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

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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of the thumb	Very frequent (present in 80%-99% of cases)
Aplasia/Hypoplasia of the abdominal wall musculature	Very frequent (present in 80%-99% of cases)
Ataxia	Very frequent (present in 80%-99% of cases)
Cloverleaf skull	Very frequent (present in 80%-99% of cases)
EMG abnormality	Very frequent (present in 80%-99% of cases)
Feeding difficulties	Very frequent (present in 80%-99% of cases)
Sensorineural hearing impairment	Very frequent (present in 80%-99% of cases)
Sensory neuropathy	Very frequent (present in 80%-99% of cases)
Spasticity	Very frequent (present in 80%-99% of cases)
Visual impairment	Very frequent (present in 80%-99% of cases)
Fever	Frequent (present in 30%-79% of cases)
Gait disturbance	Frequent (present in 30%-79% of cases)
Generalized myoclonic seizures	Frequent (present in 30%-79% of cases)
Hemiplegia/hemiparesis	Frequent (present in 30%-79% of cases)
Irritability	Frequent (present in 30%-79% of cases)
Recurrent respiratory infections	Frequent (present in 30%-79% of cases)
Weight loss	Occasional (present in 5%-29% of cases)
Abnormal flash visual evoked potentials	-
Autoimmune thrombocytopenia	-
Autosomal recessive inheritance	-
Blindness	-
CNS demyelination	-
Decreased nerve conduction velocity	-
Developmental regression	-
Diffuse cerebral atrophy	-
EEG abnormality	-
Episodic fever	-
Failure to thrive	-
Hearing impairment	-
Hydrocephalus	-
Hyperactive deep tendon reflexes	-
Hypertonia	-
Increased CSF protein	-
Motor deterioration	-
Muscular hypotonia	-
Neurodegeneration	-
Nystagmus	-
Optic atrophy	-
Peripheral demyelination	-
Progressive spasticity	-
Seizures	-
Sensorimotor neuropathy	-
Vomiting	-

Last updated: 8/1/2017

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

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.^[5]^[1]^[3]

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.^[5]^[1]

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

Management Guidelines

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.

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.^[5]^[2]

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.^[5]^[2]

Last updated: 7/6/2015

Do you have updated information on this condition? Let us know.

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 studying or have studied 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

Children Living with Inherited Metabolic Diseases (CLIMB)
Climb Building
176 Nantwich Road
Crewe CW2 6BG
United Kingdom
Toll-free: 0800 652 3181
Telephone: 0845 241 2173
E-mail: contact@climb.org.uk
Website: http://www.climb.org.uk
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
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? Send us your suggestions.

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.

Genetics 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 GeneTests, 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.

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

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.

News & Events News & Events

News

IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

Gordon Research Conference and Gordon Research Seminar on Lysosomes and Endocytosis Sunday, June 15, 2014 - Friday, June 20, 2014
Location: Proctor Academy, Andover, NH
Description: The main goal of the Lysosomes and Endocytosis GRC is to foster the dissemination of current research results and the establishment of new research areas and new collaborations in the area of the cell biology of endocytosis, lysosomes, endosomes and related organelles. We hope that many of these new directions and collaborations will be directed toward the etiology, diagnosis and treatment of rare genetic diseases such as lysosomal storage disorders, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Niemann Pick disease and tuberous sclerosis, among others.

Contact: Alexandra Ainsztein, Ph.D.(301) 594-0828, Alexandra.Ainsztein@nih.gov

Co-funding Institute(s): National Institute of General Medical Sciences, Office of Rare Diseases Research
WORLD Symposium 2010 (Lysosomal Disease Network's 6th Annual Research Meeting) Wednesday, February 10, 2010 - Friday, February 12, 2010
Location: Miami Hilton Downtown, Miami, Florida
Description: The specific aims of this meeting were to (1) emphasize the strategies for, and identify the obstacles to, moving from translational research to clinical trials; (2) coalesce members of the LD network into functional research collaborations and present to the LDN community progress on the specific projects that are part of the funded U54 RDCRN grant; (3) foster interdisciplinary collaboration with the overall goal of improving knowledge of basic discoveries and clinical manifestations of these diseases; (4) provide an educational forum for young investigators, clinicians, and researchers in the field; (5) identify and discuss the latest findings in the natural history of lysosomal diseases, diagnostic testing and screening, and treatment, with specific focus on (a) inflammatory components of lysosomal diseases and autophagy, especially in the central nervous system, (b) new treatments of the central nervous systems, and (c) ethics and efficacy in treating the presymptomatic or asymptomatic patient; and (6) identify areas requiring additional basic and clinical research and public policy and regulatory attention, such as ethics and economics, and factors that impact implementation of therapy, including newborn screening.

Contact: Dr. Danilo A. Tagle(301) 496-5745tagled@mninds.nih.gov

Co-funding Institute(s): National Institute of Neurological Disorders and Stroke, Office of Rare Diseases Research
- Agenda ( - 2715KB)

Related Diseases Related Diseases

The following diseases are related to Krabbe disease. If you have a question about any of these diseases, you can contact GARD.

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. Submit a new question

Is it possible to be a carrier of the disease and have some symptoms of it as well? See answer
Does Krabbe disease take place more often in a certain gender? Does it take place more often in a certain ethnic group? See answer
My little baby has Krabbe disease. Here in Italy, doctors give us no chance. Can you help us? See answer
If a couple has a child with Krabbe leukodystrophy, what is the likelihood of having another child with the condition? See answer

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.