Krabbe disease

Información en español Title

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:

Eye diseases; Newborn Screening

This disease is grouped under:

Leukodystrophy; Sphingolipidosis

Summary Summary

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

Symptoms Symptoms

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	Learn More: 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 seizures		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
Seizures	Seizure	0001250
Sensorimotor neuropathy	Nerve damage causing decreased feeling and movement	0007141
Vomiting	Throwing up	0002013

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2020

Do you have updated information on this disease? We want to hear from you.

Cause Cause

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

Inheritance Inheritance

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

Diagnosis Diagnosis

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.

Treatment Treatment

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

Prognosis Prognosis

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

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Related Diseases Related Diseases

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 Research

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.

Organizations Organizations

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

Alex The Leukodystrophy Charity (Alex TLC)
45 Peckham High Street
London, SE15 5EB United Kingdom
Telephone: 020 7701 4388
E-mail: info@alextlc.org
Website: https://www.alextlc.org
Hunter's Hope Foundation
6368 West Quaker Street
PO Box 643
Orchard Park, NY 14127
Toll-free: 877-984-4673
Telephone: 716-667-1200
Fax: 716-667-1212
E-mail: info@huntershope.org
Website: http://www.huntershope.org
Metabolic Support UK
5 Hilliards Court
Sandpiper Way
Chester Business Park
Chester, CH4 9QP United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: https://www.metabolicsupportuk.org/contact-us
Website: https://www.metabolicsupportuk.org
United Leukodystrophy Foundation (ULF)
224 North Second Street
Suite 2
DeKalb, IL 60115
Toll-free: 800-728-5483
Telephone: 815-748-3211
Fax: 815-748-0844
E-mail: office@ulf.org
Website: http://www.ulf.org/

Organizations Providing General Support

Do you know of an organization? We want to hear from you.

Living With Living With

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

The Social Security Administration has included this condition in their Compassionate Allowances Initiative. This initiative speeds up the processing of disability claims for applicants with certain medical conditions that cause severe disability. More information about Compassionate Allowances and applying for Social Security disability is available online.

Learn More Learn More

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.

GARD Answers GARD Answers

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.

Have a question? Contact a GARD Information Specialist.

References References

Wenger DA. Krabbe Disease. GeneReviews. March 31, 2011; http://www.ncbi.nlm.nih.gov/books/NBK1238/#krabbe.Clinical_Description.
David H Tegay, DO. Krabbe Disease. Medscape Reference. December 2014; http://emedicine.medscape.com/article/951722-overview.
Robert P Cruse, DO. Krabbe disease. UpToDate. February 2014; Accessed 7/2/2015.
Krabbe disease. Genetics Home Reference. August 2012; http://ghr.nlm.nih.gov/condition/krabbe-disease.
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.