National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Krabbe disease

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Other Names:
Krabbe leukodystrophy; Globoid cell leukodystrophy; GCL; Krabbe leukodystrophy; Globoid cell leukodystrophy; GCL; Globoid cell leukoencephalopathy; Galactosylceramide beta-galactosidase deficiency; GALC deficiency; GLD; Galactocerebrosidase deficiency See More
Categories:
This disease is grouped under:
Krabbe disease is an inherited condition that affects the nervous system. The signs and symptoms of the condition and the disease severity differ by type. Babies affected by early-onset (infantile) Krabbe disease, the most common and severe form of the condition, typically develop features in the first six months of life. Symptoms of infantile Krabbe disease may include irritability; failure to thrive; slowed development; unexplained fevers; and progressive muscle weakness, hearing loss and vision loss. People affected by the late-onset forms may not develop symptoms until later in childhood, early adolescence or even into adulthood. Signs and symptoms of these forms are extremely variable but may include muscle weakness and rigidity; walking difficulties; vision loss; intellectual regression; and/or seizures. Krabbe disease is caused by changes (mutations) in the GALC gene and is inherited in an autosomal recessive manner. Treatment is generally based on the signs and symptoms present in each person; however, preliminary studies suggest that it may be beneficial to use hematopoietic stem cell transplantation (i.e. umbilical cord blood stem cells) as a treatment for patients in the early stages of infantile Krabbe disease and older people with mild symptoms.[1][2][3]
Last updated: 10/9/2015
The signs and symptoms of Krabbe disease can develop at different ages. Babies affected by early-onset (infantile) Krabbe disease typically develop features in the first six months of life, while people affected by the late-onset forms may not develop symptoms until later in childhood, early adolescence or even into adulthood.[1]

Approximately 85-90% of people affected by Krabbe disease have the infantile form which is characterized by the following features:[1][2][3]
  • Irritability
  • Hypertonia
  • Sensitivity to loud sounds
  • Developmental delay and/or regression
  • Unexplained fevers
  • Vomiting and other feeding difficulties
  • Vision loss
  • Failure to thrive
  • Peripheral neuropathy
  • Seizures
  • Hearing loss

Signs and symptoms of the later-onset forms are extremely variable but may include muscle weakness and rigidity; walking difficulties; vision loss; intellectual regression; and/or seizures.[1]

Last updated: 7/5/2015

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Abnormal thumb morphology
Abnormality of the thumb
Abnormality of the thumbs
Thumb deformity
[ more ] 		0001172
Aplasia/Hypoplasia of the abdominal wall musculature
Absent/small abdominal wall muscles
Absent/underdeveloped abdominal wall muscles
[ more ] 		0010318
Ataxia 0001251
Cloverleaf skull 0002676
EMG abnormality 0003457
Feeding difficulties
Feeding problems
Poor feeding
[ more ] 		0011968
Global developmental delay 0001263
Sensorineural hearing impairment 0000407
Sensory neuropathy
Damage to nerves that sense feeling
0000763
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
30%-79% of people have these symptoms
Fever 0001945
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Generalized myoclonic seizure 0002123
Hemiplegia/hemiparesis
Paralysis or weakness of one side of body
0004374
Irritability
Irritable
0000737
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
5%-29% of people have these symptoms
Weight loss 0001824
Percent of people who have these symptoms is not available through HPO
Abnormal flash visual evoked potentials 0007928
Autoimmune thrombocytopenia 0001973
Autosomal recessive inheritance 0000007
Blindness 0000618
CNS demyelination 0007305
Decerebrate rigidity 0025013
Decreased nerve conduction velocity 0000762
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood
[ more ] 		0002376
Diffuse cerebral atrophy 0002506
EEG abnormality 0002353
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hyperactive deep tendon reflexes 0006801
Hypertonia 0001276
Increased CSF protein 0002922
Motor deterioration
Progressive degeneration of movement
0002333
Muscular hypotonia
Low or weak muscle tone
0001252
Neurodegeneration
Ongoing loss of nerve cells
0002180
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy 0000648
Peripheral demyelination 0011096
Progressive spasticity 0002191
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever
[ more ] 		0001954
Seizure 0001250
Sensorimotor neuropathy
Nerve damage causing decreased feeling and movement
0007141
Vomiting
Throwing up
0002013
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Last updated: 7/1/2020
Krabbe disease is caused by changes (mutations) in the GALC gene. This gene provides instructions for making an enzyme called galactosylceramidase, which breaks down a certain type of fat that is primarily found in the brain and kidneys. Mutations in the GALC gene lead to reduced levels of the galactosylceramidase enzyme which can cause a build up of toxic fats in the cells of the brain and other tissues. This may result in the progressive loss of myelin, the protective covering around certain nerve cells that ensures the rapid transmission of nerve impulses. Without myelin, nerves in the brain and other parts of the body cannot function properly, leading to the signs and symptoms of Krabbe disease.[4]
Last updated: 7/5/2015
Krabbe disease is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.
Last updated: 7/5/2015
A diagnosis of Krabbe disease may be suspected based on the presence of characteristic signs and symptoms or in certain states of the United States, due to an abnormal newborn screen. Additional testing can then be ordered to confirm the diagnosis. This testing generally includes a blood test and/or skin biopsy to evaluate the levels of galactosylceramidase, the enzyme that is low in people with Krabbe disease. Genetic testing for changes (mutations) in the GALC gene can also confirm the diagnosis.[1][3]
Last updated: 7/5/2015

