Krabbe Disease

Krabbe disease, also called globoid cell leukodystrophy (GLD), is an incredibly destructive degenerative neurological disorder. The disease most commonly develops within three to six months after birth. Signs that a new born may have this disease are first characterized by

• irritability
• spasms
  
• hypersensitivity to external stimuli
  
• hypertonic fits
  
• loss of reflexes
  

The disease turns fatal normally before two years of age. (1)

GLD has shown itself in individuals after two years of age and causes:

• blindness
  
• weakness in motor/sensory nerves
  
• mental inability
  
• fatality
  

Krabbe disease is an autosomal recessive disorder where the disorder is passed down only if two copies of the abnormal gene are present. The human chromosome fourteen is the one that has been mapped to this neurological disorder. (2)

GLD is distinguished by the disintegration of the protective myelin sheath around nerves, the intrusion of globoid cells which are cells containing more than one nucleus, and eradication of brain cells. Krabbe disease is classified as a leukodystrophy. Leukodystrophys debilitate the maturation of the myelin sheath, the fatty covering around nerve fibers, that provides insulation (2). In the nervous system, myelin is highly important for the quick and precise conduction of impulses (3).

The demylelination of the nervous system causes severe motor skill impairment along with the death of brain cells. An early onset of Krabbe disease causes one to exhibit a change in muscle tone. This change in muscle tone can be observed as a somewhat floppy posture to a more rigid posture called decerebrate posturing. Krabbe disease also causes loss of hearing worsening to the point of deafness.

Those with GLD experience severe seizures at a very young age along with random fevers and vomiting. Just as hearing is affected so is vision as vision loss rapidly turns into blindness. Those experiencing a late onset of this neurological disorder normally experience vision problems first, followed by walking disabilities and muscle rigidity while symptoms vary from person to person (4).

There are several options to test if an individual has Krabbe disease.

• An eye exam focusing on the retina could reveal damage to the optic nerve.

• A blood test looking for low levels of galactosylceramidase (GALC) in white blood cells, which is an essential component of myelin.

• A sample of patient’s cerebrospinal fluid can be tested for an abnormal level of proteins which suggests that there is an abnormal process present in the central nervous system.

• Doctors can use an MRI of the head to further investigate for the presence of GLD.

• check to see if one's nerve conduction velocity is at a normal rate (those with Krabbe disease would show a decrease in conduction velocity for as the myelin sheath breaks down the ease of conduction is decreased) (4).

The treatment for GLD is very limited and most treatments are only to alleviate pain and do not actually correct the deficiency and neurological cause. However, certain treatments have shown to be incredibly effective if treatment is given before the onset of the first symptoms of the disease. There are two different routes that can be taken in order to treat GLD.

• Providing increased GALC activity to available oligodendrocytes in order to get rid of the accumulating psychosine that is inhibiting mylination

• Replace damaged oligodendrocytes by creating new ones out of neural stem cells after increasing GALC activity. (5)
  

Because GLD is such a devastating disease of which treatment is limited and risky, the best way to battle this disease is to prevent it. Those considering having children with a background of Krabbe disease in their family are encouraged to go to genetic counseling before conceiving.

(1) Lee, W. C., Tsoi, Y. K., Trodendle, F. J., DeLucia, M. W., Ahmed, Z., Dicky, C. A., Dickson, D. W., & Eckman, C. B. (2007). Single-dose intracerebroventricular administration of galactocerebrosidase improves survival in a mouse model of globoid cell leukodystrophy. The FASEB Journal, 21. 2520-2527.

(2) Wenger, D. A., Rafi, M. A., & Luzi, P. (1997). Molecular genetics of krabbe disease (globoid cell leukodystrophy): Diagnostic and clinical implications. Human Mutation, 10(4). 268-279.

(3) Michailov, G. V., Sereda, M. W., Brinkmann, B. G., Fischer, T. M., Haug, B., Birchmeier, C., Role, L., Lai, C., Schwab, M. H., & Nave, K. A. (2004). Axonal neuregulin-1 regulates myelin sheath thickness. Science, 304(5671). 700-703.

(4) Fernandes, J., Saudubray, J., Berghe, G., Walter, J.H., & Vanier, M. (2006). Metabolic Diseases: Diagnosis and Treatment. New York, NY: Springer.

(5) Escolar, M. L., Poe, M. D., Provenzale, J. M., Richards, K. C., Allison, J., Wood, S., Wenger, D. A., Pietryga, D., Wall, D., Champagne, M., Morse, R., Krivit, W., & Kurtzberg, J. (2004). Transplantation of umbilical-cord blood in babies with infantile krabbe’s disease. The New England Journal of Medicine, 352(20). 1250-1251.