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Krabbe disease

Also known as: Galactosylceramidase Deficiency, Galactosylcerebrosidase Deficiency, Globoid Cell Leukodystrophy

Background

Krabbe disease is a rare genetic condition in which the white matter of the nervous system degenerates. It is one of a disease group, the leukodystrophies - a term originating from the Greek, 'leuko' (referring to the 'white' matter of the nervous system); and 'dystrophy', which refers to imperfect growth or development. The white matter of the nervous system is composed of myelin - a fatty cover which acts as an insulator around nerve fibres. Krabbe disease may be identified by the presence of globoid cells (large scavenging cells usually with more than one nucleus) in association with a breakdown of the protective myelin coating of nerves - ultimately with loss of brain cells.

Credits

Last updated April 2015 by Professor T Cox, Professor of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.

What are the symptoms?

The onset of Krabbe disease usually occurs between the ages of three to six months. Features include irritability, choking, loss of developmental and motor skills, myoclonic and general seizures (see entry Epilepsy), blindness, spasticity (stiffness of the limbs), paralysis and weight loss; unexplained fevers are noted in the last phases.

There are three stages of the condition:

  • stage I - general irritability, stiffness, arrest of motor and mental development and episodes of high temperature without the presence of an infection
  • stage II - infants may have severe arching of the back and have myoclonic-like jerks of the arms and legs, hypertonic fits, bouts of fever and loss of learned skills
  • stage III - infants are severely impaired with no voluntary movement.

The average age of death is between 13 months to 2 years, although infections and respiratory failure may bring about an earlier death.

Besides this most frequent infantile form, there are also juvenile and adult forms of Krabbe disease. These variants become apparent later, progress more slowly and those affected may live well into middle age - with perhaps only leg stiffness and sometimes painful nerve roots.

What are the causes?

The myelin sheath is a complex of many components. Krabbe disease is caused by reduced activity of an enzyme known as galactocerebrosidase (GALC), which is encoded as a gene on chromosome 14.

How is it diagnosed?

Although characteristic features of Krabbe disease may be identified in brain tissue, diagnosis of this condition is usually suspected from MRI appearances and confirmed by a special blood test that measures the activity of GALC. In some cases analysis of the GALC gene is carried out to confirm the diagnosis.

How is it treated?

Although there is no specific cure for Krabbe disease, the results of umbilical cord blood transplantation from unaffected donors has been reviewed. Neonatal transplant of umbilical cord blood significantly modifies a severe disease when given to newborn infants who are known to carry two copies of the causal gene. However, there are long-term risks from the procedure and the appearance of Krabbe disease is not prevented by this treatment. Bone marrow or now blood stem-cell transplantation (HSCT) may have a role in late-onset or adult forms of the condition where it may prevent further progression of the established disease.

Treatment of infants when manifestations are evident is limited to supportive care to control irritability and spasticity. Some symptoms, however, can be treated and physical therapy can help muscle tone and coordination.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Krabbe disease is inherited as an autosomal recessive trait and, because of this, the disorder may appear suddenly with no prior history in the family.

Prenatal diagnosis
Where requested, enzymatic and genetic tests can be used to carry out prenatal diagnosis in specialised laboratories.

 

Is there support?

Save Babies Through Screening Foundation UK

Tel: 01943 878 770
Email: info@savebabiesuk.org
www.savebabiesuk.org

The Foundation is a Registered Charity in England and Wales No. 1133080. It provides information and support to families whose children are affected by Krabbe disease and other Leukodystrophies. The Foundation works to promote the extension of the newborn screening programme in the UK for all treatable inherited metabolic disorders.

Group details last updated March 2016.

Information about all metabolic disorders is also available from Climb (see entry Inherited Metabolic diseases).

Support for the dementia aspects of Krabbe disease in adults can be obtained from the Alzheimer's Society (see entry Alexander disease).