Krabbe disease is a rare genetic disorder of the nervous system that usually results in death.
People with Krabbe disease have a deficiency of galactosylceramidase production, which results in extensive degeneration of the myelin sheaths surrounding nerves in the brain.
Without this myelin protection, cells in the brain will degenerate, and the body’s nervous system won’t work properly.
About 85 to 90 percent of Krabbe disease cases begin in infancy (onset by age 6 months), but it can also develop later in life.
There’s currently no cure for Krabbe disease, and most infants with this disease will die before age 2.
Krabbe disease is also known by the following names:
- galactocerebrosidase (GALC) deficiency
- galactocerebroside beta-galactosidase deficiency
- galactosylceramidase deficiency
- galactosylceramide lipidosis
- globoid cell leukoencephalopathy
- Krabbe’s disease
- leukodystrophy, globoid cell
- sphingolipidosis, Krabbe’s type
The symptoms and severity of Krabbe disease vary.
In general, the earlier the age of onset of Krabbe disease, the faster the disease will progress. People who develop Krabbe disease later in life may have less severe symptoms than infants who get the disease.
Early onset Krabbe disease
Infants with the disease may experience:
- excessive irritability
- difficulty swallowing
- unexplained fevers
- partial unconsciousness.
They may also be hypersensitive to sounds and therefore easily startled.
Problems with the limbs may also surface, including spastic contractions in the lower extremities and seizures. The legs are sometimes rigidly extended at the hip and knee. The ankles, toes, and fingers may be flexed.
Blindness and slow mental and physical development may also occur, as well as peripheral neuropathy. Peripheral neuropathy is a condition characterized by:
- muscle weakness
- burning or tingling sensations
Late onset Krabbe disease
Symptoms of late onset Krabbe disease in older children and adolescents include:
- lack of control of voluntary movements
- progressive vision loss
- progressive rigidity of muscles in the legs
Krabbe disease is caused by a genetic mutation — a permanent change in the DNA sequence that makes up a certain gene. The mutation affects the product that the gene codes for.
The gene for Krabbe disease can be found on chromosome 14. A child needs to inherit the abnormal gene from both parents to develop the disease. The abnormal gene results in a shortage of an important enzyme that your body needs called galactosylceramidase (GALC).
However, late onset cases have a slightly different gene mutation.
GALC is an enzyme that breaks down galactosylceremide and psychosine molecules in the brain. Krabbe disease patients can have psychosine levels that are 100 times higher than those who don’t have the disease.
Krabbe disease is very rare. It affects about 1 in every 100,000 people in the United States and occurs most frequently in people of Scandinavian descent. Men are affected as often as women.
A child has a one in four chance of inheriting two copies of the defective gene and therefore developing the disorder if both parents have the defective gene.
Your doctor will conduct a physical exam to look for symptoms. The doctor will take a sample of blood or skin tissue biopsy and send it to a laboratory for analysis.
The laboratory can test for GALC enzyme activity in the sample. If GALC activity levels are very low, the child may have Krabbe disease. The following tests may also be performed to confirm a diagnosis:
- Imaging scans (MRI). A doctor can use an MRI of the brain to look for abnormalities, which will show diffuse demyelination in children with this disease.
- Nerve conduction studies. These studies measure the speed at which electrical impulses are sent through the nervous system
- Eye examination. This examination looks for signs of damage to the optic nerve.
- Genetic testing. Genetic testing can detect the genetic defect that causes Krabbe disease.
- Amniocentesis. A diagnosis can also be made with amniocentesis prior to a child’s birth.
Palliative and supportive care are the only treatments available for most cases of Krabbe disease.
However, patients who are diagnosed before symptoms begin or in cases of later onset may be treated with a hematopoietic stem cell transplant (HSCT).
The transplant may stabilize the disease progression and extend the life of the treated person.
Bone marrow transplantation and stem cell therapy have been used in a small number of people with the disease. And gene therapy is also a treatment used in experimental trials.
The disease is usually life threatening. Since it damages a person’s central nervous system, complications include:
- severe loss of muscle tone
- severe mental deterioration
- respiratory failure and death
On average, infants who develop Krabbe disease will die before age 2. Children who develop the disease later in life will live a bit longer, but typically die between 2 and 7 years after they’re diagnosed.
If both parents carry the genetic defect that causes Krabbe disease, there’s a 25 percent chance that the child will inherit two copies of the defective gene and therefore have the disease.
The only way to avoid the risk is if the carriers decide to not have children. The parents can find out if they carry the gene for Krabbe disease through a blood test, and this is a good idea especially if the disease runs in the family.
If there’s a family history of Krabbe disease, prenatal tests can screen the fetus for the condition. Genetic counseling is recommended for people with a family history of Krabbe disease if they’re considering having children.