Krabbe Disease

The enzyme galactosylceramide beta-galactosidase (GALC) breaks down several important compounds in the body. In Krabbe disease, there isn’t enough GALC available, and substances which should be broken down start to accumulate. The build-up of these substances damages the nerve cells in the central nervous system, destroying many of them and preventing the repair of others.

It is estimated that Krabbe disease affects 1 in 100,000 people worldwide, with higher incidences reported in some areas. It affects people of all ethnic backgrounds.

Four subtypes
Krabbe disease is divided into four subtypes based on when the disease begins:

• Type 1 – Infantile: begins at age 3 – 6 months
• Type 2 – Late infantile: begins at age 6 months – 3 years
• Type 3 – Juvenile: begins at age 3 – 8 years
• Type 4 – Adult onset: begins any time after 8 years of age

Symptoms
Since Krabbe disease affects the nerve cells, the symptoms it causes are neurological. Type 1, the infantile form, accounts for 85-90% of known cases. It progresses through three stages:

• Stage 1 begins around age 3 – 6 months. The infant stops developing and becomes irritable and has high muscle tone (muscles are stiff or tense). The infant has trouble feeding.
• Stage 2 brings more rapid nerve cell damage, leading to loss of use of muscles, increasing muscle tone, arching of the back, and damage to vision. Seizures may begin.
• Stage 3 is the end stage, in which the infant becomes blind, deaf, unaware of his surroundings, and fixed in a stiff posture. The average lifespan in Type 1 Krabbe disease is 13 months.

Type 2, 3, and 4 Krabbe disease begin after a period of normal development. These types progress more slowly than Type 1. Children generally do not survive beyond two years after Type 2 begins, but in Types 3 and 4 the lifespan reduction may vary, and the symptoms may not be as severe.

Diagnosis
If the symptoms suggest Krabbe disease, a blood test can be done to see if the child or adult has GALC deficiency, which would confirm the diagnosis. A lumbar puncture can be done to sample the cerebrospinal fluid, which in Krabbe disease has abnormally high levels of protein. The test for GALC deficiency can also be done on an unborn child if the parents carry the defective gene (on chromosome 14).

Treatment
There is at present no way to stop Krabbe disease or cure it once it is in full swing. However, if an individual is diagnosed before symptoms begin, or symptoms start later in life and progress slowly, it is possible to use bone marrow or stem cell transplantation as treatment. The transplant adds normally-functioning cells which can produce GALC.

Several areas of research could help Krabbe disease
Researchers are investigating therapy which replaces the missing GALC. They are also looking at gene therapy, in which a normally-functioning gene would take the place of the defective gene that causes the disease. In addition, people with Krabbe disease would benefit from stem cell research, in which scientists would attempt to grow new nerve cells for the brain.

Information for this article was taken from:
Tegay, D. H. (2002). Krabbe disease. eMedicine, accessed at http://www.emedicine.com/ped/topic2892.htm