What is Krabbe Disease?

Krabbe disease is a rare genetic disorder that affects the central and peripheral nervous systems. It is part of a group of disorders known as Leukodystrophy which is characterized by the progressive degeneration of white matter in the brain.  White matter refers to the myelin sheath which is critical for the nervous system to effectively transmit signals that drive our mental and physical ability.

Krabbe disease is also known as globoid cell leukodystrophy or galactosylceramide lipidosis as it is a result of a mutated galactosylceramidase (GALC) gene on chromosome 14. The GALC gene is the code in our DNA that instructs the body to produce a particular enzyme that breaks down certain fats in the brain and kidneys. In Krabbe, as a result of the deficient GALC gene, the body does not have sufficient levels of the enzyme required to break down toxins that damage the myelin sheath. As demyelination occurs, nerves in the brain lose their ability to effectively communicate and symptoms of the disease begin to present themselves.

Krabbe disease is fatal, and symptoms grow progressively worse over the course of the disease. Typically, the earlier the onset of the disease the more quickly it progresses. Children who are diagnosed with the early onset form have an average lifespan of two years. For those diagnosed with late or adult onset Krabbe the disease may progress more slowly, and lifespan can vary significantly.

Krabbe disease is not included in newborn screenings in most states, even though detecting it before symptoms develop could save lives. This is why The Jackson Project collaborates with other organizations to make people aware of supplemental newborn screening and advocate for all states to include Krabbe disease, and other forms of leukodystrophy, into their newborn screenings.

What causes Krabbe Disease?

Krabbe Disease is rare. Research indicates that approximately 1 in every 125 people is a carrier of the disease. Because krabbe disease is inherited in an autosomal recessive manner, it requires that two carriers each pass on the defective gene for a child to be affected. If not, the healthy gene will compensate and allow a carrier to remain disease free. When two carriers have a child they have a 25% chance of both passing on the normal gene, a 50% chance of passing on a normal gene and a mutated gene making the child a carrier, and a 25% chance of passing on two mutated genes resulting in the child being affected by the disease. Krabbe disease occurs in about 1 in every 100,000 births in the United States.

The most common form of Krabbe disease is early-onset, or infantile, where symptoms typically present themselves by six months of age. A less common form is late-onset which develops later in childhood or adolescence. The infantile form of Krabbe disease typically progresses very quickly and is fatal by the age of two, while the later onset form progresses much slower and those affected may live much longer.

How is Krabbe Disease Diagnosed?

If Krabbe disease is not detected through the newborn screening process then it’s often diagnosed once symptoms are displayed outwardly. Diagnosis will likely entail clinical observation of signs and symptoms. A number of diagnostic tests exist, and one or more of them are performed if symptoms observed are consistent with the disease.

A lumbar puncture (spinal tap) may be performed to obtain cerebrospinal fluid protein levels. Elevated protein levels can indicate some sort of abnormal process in the central nervous system.

Brain imaging may be performed by MRI (magnetic resonance imaging) or CT scan (computed tomography). Both can be utilized to produce images that can help identify abnormalities in the brain. Typically, the MRI produces the best image to detect abnormalities that may be associated with Krabbe. An MRI may show increased or decreased signal intensity in white matter in the brain.

Nerve conduction studies can be performed to detect the velocity at which signals travel along the nerve. Due to the destruction of myelin associated with Leukodystrophies, nerve conduction may be at a reduced velocity or display abnormal patterns.

Krabbe disease is caused by a deficiency of the GALC enzyme. A blood or skin sample can be tested to measure GALC enzyme activity. Little or no activity can result in presence of the disease.

Genetic testing can determine particular mutations in our DNA that prevent the body from developing and maintaining healthy myelin.

The above tests will not indicate how quickly the disease will progress. Many mutations of the GALG gene exist, and the specific combination of mutations can cause symptoms and the rate of progression to vary significantly for each case.

Having Krabbe disease screening included as part of the Newborn Screening process allows Krabbe to be diagnosed before symptoms develop. At this point there are possibilities of live-saving procedures.

What are the symptoms of Krabbe Disease?

Just like most other forms of Leukodystrophy, Krabbe Disease is progressive in nature, and symptoms worsen over the course of the diseases. As myelin breaks down, so does signal transmission in the nervous system resulting in a continuous decline in mental and physical ability.  Symptoms that may result are:

• Failure to thrive
• Hearing loss
• Vision loss
• Irritability
• Change in muscle tone (dystonia/hypertonia)
• Seizures
• Loss of speech, slurring
• Inability to eat by mouth
• Change in body movements
• Difficulty breathing
• Change in walking ability
• Swallowing difficulty
• Personality changes

How is Krabbe Disease Treated?

Similar to other Leukodystrophies, there is currently no cure for Krabbe. Treatment is supportive care that is aimed at managing symptoms and maximizing quality of life.

Supportive care may include physical therapy to help maintain flexibility, relieve spasms, and minimize the deterioration of muscle tone. Occupational therapy can assist in achieving as much independence as possible by maintaining a patients current level of function. These therapies can also provide comfort through stretching and proper positioning. Speech therapy focuses on the ability to understand words and the use of them to express oneself. It can also focus on maintaining strength in the lips and tongue to assist with the suck and swallow function necessary to eat and clear saliva.

Medication is another aspect of supportive care that can be used to ease symptoms. This may include medication to control seizures, reduce muscle spasticity and spasms, and reduce reflux.

A range of medical equipment exists such as pediatric wheelchairs and standers that provide postural support that allows patients to achieve a sitting or standing position. Having the ability to bear one’s own weight can aid in proper development of certain parts of the body.

Often times patients receive all or part of their nutritional needs through the use of a gastrostomy tube (g-tube) once they begin losing the ability to eat by mouth. It also aids in the facilitation of medication.

For some types of Leukodystrophy bone marrow, or stem cell, transplants have proved effective when patients are treated prior to being symptomatic. Transplantation of healthy donor cells into patients with these disorders have been shown to halt progression of the disease. Early diagnosis is critical because there is currently no way to repair damage that has already been done.