In most cases, the signs and symptoms of Krabbe disease appear during the first 2 to 5 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
• Muscle 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.

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.

Autosomal recessive inheritance pattern

The gene mutation associated with Krabbe disease only causes the disease if two mutated copies of the gene are inherited. A disease resulting from two mutated copies is called an autosomal recessive disorder.

If each parent has one mutated copy of the gene, the risk for a child would be as follows:

• A 25 percent chance of inheriting two mutated copies, which would result in the disease
• A 50 percent chance of inheriting only one mutated copy, which would result in the child being a carrier of the mutation but would not result in the disease itself
• A 25 percent chance of inheriting two normal copies of the gene

Genetic testing

Genetic testing to understand the risk of having a child with Krabbe disease may be considered in certain situations:

• If one or both parents are likely carriers of a GALC gene mutation because of a known family history of Krabbe disease, a couple may want to have tests to understand the risks in their own family.
• If one child is diagnosed with Krabbe disease, a family may consider genetic tests to identify other children who could develop the disease later in life.
• If the parents are known carriers, they may request a prenatal genetic test to determine if their child is likely to develop the disease.
• Known carriers, who are using in vitro fertilization, may request a genetic test with fertilized eggs before implantation.

Genetic testing should be carefully considered. Ask your doctor about genetic counseling services that can help you understand the benefits, limits and implications of genetic testing.

A number of complications — including infections and respiratory difficulties — can develop in children with advanced Krabbe disease. In the later stages of the disease, children become incapacitated, are confined to their beds and eventually lapse into a vegetative state.

Most children who develop Krabbe disease in infancy die before the age of 2, most often from respiratory failure or complications of immobility and markedly decreased muscle tone. Children who develop the disease later in childhood may have a somewhat longer life expectancy, usually between two and seven years after diagnosis