Krabbe disease

Alternative Names

Krabbe disease, Globoid cell leukodystrophy, Galactosylcerebrosidase deficiency, Galactosylceramidase deficiency

What is Krabbe disease

Krabbe disease is an inherited disorder that affects the central nervous system. About 1 in every 100000 people in the U.S.A suffer from Krabbe disease.

The disease affects muscle tone and movement and can lead to vision and hearing loss. In general, Krabbe disease occurs in babies before 6 months of age, but it can also occur in older children and in adults.

There are 2 forms of Krabbe disease:

• Early-onset Krabbe disease. It develops in the first months of life. Most children with this form die before they reach 2 years old.
• Late-onset Krabbe disease.It starsts in late childhood or early adolescence.

Signs and symptoms

The symptoms that occur in early-onset Krabbe disease may include:

• Changing muscle tone from floppy to rigid (decerebrate posturing)
• Hearing loss that leads to deafness
• Failure to thrive
• Feeding difficulties
• Irritability and sensitivity to loud sounds
• Severe seizures
• Unexplained fevers
• Vision loss that leads to blindness
• Vomiting

The symptoms of late-onset Krabbe disease are:

• Vision problems
• Walking difficulties
• Rigid muscles

Possible complications

At early stage of this disease infections and respiratory difficulties can develop in children. In the later stages of the disease, children become incapacitated, confined to their beds and eventually turn into a vegetative mental state. Most children who have 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 who have the obvious symptoms of the disease later in childhood may have a somewhat longer life expectancy 2-7 years).

What causes

The exact cause of Krabbe disease is a defect in the GALC gene. People who have this gene defect do not make enough of a substance called galactocerebroside beta-galactosidase (galactosylceramidase).

This substance is necessary for our body to make myelin (the material that surrounds and protects nerve fibers). Myelin cannot be produced without it, brain cells die and nerves in the brain and other body areas do not function properly.

Prevention

Genetic counselling is necessary for people with a family history of Krabbe disease who plan to have children.

You should do a blood test in order to identify if you are carrier of the gene defect or not.

Prenatal tests (amniocentesis or chorionic villus sampling) are used to screen a developing baby for this disease.

Treatment

There is no exact treatment for Krabbe disease. It is aimed at reducing symptoms included:

• Anticonvulsant medications to control seizures
• Drugs to ease muscle spasticity and irritability such as benzodiazepines
• Drugs that may reduce the incidence of reflux
• Physical therapy to minimize deterioration of muscle tone
• Occupational therapy so your child may achieve as much independence as possible — for example, by learning such tasks as dressing, eating and brushing teeth on their own.

Bone marrow transplantation

Adult bone marrow is used to replace a child's own bone marrow in Krabbe disease. This procedure is known as hematopoietic stem cell transplantation. It is used in older children who have less-severe forms of the disease or in infants diagnosed at birth.

For other children this treatment is not effective. It cannot slow progression of the disease in babies.

Cord blood transfusion

A transfusion of blood stem cells, obtained from the umbilical cord of unrelated donors, has decreased neurological symptoms in some infants suffering from Krabbe disease.

As an experiment, 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 helped normal development of myelin in these babies. Babies could maintain normal hearing and vision if they were treated before symptoms appeared. Later there was subsequent deterioration in language expression and in motor skills such as walking or picking up objects.