krabbe+disease

 **Krabbe Disease** or globoid cell leukodystrophy or galactosylceramide lipidosis   **Root cause of disease**  Krabbe disease is a lysosomal storage disorder caused by mutations in the GALC gene located on chromosome 14 (14q31) (NIH).This mutation causes people with the disease to not make enough of the enzyme galactocerebroside beta-galactosidase (galactosylceramidase) which is responsible for making myelin (Cannizzaro, 2008)

C. **Affected cell types/tissues/organs/systems** This autosomal recessive disorder affects white matter in the central and peripheral nervous system. When there is not enough galactosylceramidase, myelin,the material that surrounds and protects nerve fibers break down, brain cells die, and nerves in the brain and other body areas do not work properly (NIH). D. **Historical background** Krabbe disease is named after the Danish physiologist Knud Krabbe who first reported the disease in humans as a ‘familial infantile form of diffuse brain sclerosis’. Others reported it as diffused brain sclerosis or diffuse gliosis. In 1916, Krabbe described five patients who had onset of symptoms at about 5 months of age (Rosenberg, 2008). Symptoms included rigidty of musculature, violent tonic spasms, nystagmus, periodic elevations in temperature, progressive paresis, and early death. In 1924, Collier and Green field used the term globoid to describe the abnormal scavenger cells. Furthermore, Malone and Suzuki reported in 1970 that tissue samples from patients with Krabbe disease could not degrade galactosylceramide.

E. **Common symptoms** include muscle weakness, optic atrophy, spasticity, irritability, deafness, fevers, limb stiffness, seizures, feeding difficulties, vomiting, optic nerve enlargement slowing of mental and motor development, blindness, paralysis, and difficulty when swallowing (Hussain 2011)

F. **Standard treatment** There is currently no cure for this disease. Treatment at this time is limited to stem cell transplantation in infants that have not shown symptoms yet as well as mildly affected on set patients (Rosenberg, 2008)

G. **Current research:** (The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), conducts research on the lipid storage diseases in laboratories at the NIH (NIH). Furthermore, a recent study in the New England Journal of Medicine reports that cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear (Escolar et al., 2005). In addition, Potter and colleagues believe that early demise in Krabbe disease is due to mechanisms other than myelin loss. In fact, their data reveal that neuroinflammation plays a huge role in the progression of this disease (Potter et al., 2013).

H. **References:** Cannizzaro, L. A., Chen, Y. Q., Rafi, M. A., & Wenger, D. A. (2008). Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization. //Cytogenetic and Genome Research//, //66//(4), 244-245. Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J (2005). [|"Transplantation of Umbilical-Cord Blood in Babies with Infantile Krabbe's Disease"] <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">. //<span style="font-family: 'Times New Roman','serif'; font-size: 16px;">New England Journal of Medicine //<span style="font-family: 'Times New Roman','serif'; font-size: 16px;"> **352** (20): 2069–2081. <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Hussain, S. A.; Zimmerman, H. H.; Abdul-Rahman, O. A.; Hussaini, S. M.; Parker, C. C.; Khan, M. (May 2011). "Optic Nerve Enlargement in Krabbe Disease: A Pathophysiologic and Clinical Perspective". Journal of Child Neurology 26 (5): 642–644.
 * || <span style="font-family: 'Times New Roman','serif'; font-size: 16px;">Potter, G. B., Santos, M., Davisson, M. T., Rowitch, D. H., Marks, D. L., Bongarzone, E. R., & Petryniak, M. A. (2013). Missense mutation in mouse GALC mimics human gene defect and offers new insights into Krabbe disease. //Human molecular genetics//.

<span style="font-family: 'Times New Roman','serif';">http://www.nlm.nih.gov/medlineplus/ency/article/001198.htm ||