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Krabbe disease
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Krabbe Disease

Krabbe disease is a rare, severe leukodystrophy caused by mutations in the GALC gene, leading to demyelination and early childhood death.

Overview

Krabbe disease (also called globoid cell leukodystrophy) is a severe neurological condition. It is part of a group of disorders known as leukodystrophies, which result from the loss of myelin (demyelination) in the nervous system. Myelin is the protective covering around nerve cells that ensures the rapid transmission of nerve signals. Krabbe disease is also characterized by abnormal cells in the brain called globoid cells, which are large cells that usually have more than one .

Symptoms

The most common form of Krabbe disease, called the infantile form, usually begins before the age of 1. Initial signs and symptoms typically include irritability, muscle weakness, feeding difficulties, episodes of fever without any sign of infection, stiff posture, and delayed mental and physical development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures. Because of the severity of the condition, individuals with the infantile form of Krabbe disease rarely survive beyond the age of 2.

Less commonly, Krabbe disease begins in childhood, adolescence, or adulthood (late‑onset forms). Vision problems and walking difficulties are the most common initial symptoms in these forms of the disorder, however, signs and symptoms vary considerably among affected individuals. Individuals with late‑onset Krabbe disease may survive many years after the condition begins.

Causes & Risk Factors

Mutations in the GALC gene cause Krabbe disease. This gene provides instructions for making an enzyme called galactosylceramidase, which breaks down certain fats called galactolipids. One galactolipid broken down by galactosylceramidase, called galactosylceramide, is an important component of myelin. Breakdown of galactosylceramide is part of the normal turnover of myelin that occurs throughout life. Another galactolipid, called psychosine, which is formed during the production of myelin, is toxic if not broken down by galactosylceramidase.

GALC gene mutations severely reduce the activity of the galactosylceramidase enzyme. As a result, galactosylceramide and psychosine cannot be broken down. Excess galactosylceramide accumulates in certain cells, forming globoid cells. The accumulation of these galactolipids causes damage to myelin‑forming cells, which impairs the formation of myelin and leads to demyelination in the nervous system. Without myelin, nerves in the brain and other parts of the body cannot transmit signals properly, leading to the signs and symptoms of Krabbe disease.

Learn more about the gene associated with Krabbe disease

  • GALC

Inheritance

This condition is inherited in an autosomal recessive manner, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Frequency

In the United States, Krabbe disease affects about 1 in 100,000 individuals. A higher incidence (6 cases per 1,000 people) has been reported in a few isolated communities in Israel.

Other Names for This Condition

  • Diffuse globoid body sclerosis
  • Galactosylceramidase deficiency disease
  • Galactosylceramide lipidosis
  • Galactosylcerebrosidase deficiency
  • Galactosylsphingosine lipidosis
  • GALC deficiency
  • GCL
  • GLD
  • Psychosine lipidosis

Additional Information & Resources

Genetic Testing Information

  • Genetic Testing Registry: Galactosylceramide beta-galactosidase deficiency

Genetic and Rare Diseases Information Center

  • Krabbe disease

Patient Support and Advocacy Resources

  • National Organization for Rare Disorders (NORD)

Clinical Trials

  • ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

  • KRABBE DISEASE; KRB

Scientific Articles on PubMed

  • PubMed

References

  • Graziano AC, Cardile V. History, genetic, and recent advances on Krabbe disease. Gene. 2015 Jan 15;555(1):2-13. doi: 10.1016/j.gene.2014.09.046. Epub 2014 Sep 26. Citation on PubMed
  • National Institute of Neurological Disorders and Stroke: Krabbe Disease
  • Sakai N. Pathogenesis of leukodystrophy for Krabbe disease: molecular mechanism and clinical treatment. Brain Dev. 2009 Aug;31(7):485-7. doi: 10.1016/j.braindev.2009.03.001. Epub 2009 Mar 29. Citation on PubMed
  • Shin D, Feltri ML, Wrabetz L. Altered Trafficking and Processing of GALC Mutants Correlates with Globoid Cell Leukodystrophy Severity. J Neurosci. 2016 Feb 10;36(6):1858-70. doi: 10.1523/JNEUROSCI.3095-15.2016 Citation on PubMed or Free article on PubMed Central
  • Spratley SJ, Hill CH, Viuff AH, Edgar JR, Skjodt K, Deane JE. Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants. Traffic. 2016 Aug;17(8):908-22. doi: 10.1111/tra.12404. Epub 2016 May 30. Citation on PubMed or Free article on PubMed Central
  • Wenger DA, Rafi MA, Luzi P. Krabbe disease: One Hundred years from the bedside to the bench to the bedside. J Neurosci Res. 2016 Nov;94(11):982-9. doi: 10.1002/jnr.23743. Citation on PubMed

Medical Encyclopedia

  • Genetics
  • Krabbe disease

Understanding Genetics

  • What is the prognosis of a genetic condition?
  • How can gene variants affect health and development?
  • What does it mean if a disorder seems to run in my family?
  • What are the different ways a genetic condition can be inherited?
  • How

Frequently Asked Questions

While many infants experience some developmental variability, Krabbe disease often presents with a distinct cluster of symptoms before age one, including extreme irritability that is difficult to soothe, unexplained fevers without signs of infection, and a stiff, rigid posture. A key differentiator is the combination of these neurological signs with feeding difficulties and a noticeable lack of response to visual or auditory stimuli, which prompts clinicians to investigate for leukodystrophies rather than common viral illnesses or standard developmental issues.
The infantile form of Krabbe disease is currently incurable, and most individuals do not survive beyond the age of two without intervention. Hematopoietic stem cell transplantation (HSCT) can slow disease progression if performed very early, ideally before significant neurological damage occurs, but it does not reverse existing symptoms. Supportive care focuses on managing seizures, ensuring adequate nutrition, and maintaining comfort, with survival rates improving slightly with early aggressive management but remaining limited.
Diagnosis typically begins with newborn screening that measures the activity of the enzyme galactosylceramidase (GALC) in dried blood spots. A low enzyme level indicates a high risk for Krabbe disease and triggers confirmatory genetic testing to identify mutations in the GALC gene. It is important to note that enzyme levels can vary, so a borderline result may require repeat testing or direct genetic analysis to confirm the diagnosis before initiating treatment.
Krabbe disease is an autosomal recessive disorder, meaning a child must inherit two mutated copies of the GALC gene, one from each parent, to develop the condition. If a couple has one child with Krabbe disease, both parents are carriers, and there is a 25 percent chance with each subsequent pregnancy that the child will also have the disease. Genetic counseling is recommended for families to discuss carrier testing for relatives and reproductive options.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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