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
  • Orphanet lists international laboratories offering diagnostic testing for this condition.

Newborn Screening

  • An ACTion (ACT) sheet is available for this condition that describes the short-term actions a health professional should follow when an infant has a positive newborn screening result. ACT sheets were developed by experts in collaboration with the American College of Medical Genetics.
  • Baby's First Test is the nation's newborn screening education center for families and providers. This site provides information and resources about screening at the local, state, and national levels and serves as the Clearinghouse for newborn screening information.
  • National Newborn Screening and Global Resource Center (NNSGRC) provides information and resources in the area of newborn screening and genetics to benefit health professionals, the public health community, consumers and government officials.
Unfortunately, there is no cure for Krabbe disease. However, preliminary studies suggest hematopoietic stem cell transplantation (i.e. umbilical cord blood stem cells) may be an effective treatment in affected babies who have not yet developed symptoms and in older people with mild symptoms. For example, there is evidence that this treatment may delay disease progression and improve survival and quality of life. Although both short-term and long-term benefits have been reported, the data comes primarily from small clinical trials; thus, additional research is needed to more clearly define the outcomes of this treatment.[1][3][5]

When a diagnosis is made after a person has already developed symptoms, treatment is focused on the symptoms present and may include various medications, adaptive equipment and therapies - including physical, respiratory, occupational, and speech.[1][5]

The advocacy organization, Hunter's Hope, offers a family resource guide that includes information on the supportive treatment of Krabbe disease as well as tips for caring for an affected child. Please click on the link to access this resource.
Last updated: 7/6/2015
The long-term outlook (prognosis) for people with Krabbe disease varies by type. Infantile Krabbe disease is generally fatal before age two. However, prognosis may be better for children who receive umbilical cord blood stem cells prior to disease onset or early bone marrow transplantation.[2][5]

People with later-onset Krabbe disease generally have a milder course of the disease. However, the progression of disease and lifespan reduction can vary significantly.[2][5]
Last updated: 7/6/2015

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes metachromatic leukodystrophy, GM1 gangliosidosis, GM2 gangliosidosis, Canavan disease, encephalopathy due to prosaposin deficiency, X-linked adrenoleukodystrophy, Pelizaeus-Merzbacher disease and Alexander disease (see these terms).
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Krabbe disease. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Patient Registry

  • The Lysosomal Disease Network is a team of doctors, nurses, research coordinators, and research labs throughout the U.S., working together to improve the lives of people with this condition through research. The Lysosomal Disease Network has a registry for patients who wish to be contacted about clinical research opportunities.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Financial Resources

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Krabbe disease. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Krabbe disease. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Wenger DA. Krabbe Disease. GeneReviews. March 31, 2011; http://www.ncbi.nlm.nih.gov/books/NBK1238/#krabbe.Clinical_Description.
  2. David H Tegay, DO. Krabbe Disease. Medscape Reference. December 2014; http://emedicine.medscape.com/article/951722-overview.
  3. Robert P Cruse, DO. Krabbe disease. UpToDate. February 2014; Accessed 7/2/2015.
  4. Krabbe disease. Genetics Home Reference. August 2012; http://ghr.nlm.nih.gov/condition/krabbe-disease.
  5. NINDS Krabbe Disease Information Page. National Institute of Neurological Disorders and Stroke (NINDS). https://www.ninds.nih.gov/Disorders/All-Disorders/Krabbe-Disease-Information-Page.