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Definition
Krabbe disease is a rare, inherited, often fatal disorder affecting the central nervous system. The disease can affect muscle tone and movement, and cause vision and hearing loss, among other effects.
In most cases, Krabbe disease develops in babies before six months of age, although it can occur in older children and in adults.
Krabbe disease may be best known in the United States for the media attention it received when former professional football quarterback Jim Kelly raised awareness and research funds for the disorder, which had been diagnosed in his son, Hunter.
Treatment for Krabbe disease mainly involves approaches designed to ease symptoms.
Symptoms
In the more common form of Krabbe disease, which develops in the first months of life, signs and symptoms often include:
- Feeding difficulties
- Failure to thrive
- Fevers
- Vomiting
These babies may also experience:
- Extreme irritability
- Changes in muscle tone (limb and muscle stiffness, poor coordination of movements)
- Seizures
- Progressive loss of hearing and sight
- Spasticity (presence of spasms or consistently increased muscle tone)
- Mental deterioration
Late-onset Krabbe disease
When children have the late-onset form of the disease — which develops later in childhood or in adolescence — they may experience the signs and symptoms above, as well as other signs that may include:
- Visual impairment progressing to blindness, which may be the initial sign
- Difficulty walking (called ataxia or gait disturbances)
- Loss of manual dexterity
As a general rule, the younger the age that Krabbe disease occurs, the more rapid its progression. Some people diagnosed during adolescence may have less-severe symptoms, with muscle weakness as a primary symptom. They may have no impairment of their cognitive abilities.
Causes
Krabbe disease is one of a group of genetic conditions called leukodystrophies. Doctors sometimes refer to Krabbe disease as globoid cell leukodystrophy — the globoid cells are storage cells that play a role in the disorder. The disease is named after the Danish neurologist who first reported infants with the condition in 1916.
The cause of Krabbe disease is a deficiency in an enzyme called galactocerebrosidase (GALC), which is essential for the maintenance of myelin — a fatty substance that insulates your nerve fibers.
A child needs to inherit an abnormal gene from each parent to trigger the disorder. Passing on the genes occurs in an inheritance pattern called autosomal recessive. Specifically, Krabbe disease has been linked to a defect in chromosome 14.
Risk factors
If both parents are carriers of the defective gene for Krabbe disease, their child has a 25 percent risk of developing the disorder. If a child inherits the gene from only one parent, he or she will be a carrier but will never develop symptoms.
Krabbe disease occurs more often in people of Scandinavian descent than in the population at large. The distribution of cases between males and females is approximately equal.
When to seek medical advice
Before you have a baby
If you or your spouse are known to be carriers of the gene abnormality responsible for Krabbe disease — or have extended family members who have developed the disorder — talk with your doctor about undergoing genetic counseling if you're considering pregnancy, in order to better understand the possible risks.
Once your baby is born
If you notice symptoms in your child that could indicate the presence of Krabbe disease — such as seizures or limb stiffness — have him or her evaluated by your doctor. If your doctor suspects Krabbe disease, he or she will refer you to a specialist with expertise in the diagnosis and management of this disorder. That specialist can discuss the available treatment options with you.
Because this condition can progress quickly, it's important to see a doctor promptly when the disease is present.
Tests and diagnosis
Your doctor will conduct a physical exam of your child, evaluating signs and symptoms that may indicate Krabbe disease, and then conduct a number of diagnostic tests.
Your child's doctor will take a blood sample and obtain a skin sample (biopsy), and send both to a laboratory for analysis. There, a lab technician will measure the activity of the GALC enzyme. If GALC activity level is low, your child may have Krabbe disease.
Although the results of these tests can help your doctor make a diagnosis, they don't provide evidence of how quickly the disease may progress. For example, a very low GALC activity level does not necessarily mean that the condition will advance rapidly.
To confirm the diagnosis, your doctor will recommend one or more of the following tests:
- Lumbar puncture (spinal tap). In this test, a needle is inserted into the spinal canal, and a sample of the cerebrospinal fluid around the spinal column is withdrawn. Laboratory tests of this sample can determine the GALC activity level.
