Krabbe Disease
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What is Krabbe disease?
Krabbe disease is a degenerative disorder that affects the nervous system. It is caused by the shortage (deficiency) of an enzyme called galactosylceramidase (GALC). This enzyme deficiency results in defective myelin, the covering that insulates many nerves. Krabbe disease is considered part of a group of disorders known as leukodystrophies, which result from the imperfect growth and development of myelin.
Krabbe disease usually begins before the age of 1 year (early-onset form). Initial signs and symptoms often include feeding difficulties, episodes of unexplained fever, stiff posture, and developmental delay. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and mental retardation. Less commonly, onset can occur in later in childhood, adolescence, or adulthood (late-onset form).
How common is Krabbe disease?
Worldwide, Krabbe disease occurs in about 1 in 100,000 to 200,000 births. A higher incidence (6 cases per 1,000 live births) has been reported in a few isolated communities in Israel.
What genes are related to Krabbe disease?
Mutations in the GALC gene cause Krabbe disease.
Mutations in the GALC gene cause a deficiency of the enzyme galactosylceramidase. This deficiency leads to a progressive loss of myelin that covers many nerves. Without myelin, nerves in the brain and other parts of the body cannot function properly, leading to the signs and symptoms of Krabbe disease.
How do people inherit Krabbe disease?
This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Parents of an individual with this autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
Source: National Institutes of Health
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Studies from University of Illinois, Medical Department yield new information about tissue engineering
2009 JUL 20 - (NewsRx.com) -- According to recent research published in the Journal of Neuroscience, "Lipid rafts (LRs) are membrane realms characterized by high concentrations of cholesterol and sphingolipids. Often, they are portrayed as scaffolds on which many different signaling molecules can assemble their cascades." "The idea of rafts as scaffolds is garnering significant attention as the consequences of LR disruption have been shown to be manifest in multiple signaling pathways. In this study, LRs in the brain of the twitcher (TWI) mouse, a bona-fide model for infant variants of human globoid cell leukodystrophy or Krabbe disease, were investigated. This mouse has deficient activity of GALC (beta-galactosylceramidase) that leads to a progressive accumulation of some galactosyl-sphingolipids in the brain. We hypothesized that the accumulation of psychosine (galactosyl-sphingosine) in the TWI CNS may result in the disruption of rafts in different cell populations such as neurons and oligodendrocytes, both cellular targets during disease. In this communication, we demonstrate that psychosine specifically accumulates in LRs in the TWI brain and sciatic nerve and in samples from brains of human Krabbe patients. It is also shown that this accumulation is accompanied by an increase in cholesterol in these domains and changes in the distribution of the LR markers flotillin-2 and caveolin-1," wrote A.B. White and colleagues, University of Illinois, Medical Department. The researchers concluded: "Finally, we show evidence that this phenomenon may provide a mechanism by which psychosine can exert its known inhibitory effect on protein kinase C. This study provides a previously undescribed biophysical aspect for the mechanism of pathogenesis in Krabbe disease." White and colleagues published their study in the Journal of Neuroscience (Psychosine Accumulates in Membrane Microdomains in the Brain of Krabbe Patients, Disrupting the Raft Architecture. Journal of Neuroscience, 2009;29(19):6068-6077). For additional information, contact E.R. Bongarzone, University of Illinois, College Medical, Dept. of Anatomy & Cell Biology, 808 S Wood St. M-C 512, Chicago, IL 60612, USA. The publisher's contact information for the Journal of Neuroscience is: Society Neuroscience, 11 Dupont Circle, NW, Ste. 500, Washington, DC 20036, USA. Keywords: United States, Chicago, Central Nervous System Disease, Central Nervous System Infection, Enzyme Research, Galactosylceramidase, Globoid Cell Leukodystrophy, Krabbe Disease, Neuroscience, Tissue Engineering, University of Illinois, Medical Department. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2009, Pain & Central Nervous System Week via NewsRx.com.
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