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Krabbe Disease
Sunday, 15 June 2003
Thursday, 25 August 2005
Globoid Cell Leukodystrophy

What

Krabbe Disease (KD) is a rare degenerative disorder of the nervous system. Krabbe disease affects the myelin sheath, which is a fatty covering that acts as an insulator on nerve fibers. Myelin is essential for the transmission of signals in the nervous system. In KD there is severe loss of the myelin sheath and presence of globoid bodies, which are large, irregular cells found in and around blood vessels in the brain. There are two forms of the disease: infantile onset which makes up the majority (85-90%) of cases, and late onset which can occur in childhood, adolescence or even adulthood.

Who

Krabbe Disease is a very rare autosomal recessive disorder. Affected children must inherit two copies of the dysfunctional gene – one from each parent. The occurrence in the U.S. is 1 in 100,000 live births. The disease affects all races and both males and females equally. Most commonly, Krabbe Disease develops in early infancy around 3-6 months of life.

Signs and Symptoms

About 85-90% of individuals with Krabbe Disease have the early onset infantile form of the disease. In this form, symptoms usually occur around 3-6 months of life. There are typically three stages to the early onset infantile form of Krabbe Disease, and children with this disease may have the following symptoms at each stage: Stage I is characterized by irritability and hypersensitivity to sound, fevers without any signs of infection, vomiting and weight loss, stiffness, and arrested development. In Stage II, infants may rapidly lose previously attained skills, become increasingly stiff with hyperactive reflexes, and may develop seizures. Stage III is characterized by blindness, deafness and no voluntary movement. Stage III may be reached within a few weeks or after several months of symptoms. Severely affected infants usually die from infections or respiratory failure by 13 months of age, although some may live for two or more years.

Possible Causes

KD is an autosomal recessive disease, meaning affected infants must inherit two copies of the defective gene – one from each parent. The affected gene is referred to as GALC, located on chromosome 14, and makes an enzyme called galatocerebrosidase. In KD, the defective gene does not produce this enzyme and there is an increase in the destruction of myelin, and the accumulation of a protein called galactoceramide in the brain. The increased destruction of myelin causes severe loss of the myelin sheath, and the accumulation of galactoceramide causes the presence of globoid bodies in the brain.

Diagnosis

There are several tests that can be used to diagnose Krabbe Disease. The first test that a physician may order is an MRI brain scan. The MRI may show evidence of brain atrophy (wasting) and problems with the myelin (sometimes called the white matter). To look specifically for Krabbe disease, a blood test can be done to measure the amount of galactocerebrosidase (GALC) activity. If the child has 0-5% of the average GALC activity in the white blood cells, then the child can be diagnosed with Krabbe Disease. It is also possible to perform molecular genetic testing as a method of diagnosis. A specific 30 kb deletion of the GALC gene is often found in individuals with infantile onset Krabbe Disease. This deletion can be tested for by mutation analysis. This test will detect 35% - 45% of affected individuals. Because this gene test is not very sensitive, it is not used for the primary diagnosis, but may identify carriers in families with known mutations and may be used for prenatal diagnosis.

Treatment

Currently, there is no treatment available for this disease. However, individuals with infantile onset Krabbe disease, who are identified prior to the onset of symptoms, may be candidates for bone marrow transplant or umbilical cord blood stem cell transplant which will replace the missing enzyme and may slow or stop the progression of the disease.

Prognosis

The prognosis for children with Krabbe Disease is not very good. Most children with the early onset infantile form do not survive past the age of 3 years. There is hope that with early identification, affected individuals may undergo bone marrow or umbilical cord blood stem cell transplant, but usually the disease progresses too quickly to make this option possible. Scientists are working on gene therapy and more sophisticated stem cell therapy for this disease, but at this time, they are only at the theoretical stage clinically.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

Krabbe's Family Network
A great website with information about the disease and support for those affected by it.

NINDS Krabbe Disease Information Page
An easy to read article on Krabbe Disease with additional resources provided.

Gene Reviews
A very detailed article on Krabbe's disease with nice definitions of medical and genetics terms.

Krabbe Disease Homepage
A nice website with personal stories of those affected by the disease.

Google Search for Krabbe Disease

References and Sources

www.ninds.nih.gov/health_and_medical/disorders/krabbe_doc.htm www.geneclinics.org/profiles/krabbe/ home.mdconsult.com/das/book/28973377/view/873/1540.html/top