What is Krabbe Disease?
Krabbe disease, also known as globoid cell leukodystrophy, is a rare genetic disorder that affects the central and peripheral nervous systems. It is an autosomal recessive disorder caused by mutations in the
GALC gene, which leads to a deficiency of the enzyme galactocerebrosidase. This deficiency results in the accumulation of psychosine, a toxic substance that damages the myelin sheath of nerve cells.
How is Krabbe Disease Inherited?
Krabbe disease is inherited in an autosomal recessive manner, meaning a child must inherit two copies of the defective gene, one from each parent, to develop the disease. Parents who are carriers of a single defective gene are typically asymptomatic but have a 25% chance of passing the disease to their children with each pregnancy.
Extreme irritability
Feeding difficulties
Developmental delays
Muscle stiffness (hypertonia)
Seizures
In late-onset forms, symptoms may appear during childhood, adolescence, or adulthood and can include progressive muscle weakness, vision loss, and difficulty walking.
How is Krabbe Disease Diagnosed?
Diagnosis of Krabbe disease typically involves a combination of clinical evaluation, imaging studies, and laboratory tests.
Magnetic Resonance Imaging (MRI) can reveal characteristic changes in the brain's white matter. Additionally, enzyme assays measuring galactocerebrosidase activity in leukocytes or fibroblasts and genetic testing to identify mutations in the GALC gene are commonly used to confirm the diagnosis.
What are the Treatment Options?
Currently, there is no cure for Krabbe disease, and treatment focuses on managing symptoms and improving quality of life. Treatment options include:
Supportive care: Physical therapy, occupational therapy, and feeding support can help manage symptoms and improve daily functioning.
Medications: Anticonvulsants may be prescribed to control seizures, and muscle relaxants can help with muscle stiffness.
Hematopoietic stem cell transplantation (HSCT): This procedure, performed early in the disease course, can slow disease progression in some cases, particularly if done before symptoms appear or in the early stages of infantile forms.
What is the Prognosis for Children with Krabbe Disease?
The prognosis for Krabbe disease varies depending on the age of onset and the severity of symptoms. Infants with the early-onset form of the disease typically have a very poor prognosis, with most not surviving beyond two years of age. Those with late-onset forms may have a more variable prognosis, with some individuals living into adolescence or adulthood, albeit with significant neurological impairment.
Are There Any New Research and Developments?
Research into Krabbe disease is ongoing, with scientists exploring potential new treatments and therapies. Gene therapy, which aims to correct the underlying genetic defect, is an area of active investigation. Enzyme replacement therapy, which involves supplementing the deficient enzyme, is another potential treatment under study. Advances in
newborn screening programs may also lead to earlier diagnosis and intervention, improving outcomes for affected children.
How Can Parents Support a Child with Krabbe Disease?
Parents of children with Krabbe disease can provide vital support by working closely with a multidisciplinary medical team to manage symptoms and improve quality of life. Joining support groups and connecting with other families affected by Krabbe disease can also provide emotional support and valuable resources.
