Krabbe disease, or globoid cell leukodystrophy, is a rare genetic condition that is caused by deficiency of the enzyme galactosylceramidase (GALC). It is characterised by: myelin degeneration, an abnormal amount of toxic lipids including psychosine in the central and peripheral nervous systems, and globoid cells in the brain.  

Continue reading to learn more about the main causes of Krabbe disease, its signs, symptoms and treatment options, whether you, or any children under your supervision are at risk of developing the disease. Additionally, what to expect of Krabbe disease, and much, much more!  

Overview

Krabbe disease (pronounced ‘’crab-ay’’) or globoid cell leukodystrophy,¹ is a type of leukodystrophy and lysosomal storage disorder that affects the myelin (also referred to as ‘’white matter’’) of the central (brain and spinal cord) and peripheral (nerves) nervous systems. 

Krabbe disease is named after Knud Krabbe, a Danish neurologist who first described the rare disease in 1916.²  

Causes of Krabbe disease

Krabbe disease is mainly caused by mutations (changes in the sequence of DNA) or defects in the GALC gene.³ This gene is necessary for the production of an enzyme (protein) called galactosylceramidase (GALC) (or galactocerebrosidase). 

Localised within lysosomes (organelles that, much like ‘recycling bins’, clean up cellular waste) in the brain and spinal cord, galactosylceramidase breaks down certain fats including galactolipids mainly into galactosylceramide or psychosine. Galactosylceramide is an important component of myelin. Psychosine, on the other hand, prevents the production of myelin and is toxic if not broken down. 

Because there is a deficiency or lack of activity of the lysosomal galactosylceramidase enzyme,³ excess lipids (fats) including galactosylceramide accumulate in the body  mainly within brain cells. As a result, large abnormal cells with more than one nucleus termed globoid cells (hence globoid cell leukodystrophy) form in the brain. Globoid cells break down the myelin sheath (‘’demyelination’’) that protects nerve cells.  

Demyelination³ prevents transmission of nerve signals between the central and peripheral nervous systems, leading to the neurological signs and symptoms of Krabbe disease. 

In Krabbe disease, the GALC gene mutations are inherited in an autosomal recessive pattern,³ meaning that both copies of the gene from each parent carry a mutation. 

Signs and symptoms of Krabbe disease

The signs and symptoms of Krabbe disease vary depending on age of onset.⁴ 

Typically, early infantile Krabbe disease (between 1 and 7 months old) is more severe than late-onset Krabbe disease (18 months onwards) because it progresses more rapidly and is typically fatal by the time infants reach the age of two.

Signs and symptoms of early infantile Krabbe disease:⁴

• Restlessness
• Irritability 
• Vomiting
• Muscle weakness 
• Episodes of fever without infection
• Hearing and vision loss
• Seizures 
• Difficulty to eat, breathe and move  
• Peripheral neuropathy (severe nerve damage)

Signs and symptoms of late-onset Krabbe disease:^3,4

• Walking difficulties 
• Vision changes and vision loss

Management and treatment for Krabbe disease

Treatment for Krabbe disease

Unfortunately, there is no cure⁴ for Krabbe disease.

However, hematopoietic stem cell transplant (HSCT) is currently available and helps improve GALC activity, thus slowing down disease progression.  

Hematopoietic stem cells are cells that can divide and develop into all types of blood cells including red blood cells, white blood cells and platelets. 

HSCT⁴ works by replacing the unhealthy hematopoietic cells of affected infants and children with Krabbe disease with healthy or normal hematopoietic cells from healthy donors. 

Management for Krabbe disease

Krabbe disease can be managed through the use of the following methods with the help of supportive caregivers:⁴

• Muscle relaxants
• Anticonvulsant medications
• Physical therapy
• Occupational therapy
• Tube feedings

Diagnosis of Krabbe disease

In order to diagnose an individual with Krabbe disease, a general practitioner (GP) or healthcare provider will performa series of diagnostic tests⁵ in the following order: 

1. Medical history and physical exam
2. Laboratory tests: these involve taking blood, urine or tissue samples to assess GALC activity
3. Imaging studies: particularly via the use of magnetic resonance imaging (MRI). MRI helps identify brain lesions in children with Krabbe disease

An early diagnosis of Krabbe disease can also be provided upon confirmatory testing via newborn screening.⁵ Newborn screening involves taking a blood sample from newborns before leaving the hospital and testing for over 30 genetic diseases. 

If a child is diagnosed with Krabbe disease, the healthcare provider will likely recommend the following tests:⁴ 

• A hearing and vision test: to determine the severity and degree of hearing and vision loss
• Genetic testing: to confirm or rule out Krabbe disease
• Genetic counselling: with the help of a genetic counsellor, genetic counselling evaluates the likelihood that the parents will have more thanone child with the rare disease

FAQs

How can I prevent Krabbe disease?

Krabbe disease cannot be prevented⁴ as it is an inherited genetic condition. 

Who is at risk of Krabbe disease? 

Children whose parents carry one copy of the mutated GALC gene have a 1 in 4 (25%) chance or risk¹ of developing Krabbe disease. 

How common is Krabbe disease?

Krabbe disease is very rare,⁴ with a frequency of approximately 1 in 100,000 live births in Europe. 

What can I expect if I have Krabbe disease?

A progressive worsening of signs and symptoms⁴ is typical. The outcome of the disease (prognosis) is poor and death usually occurs due to respiratory failure. 

When should I see a doctor?

See a doctor if you have:⁴

• New and/or exacerbating symptoms

• The mutated GALC gene and want to consider genetic counselling with a genetic counsellor

Summary

Krabbe disease, or globoid cell leukodystrophy, is a rare, severe, neurodegenerative and autosomal recessive lysosomal storage disorder. It is caused by a deficiency of the enzyme galactosylceramidase due to mutations in the GALC gene, resulting in demyelination, and the accumulation of excess toxic lipids such as psychosine, mainly in brain cells. 

Signs and symptoms of Krabbe disease vary depending on the age of onset, with the early-onset infantile form being more severe than the late-onset form of Krabbe disease. Early infantile Krabbe disease patients do not often make it past the age of 2, mainly due to respiratory failure. 

To date, Krabbe disease cannot be cured or prevented. However, it can be managed and treated via supportive care and hematopoietic stem cell transplant, respectively.  

Krabbe disease is typically diagnosed based on signs and symptoms, imaging studies (e.g. MRI) and clinical procedures (e.g. hearing tests). Diagnosis of Krabbe disease can be aided or confirmed via newborn screening and genetic testing, respectively.  

A GP or healthcare provider might refer parents who are both carriers of the mutated GALC gene to a genetic counsellor for genetic counselling. 

See a doctor if: 

• Symptoms worsen 
• New symptoms arise