Krabbe Disease (Globoid Cell Leukodystrophy) – Causes and Treatment.


Krabbe disease is an inherited disorder characterized by progressive muscle weakness and stiffness, feeding problems, slowed mental and physical development, vision loss, and seizures. It involves the deficiency in the enzyme galactocerebrosidase (GALC), which is important in the growth and maintenance of myelin, the protective covering around the nerve cells. The symptoms of crab disease are due to the abnormal breakdown of myelin and build-up of toxic by-products in the body. Krabbe disease is also known as galactocerebrosidase deficiency and globoid cell leukodystrophy.


Overall calculated European incidence is 1 case per 100,000 populations, with a higher reported incidence in Sweden of 1.9 cases per 100,000 populations. An unusually high incidence, 6 cases per 1000 live births, is reported in the Druze community in Israel.


Early Infantile Krabbe Disease (EIKD)

The Early Infantile form of Krabbe Disease is the most severe. Initially, it is often misdiagnosed as colic, reflux, food/milk allergy, or even Cerebral Palsy. Within the first few months of life, affected babies begin to show symptoms such as extreme irritability, feeding difficulty, stiffness, and loss of or unmet developmental milestones.

Some symptoms include, but are not limited to: extreme irritability, excessive crying, stiffness, decline of motor skills, loss of previously attained milestones, difficulty feeding, weight loss, seizures, rapid involuntary movement of the eyes (nystagmus), muscle spasms in the arms and legs (clonus), and arching of the back.

Later Onset Infantile Krabbe Disease

Children with Late Infantile Krabbe Disease begin to show symptoms between 6 months and 3 years of age. Symptoms are similar to those described for Early Infantile Krabbe Disease.

Some symptoms include, but are not limited to: extreme irritability, excessive crying, stiffness, decline of motor skills, loss of previously attained milestones, difficulty feeding, weight loss, seizures, rapid involuntary movement of the eyes (nystagmus), muscle spasms in the arms and legs (clonus), and arching of the back.

Adolescent-Onset Krabbe Disease and Adult Onset Krabbe Disease

Those with Adolescent Krabbe Disease typically show an initial regression of motor skills at 3 years of age or later. After the initial decline, the disease typically progresses more slowly than the infantile-onset, often over a period of several years.

The adult onset of Krabbe Disease frequently begins with vision problems, generally followed by muscle stiffness and difficulty walking. It is possible that those with this form of Krabbe can be misdiagnosed with diseases such as Multiple Sclerosis.

Some symptoms include, but are not limited to progressive loss of vision, change in gait or difficulty walking (ataxia), loss of manual dexterity, muscle weakness, and pain.

Risk factors

The gene mutation which is linked with Krabbe disease only causes the disease when two mutated copies of the gene are inherited. When a disease results from two mutated copies it is called an autosomal recessive disorder. If each parent has one mutated copy of the gene, the child’s risk will be as follows:

  • 25 percent chance of inheriting two mutated copies, resulting into the disease
  • 50 percent chance of inheriting only one mutated copy, which means that the child will carry the mutation but it will not result in the disease itself
  • 25 percent chance of inheriting two normal copies of the gene

Causes of krabbe disease

The condition occurs when a person inherits two copies of an altered gene, one copy from each parent. A gene gives a kind of blueprint for producing proteins. But when there is an error in this blueprint, the protein product may not work properly. In this condition, two mutated copies of a particular gene lead to little or no production of an enzyme called galactocerebrosidase.


The majority of cases of Krabbe Disease appear within the first year of life. The patients rapidly regress to a condition with little to no brain function, and generally die by age 2, though some have lived longer. Death generally occurs as a result of a respiratory infection or brain fever. Symptoms that might be encountered in the infantile form of Krabbe Disease include:

  • Developmental delay
  • Seizures
  • Limb stiffness
  • Optic atrophy: wasting a muscle of the eye, resulting in vision difficulties
  • Neurosensory deafness
  • Extreme irritability
  • Spasticity: the presence of spasms
  • Ataxia: loss of the ability to control muscular movement
  • Progressive psychomotor decline: a progressive decline in the coordination of movement

Although the majority of Krabbe Disease patients show symptoms within the first year of life, there have been cases diagnosed at all ages, through late adulthood. In general, the earlier the diagnosis, the more rapid the progression of the disease.

A child with Krabbe disease

Those who first show symptoms at ages 2-14 will regress and become severely incapacitated, and generally die 2-7 years following diagnosis. Some patients who have been diagnosed in the adolescent and adult years have symptoms that remain confined to weakness without any intellectual deterioration, while others may become bedridden and deteriorate both mentally and physically.

