Krabbe disease
DEFINITION
Krabbe (KRAH-buh) disease is an inherited disorder that destroys the protective coating (myelin) of nerve cells in the brain and throughout the nervous system.
In most cases, signs and symptoms of Krabbe disease develop in babies before 6 months of age, and the disease usually results in death by age 2. When it develops in older children and adults, the course of the disease can vary greatly.
There’s no cure for Krabbe disease, and treatment focuses on supportive care. However, stem cell transplants have shown some success in infants who are treated before the onset of symptoms and in some older children and adults.
Krabbe disease affects about 1 in 100,000 people in the United States. It is also known as globoid cell leukodystrophy.
CAUSES
Krabbe disease is caused when a person inherits two copies of an altered (mutated) gene — one copy from each parent.
A gene provides a kind of blueprint for producing proteins. If there is an error in this blueprint, then the protein product may not work properly. In the case of Krabbe disease, two mutated copies of a particular gene result in little or no production of an enzyme called galactocerebrosidase (GALC).
Enzymes, such as GALC, are responsible for breaking down certain substances in a cell’s recycling center (lysosome). In Krabbe disease, the short supply of GALC enzymes results in the accumulation of certain types of fats called galactolipids.
Damage to nerve cells
Galactolipids normally exist in cells that produce and maintain the protective coating of nerve cells (myelin). However, an abundance of galactolipids has a toxic effect. Some galactolipids trigger myelin-forming cells to self-destruct.
Other galactolipids are taken up by specialized debris-eating cells in the nervous system called microglia. The process of cleaning up excessive galactolipids transforms these normally helpful cells into abnormal, toxic cells called globoid cells, which promote myelin-damaging inflammation.
The subsequent loss of myelin (demyelination) prevents nerve cells from sending and receiving messages.
SYMPTOMS
In most cases, the signs and symptoms of Krabbe disease appear during the first few months of life. They begin gradually and progressively worsen.
Infants
Common signs and symptoms early in the course of the disease include the following:
- Feeding difficulties
- Unexplained crying
- Extreme irritability
- Fever with no sign of infection
- Declines in alertness
- Delays in typical developmental milestones
- Muscle spasms
- Loss of head control
- Frequent vomiting
As the disease progresses, signs and symptoms become more severe. They may include:
- Seizures
- Loss of developmental abilities
- Progressive loss of hearing and sight
- Rigid, constricted muscles
- Stiff, fixed posture
- Progressive loss of ability to swallow and breathe
Older children and adults
When Krabbe disease develops later in childhood or during adulthood, signs and symptoms can vary widely. They may include:
- Progressive loss of vision
- Difficulty walking (ataxia)
- Decline in thinking skills
- Loss of manual dexterity
- Muscles weakness
As a general rule, the younger the age that Krabbe disease occurs, the faster the disease progresses and the more likely it is to result in death.
Some people diagnosed during adolescence or adulthood may have less severe symptoms, with muscle weakness as a primary condition. They may have no impairment of their thinking skills.
When to see a doctor
The early signs and symptoms of Krabbe disease in infancy can indicate any number of diseases or developmental problems. Therefore, it’s important to get a prompt and accurate diagnosis if your child is experiencing any signs or symptoms of the disease.
Signs and symptoms most often associated with older children and adults also are not specific to Krabbe disease and require a timely diagnosis.