- Imaging scans of the brain and head. This may involve a magnetic resonance imaging (MRI) or computerized tomography (CT) scan. An MRI scan uses magnetic signals to create images of the brain; it's the best test to detect any abnormal material in the brain that could be associated with Krabbe disease. Even so, in the early stages of the disease, an MRI can appear normal. A CT scan is a computer-enhanced, high-resolution imaging technique that creates two-dimensional X-ray pictures of the head.
- Nerve conduction studies. These measure the velocity of impulses being sent through the nervous system. This test may involve electrical stimulation of nerves, and then measuring the time it takes the electrical impulse to travel from the stimulation site to the recording device. When myelin is impaired, the nerve conduction is slower.
- Eye examination. This involves a specialist (ophthalmologist) examining the retina, looking for indications of visual deterioration.
- Genetic testing. This may be conducted to detect the genetic mutation or defect associated with Krabbe disease.
Before birth, a fetus can be screened for Krabbe disease. Using a needle, your doctor can withdraw amniotic fluid surrounding the fetus, and then the cells in this fluid can be examined in the lab. A prenatal diagnosis of Krabbe disease can be made by evaluating the activity of GALC enzymes found in these cells.
Complications
A number of complications — including infections and respiratory difficulties — can develop in children whose Krabbe disease has progressed. In the later stages of the disease, children become incapacitated, confined to their beds, and eventually lapse into a vegetative mental state.
Most children who develop Krabbe disease in infancy die before the age of two years old, most often from respiratory failure or complications of immobility and markedly increased muscle tone. Children in whom the disease develops later in childhood may have a somewhat longer life expectancy.
Treatments and drugs
There's no specific, proven treatment for Krabbe disease, nor is there a cure. Krabbe disease treatment is designed primarily to ease symptoms. For example, anticonvulsant medications may be used to manage the seizures associated with this disease. Other drugs may reduce the risk of vomiting.
Some older children with less-severe forms of the disease may benefit from physical therapy, which is intended to minimize deterioration of muscle tone. Some may also benefit from occupational therapy, in which they'll learn to achieve as much independence as possible — for example, learning to dress themselves, brush their teeth and feed themselves.
Some research indicates possible benefits associated with the use of bone marrow transplantation or cord blood transfusion as treatments for Krabbe disease:
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Bone marrow transplantation. Adult bone marrow — the sponge-like material present in bones — has been used to replace a child's own bone marrow in Krabbe disease. This procedure is called hematopoietic stem cell transplantation. It appears to provide benefits primarily to older children who have less-severe forms of the disease, or to infants diagnosed at birth.
For other children — particularly infants who have already developed symptoms — this treatment does not appear to halt or slow progression of the disease in babies, nor has it shown success in a small number of cases in which treatment was carried out in fetuses diagnosed with the disease before birth.
More research — including longer follow-up with more subjects — is needed to better determine the role of this approach and the reasons for its possible benefits. Early research suggests that it may provide functional enzymes to replace those that had been impaired. Clinical trials of hematopoietic stem cell transplantation for presymptomatic, affected infants and older patients with mild symptoms have begun.
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Cord blood transfusion. A transfusion of blood stem cells, obtained from the umbilical cord of unrelated donors, has reduced neurological symptoms in some infants with Krabbe disease.
In small studies, doctors have transfused healthy donor cells with normal enzyme (GALC) activity into babies with Krabbe disease who have not yet developed symptoms. This treatment has stimulated normal development of myelin in these babies. Babies treated within the first two months of life, before symptoms appear, maintained normal hearing and vision, although there was a subsequent deterioration of motor skills such as walking or picking up objects. One study of the use of umbilical cord cells also showed promising findings in fetuses who had been diagnosed prenatally.
This approach may prove to be most appropriate when a suitable transplant donor, such as a family member, is not readily available; matched cord blood may be found more readily.
In the future, gene therapy could play a role in the treatment of Krabbe disease, in which a functional gene is delivered via a virus to the cells or tissue, replacing the abnormal gene that is responsible for the disorder.
Last Updated: 06/12/2007