Complications of krabbe disease

The disease is usually life-threatening. Since it damages a person’s central nervous system, complications include:

  • Blindness
  • Deafness
  • Severe loss of muscle tone
  • Severe mental deterioration
  • Respiratory failure and death

Diagnosis and test

If Krabbe disease is not detected in the newborn screening process then it’s often diagnosed once symptoms are displayed outwardly. Diagnosis will likely entail clinical observation of signs and symptoms. A number of diagnostic tests exist, and one or more of them are performed if symptoms observed are consistent with the disease.

A lumbar puncture (spinal tap) may be performed to obtain cerebrospinal fluid protein levels. Elevated protein levels can indicate some sort of abnormal process in the central nervous system.

Brain imaging may be performed by MRI (magnetic resonance imaging) or CT scan (computed tomography). Both can be utilized to produce images that can help identify abnormalities in the brain. Typically, the MRI produces the best image to detect abnormalities that may be associated with Krabbe. An MRI may show increased or decreased signal intensity in white matter in the brain.

Nerve conduction studies can be performed to detect the velocity at which signals travel along the nerve. Due to the destruction of myelin-associated with Leukodystrophies, nerve conduction may be at a reduced velocity or display abnormal patterns.

Krabbe disease is caused by a deficiency of the GALC enzyme. A blood or skin sample can be tested to measure GALC enzyme activity. Little or no activity can result in presence of the disease.

Genetic testing can determine particular mutations in our DNA that prevent the body from developing and maintaining healthy myelin.

The above tests will not indicate how quickly the disease will progress. Many mutations of the GALG gene exist, and the specific combination of mutations can cause symptoms and the rate of progression to vary significantly for each case.

Having Krabbe disease screening included as part of the Newborn Screening process allows Krabbe to be diagnosed before symptoms develop. At this point, there are possibilities of life-saving procedures.


For infants who have already developed symptoms of Krabbe Disease, as of yet there is no cure and the treatments are purely symptomatic and aimed at keeping the child as comfortable as possible.

  • For symptomatic treatment, the infant will be given anticonvulsants for seizure control. Medications will be given for control of muscle spasms. For slowing down the process of decreasing muscle tone, physical therapy will also be given to the child. It will be made sure that the child is given an ample amount of nutritional support as and when the child loses the ability to swallow. In these cases, foods and nutritional supplements can be given through gastric tubes.
  • On the other hand, older children who develop Krabbe Disease may be given physical and occupational therapy to help with decreasing muscle tone and make the child as independent as possible.
  • Stem Cell Transplantation. This is one of the newest forms of treatment for Krabbe Disease and has shown some promise especially in infants if done before the onset of symptoms. The stem cells contain microglia that are special cells which tend to reside in the nervous system.
  • Once stem cell transplantation from a healthy donor is done, then these microglia start accumulating in the nervous system and produce healthy GALC enzyme which helps in the formation of myelin sheaths. This may greatly slow down the progression of Krabbe Disease. Children receiving stem cell transplantation have significantly slowed the progression of Krabbe Disease but still experience plenty of difficulties, especially with walking and speech.
  • Anticonvulsants: Medications, called anticonvulsants, may be prescribed to treat seizures. These drugs are typically taken once daily to help prevent seizures from occurring. Phenobarbital (Luminal® Sodium) is one of the oldest and safest anticonvulsants for children. Side effects of phenobarbital may include drowsiness, cognitive impairment, and irritability. Valproic acid (Depakene® or Depakote®) has also been shown to be a safe and effective treatment for seizures in children. Side effects of valproic acid may include hepatotoxicity (liver damage), nausea, weight gain, hair loss, and tremors.

Prevention of krabbe disease

There is currently no known method of prevention against Krabbe disease.

  • If a person has a family history of Krabbe disease, genetic testing may be performed to determine if he/she carries the mutated gene. Although carriers do not have the disease, they can pass a copy of their mutated genes to their children.
  • Prenatal DNA testing may be performed if there is a family history of Krabbe disease. However, there are health risks associated with prenatal testing, including miscarriage. Therefore, patients should discuss the potential health risks and benefits with their healthcare provider before making any health-related decisions.
  • Before and after genetic testing, it is recommended that people meet with genetic counselors. These professionals can help patients understand the risks of having a child with Krabbe disease. A genetic counselor can also explain the different types of genetic tests, including their potential risks and benefits. These counselors can help patients understand the results and limitations of these tests.

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  1. so can that patient get cured completely

    • There is no cure for Krabbe disease. Recent studies have pointed to hematopoietic stem cell transplantation ( HSCT), stem cells that develop into blood cells, as a potential treatment for the condition. HSCT works best when it is given to patients who have not yet shown symptoms or are mildly symptomatic.

  2. thank you. children of 17 and 15 with such problem before knowing , is there any thing again to do to help them already with muscular seizure

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