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 infectionstage 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 skillsstage 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 patternsKrabbe 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 diagnosisWhere requested, enzymatic and genetic tests can be used to carry out prenatal diagnosis in specialised laboratories. Is there support? Krabbe UK Email: info@krabbeuk.orgWebsite: krabbeuk.org Krabbe UK is a Registered Charity in England and Wales No.1174472 and in Scotland No. SC047927. They provide information and support to families whose children are affected by Krabbe Leukodystrophy, champion research and raise awareness. Group details added July 2019. Information about all metabolic disorders is also available from Metabolic UK (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).
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 infectionstage 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 skillsstage 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 patternsKrabbe 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 diagnosisWhere requested, enzymatic and genetic tests can be used to carry out prenatal diagnosis in specialised laboratories.
Is there support? Krabbe UK Email: info@krabbeuk.orgWebsite: krabbeuk.org Krabbe UK is a Registered Charity in England and Wales No.1174472 and in Scotland No. SC047927. They provide information and support to families whose children are affected by Krabbe Leukodystrophy, champion research and raise awareness. Group details added July 2019. Information about all metabolic disorders is also available from Metabolic UK (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).