The Symptoms, Diagnosis, and Treatment of Krabbe Disease

Krabbe disease, also known as globoid cell leukodystrophy, is a rare degenerative genetic disease that affects the nervous system. The disease is caused by a mutation in the GALC gene. The resulting enzyme deficiency eventually causes significant damage to the brain and nervous system.

The life expectancy for Krabbe disease varies depending on the age of patient when symptoms start. Adults diagnosed with Krabbe disease can live longer than children diagnosed with the disorder.

This article explains the symptoms of Krabbe disease. It also covers how Krabbe disease is diagnosed and treated.

Symptoms of Krabbe Disease

Krabbe disease is rare. It affects an estimated one in every 100,000 newborns.

There are four subtypes of Krabbe disease, each with their own onset and symptoms.

Since Krabbe disease affects the nerve cells, many of the symptoms it causes are neurological. Type 1, the infantile form, accounts for 85 percent of cases. Type 1 progresses through three stages:

• Stage 1: Begins around three to six months after birth. Affected infants stop developing and become irritable. They have a high muscle tone (muscles are stiff or tense) and trouble feeding.
• Stage 2: More rapid nerve cell damage occurs, leading to loss of use of muscles, increasing muscle tone, arching of the back, and damage to vision. Seizures may begin.
• Stage 3: Infant becomes blind, deaf, unaware of their surroundings, and fixed in a stiff posture. The life expectancy for children with Type 1 is about two years after the start of symptoms, but this can range between eight months to nine years.

The other types of Krabbe disease begin after a period of normal development. These types also progress slower than Type 1 does. The average life expectancy for later onset Krabbe disease is eight years after the start of symptoms. Adults diagnosed with Krabbe disease will have significant neurological impairment, but can live for 30 to 50 years after diagnosis.

Not everyone will see the same symptoms or severity of Krabbe disease. Common symptoms in Type 1 include:

• Excessive crying
• Irritability
• Difficulty feeding
• Unexplained fevers
• Loss of head control
• Hypersensitivity to noise
• Inability to gain weight (failure to thrive)
• Abnormal muscle tightness (spasticity) of the legs

The other types of Krabbe disease may cause these common symptoms:

• Delayed development
• Significant loss of motor function
• Seizures
• Muscle spasticity
• Regression of previously acquired skills
• Vision problems
• Burning pain in the arms and legs

Degeneration in the certain brain tissue can also lead to the following symptoms:

• Legs rigidly extended at the hip and knee
• Arms rotated at the should and extended at the elbow
• Flexed ankles, toes, and fingers (decerebrate rigidity)
• Blindness due to brain cortex degeneration

Other symptoms of Krabbe disease include difficulty swallowing (dysphagia) and peripheral neuropathy. Peripheral neuropathy shows up as muscle weakness, pain, numbness, redness, and burning or tingling sensations in affected areas (especially the arms and legs).

How Krabbe Disease Is Diagnosed

Krabbe disease is caused by a genetic mutation in the GALC gene. This leads to a deficiency in the enzyme galactosylceramidase, an enzyme in white blood cells. To diagnose Krabbe disease, healthcare providers can test blood or skin samples to see if a galactosylceramidase deficiency is present.

A lumbar puncture can be done to sample the cerebrospinal fluid. Abnormally high protein levels can indicate the disease.

For a child to be born with the condition, both parents must carry the mutated gene—located on chromosome 14. If the parents carry the gene, their unborn child can be tested for a galactosylceramidase deficiency through amniocentesis. Some states offer newborn testing for Krabbe disease.

Treatment for Krabbe Disease

The galactosylceramidase deficiency resulting from the genetic mutation leads to a progressive loss of the protective layer covering nerve cells, called myelin. Without this protective layer, our nerves cannot function properly, damaging our brains and our nervous system

There is no cure for Krabbe disease. The standard treatment is hematopoietic stem cell transplantation (HSCT). These stem cells develop into blood cells. Those without symptoms benefit the most from HSCT. Symptomatic patients have mixed results depending on age and progression of the disease and symptoms. HSCT can slow, but not reverse disease progression.

Symptom management may include physical and occupational therapy, depending on the patient's condition. Patients may be advised to avoid antipsychotics, multiple seizure medications, and routine childhood vaccinations. These may accelerate nerve degeneration and disease progression.

Current research is investigating treatments targeting inflammatory markers, enzyme replacement therapy, gene therapy, and neural stem cell transplantation. These therapies are all in their beginning stages and are not yet recruiting for clinical trials.

Summary

Krabbe disease is a rare neurodegenerative disorder resulting in loss of the protective myeline sheath. Although it usually starts between the ages of three to six months, Krabbe disease can also show up later in life, including adulthood.

Symptoms of Krabbe disease include intellectual and behavioral delays, blindness, deafness, facial muscle paralysis, muscle spasms, and seizures. Diagnostic tests look for GALC enzyme activity in white blood cells. Early treatment with hematopoietic stem cell transplantation may be able to slow disease progression.

Talk to your pediatrician or healthcare provider if you are concerned about Krabbe disease.