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 affects the development and function of the nervous system. There are several types of Krabbe disease that differ based on the age that symptoms begin. The early-onset type of Krabbe disease is the most common and the most severe. Babies who have early-onset (infantile) Krabbe disease typically develop features in the first six months of life. Symptoms of infantile Krabbe disease may include irritability, failure to thrive, slowed development, and unexplained fevers. These are followed by progressive muscle weakness, hearing and vision loss, and decreased movement. Symptoms of the later-onset types of Krabbe disease start in childhood, early adolescence, or adulthood. These may include muscle weakness and stiffness, loss of milestones, blindness, behavior problems, dementia, and seizures. Krabbe disease is considered a fatal disease, and the average survival in the infantile type is 2 years. Krabbe disease is caused by genetic variants in the GALC gene and is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, clinical exam, imaging studies, and may be confirmed by the results of genetic testing. Krabbe disease can also be diagnosed based on the results of newborn screening. Treatment is focused on managing the symptoms. If the diagnosis is made before symptoms begin, hematopoietic stem cell transplant is an option for treatment.^[1]^[2]^[3]^[4]

Last updated: 12/11/2020

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with Krabbe disease. These features may be different from person to person. Some people may have more symptoms than others, and they can range from mild to severe. This list does not include every symptom that has been described in the condition.

Approximately 85-90% of people affected by Krabbe disease have the infantile type. Symptoms of this type may include:^[1]^[2]^[3]

Irritability
Increased muscle tone (hypertonia)
Developmental delay and/or regression
Unexplained fevers
Vomiting and other feeding difficulties
Vision loss
Slow growth (failure to thrive)
Damage to the nerves outside the brain and spinal cord (peripheral neuropathy)
Seizures
Hearing loss

The symptoms of Krabbe disease can develop at different ages. Babies affected by early-onset (infantile) type usually develop symptoms in the first six months. People with the late-onset types may not develop symptoms until later in childhood, adolescence or adulthood. 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. Life expectancy is reduced in all types of Krabbe disease. Without treatment, people with the early-onset type usually die by age 2.

Last updated: 12/14/2020

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
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

Showing of 27 |

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

Last updated: 2/1/2021

Cause Cause

Krabbe disease occurs when the GALC gene is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[1]

Last updated: 12/14/2020

Inheritance Inheritance

Krabbe disease is inherited in an autosomal recessive pattern.^[1] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Recessive means that both copies of the responsible gene must have a pathogenic variant to have the condition.

People with autosomal recessive conditions inherit one variant from each of their parents. The parents, who each have one gene variant, are known as carriers. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, there is a 25% (1 in 4) chance to have a child with the condition.

Last updated: 12/14/2020

Diagnosis Diagnosis

Krabbe disease is diagnosed based on the symptoms, clinical exam, and additional testing to check for the level of an enzyme that is low in people with Krabbe disease. This testing generally includes a blood test and/or skin biopsy. Diagnosis may be confirmed by the results of genetic testing. In some cases, Krabbe disease is diagnosed based on the results of an abnormal newborn screen.^[1]^[4]

Last updated: 12/14/2020

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.

Treatment Treatment

Treatment of Krabbe disease is focused on managing the symptoms and providing support. Hematopoietic stem cell transplantation (i.e. umbilical cord blood stem cells) is an option for treatment in babies with Krabbe disease who have not yet developed symptoms. The outcome of a stem cell transplant for people with Krabbe disease differs based on the age at diagnosis and the severity and presence of symptoms before the transplant.^[1]^[2]^[4]

Specialists involved in the care of someone with Krabbe disease may include:

Neurologist
Ophthalmologist
Otolaryngologist
Medical geneticist
Gastroenterologist
Physical therapist
Occupational therapist

Last updated: 12/14/2020

Statistics Statistics

It has been estimated that between 1/100,000 to 1/250,000 people has Krabbe disease.^[1]^[4] The exact number of people with Krabbe disease is unknown.

Last updated: 12/14/2020

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

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 MedlinePlus Genetics.

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

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

Organizations Providing General Support

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
United Leukodystrophy Foundation (ULF)
224 North Second Street
Suite 2
DeKalb, IL 60115
Toll-free: 1-800-728-5483
Telephone: +1-815-748-3211
Fax: +1-815-748-0844
E-mail: office@ulf.org
Website: https://ulf.org/

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

MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
Genetics Home Reference (GHR) contains information on Krabbe disease. This website is maintained by the National Library of Medicine.
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

Orsini JJ, Escolar ML, Wasserstein MP, Caggana M. Krabbe Disease. GeneReviews. Updated Oct 11, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1238/.
Jain M, De Jesus O. Krabbe Disease. StatPearls. Updated Nov 14, 2020; https://pubmed.ncbi.nlm.nih.gov/32965986/.
Komatsuzaki S,Zielonka M, Mountford WK, Kölker S, Hoffmann GF, Garbade SF, Ries M.. Clinical characteristics of 248 patients with Krabbe disease: quantitative natural history modeling based on published cases.. Genet Med. Oct 2019; 21(10):2208-2215. https://pubmed.ncbi.nlm.nih.gov/30899093/.
Kwon JM, Matern D, Kurtzberg J, Wrabetz L, Gelb MH, Wenger DA, Ficicioglu C, Waldman AT, Burton BK, Hopkins PV, Orsini JJ. Consensus guidelines for newborn screening, diagnosis and treatment of infantile Krabbe disease. Orphanet J Rare Dis.. Feb 1 2018; 13(1):30. https://pubmed.ncbi.nlm.nih.gov/29391017/.