Krabbe disease (KRAH-bay disease) is an inherited, often fatal disorder affecting the central nervous system. Krabbe disease affects about 1 in every 100,000 people in the United States. The disease affects muscle tone and movement, and may cause vision and hearing loss, among other devastating effects. In most cases, Krabbe disease develops in babies before 6 months of age, although it can occur in older children and in adults. There's no cure for Krabbe disease and treatment mainly involves approaches designed to ease symptoms. However, early studies using stem cell transplants to treat Krabbe disease before symptoms begin have had some success.

Complications of Krabbe’s disease

• 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 2 years old, most often from respiratory failure or complications of immobility and markedly decreased muscle tone. Children in whom the disease develops later in childhood may have a somewhat longer life expectancy, usually between two and seven years after diagnosis.

Causes of Krabbe’s disease

• Krabbe disease is caused by a genetic defect that results in a deficiency in an enzyme called galactocerebrosidase (GALC). This enzyme is essential for the maintenance of myelin — a fatty substance that insulates your nerve fibers.
• Doctors sometimes refer to Krabbe disease as globoid cell leukodystrophy. Globoid cells store molecules called galactolipids. Without GALC, galactolipids accumulate in the brain. Psychosine is a type of galactolipid, and it's the one suspected of causing the most damage in Krabbe disease. The damage occurs because when psychosine levels are high, the cells that produce myelin begin to self-destruct.
• A child needs to inherit an abnormal gene from each parent to trigger the disorder. This inheritance pattern is called autosomal recessive. The gene for Krabbe disease is located on chromosome 14.

Signs & Symptoms of Krabbe’s disease

Early-onset Krabbe disease

In the more common form of Krabbe disease, which develops in the first months of life, signs and symptoms often include:

• Feeding difficulties
• Unexplained crying
• Loss of head control
• Fevers
• Vomiting
• 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)
• Loss of developmental milestones

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 faster it progresses. Some people diagnosed during adolescence or adulthood may have less-severe symptoms, with muscle weakness as a primary symptom. They may have no impairment of their cognitive abilities.

Diagnosis of Krabbe’s disease

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 finding doesn't always mean that the condition will advance rapidly.

To confirm the diagnosis, your doctor will recommend one or more of the following tests:

• 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 abnormality 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. A doctor who specializes in eye care (ophthalmologist) examines 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. To do this, your doctor withdraws amniotic fluid surrounding the fetus using a needle, 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 or by genetic mutation analysis.

Treatments of Krabbe’s disease

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 incidence 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:

• 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 hasn't been successful. It doesn't appear to halt or slow progression of the disease in babies, nor has it been effective in treating fetuses diagnosed with the disease before birth. More research — including longer follow-up with more subjects — is needed to better assess the possible benefits of this treatment.
• 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 before symptoms appear seemed to maintain normal hearing and vision; however, there were subsequent deterioration in language expression and in motor skills, such as walking or picking up objects. 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.

Prevention of Krabbe’s disease

Prepregnancy screening

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.

Newborn screening

Because stem cell transplants may delay the onset of Krabbe disease when given before symptoms begin, screening newborns may become more important. New York State has already adopted universal newborn screening for Krabbe disease and Illinois plans to do so by 2010. Even when transplant isn't feasible, screenings allow for early detection, which can help improve an infant's quality of life by intervening with supportive care earlier. If you don't live in a state where screening is commonplace and you have a family history of Krabbe disease, talk with your doctor about having your newborn screened.

When to seek Medical Advice

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 if you suspect the disease is present.