease, but each child has a 50-50 chance of inheriting the Krabbe gene and being a carrier.
This genetic disease is found in all ethnic groups. The carrier rate in the general population is estimated to be 1 in 125. Krabbe Disease occurs in about 1 in 100,000 births in the United States.
What treatment is available?
There is no cure for Krabbe disease. Treatment is symptomatic and supportive. Affected children can only be made as comfortable as possible. However, results of a very small clinical trial of patients with infantile Krabbé disease found that children who received umbilical cord blood stem cells from unrelated donors prior to symptom onset developed with little neurological impairment. It appears that stem cell transplants may slow or even arrest the progression of the disease process. There is no evidence yet that stem cells can reverse damage that has already occurred. Therefore, this method appears to be of some benefit in cases of later onset or in infantile patients who have been diagnosed before or at birth. It does not appear to be beneficial in the case of infantile patients who have already begun displaying the symptoms of Krabbe Disease.