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Disease Profile

Krabbe disease

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

E75.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Krabbe leukodystrophy; Globoid cell leukodystrophy; GCL;

Categories

Eye diseases; Newborn Screening

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]

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. 

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.

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

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]

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]

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 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

      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

        Organizations Providing General Support

          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.

              References

              1. Orsini JJ, Escolar ML, Wasserstein MP, Caggana M. Krabbe Disease. GeneReviews. Updated Oct 11, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1238/.
              2. Jain M, De Jesus O. Krabbe Disease. StatPearls. Updated Nov 14, 2020; https://pubmed.ncbi.nlm.nih.gov/32965986/.
              3. 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/.
              4. 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/.

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