Krabbe disease is a rare genetic disorder in which a person lacks an enzyme that breaks down specific lipids. The lipid buildup progressively destroys the nervous system, causing neurological symptoms and eventually leading to death.
Most individuals with Krabbe disease develop the condition in infancy. Among this group, there is a mortality rate of up to
There is no cure for Krabbe disease, but treatment can help to manage symptoms and improve quality of life.
This article explores what Krabbe disease is, its symptoms, causes, diagnosis, and more.
Krabbe disease is a
Also known as globoid cell leukodystrophy, Krabbe disease is classified as a leukodystrophy and a lysosomal storage disorder (LSD). LSDs occur when a cell’s recycling component, called the lysosome, does not work properly.
Leukodystrophies are a group of inherited brain disorders that cause the progressive breakdown of the myelin sheath of the nerves in the brain.
In Krabbe disease, the lack of an enzyme in the lysosome causes a toxic buildup that leads to the destruction of myelin. The myelin sheath is a layer of fat and protein that insulates and covers the nerves in the brain. It protects the nerves and allows impulses to travel quickly.
Damage to the myelin sheath causes impulses to slow down and stop, causing the underlying nerve fibers to die.
Krabbe disease has four subcategories depending on when the symptoms first appear:
- early infantile type: 0–13 months
- late infantile type: 13–36 months
- juvenile type: 3–16 years
- adult type: Over 16 years
The condition gets its name from Knud Krabbe, the first doctor to describe the condition. It is also called globoid cell leukodystrophy because of the characteristic presence of globoid cells — abnormal cells that have more than one nucleus — in the brain.
Other names for Krabbe disease include:
- galactosylcerebrosidase (GALC) deficiency
- galactosylceramide lipidosis
- galactosylsphingosine lipidosis
- psychosine lipidosis
The presentation and severity of the disease vary based on the age when symptoms first appear.
Children with the disease generally develop symptoms during their first year of life. Less commonly, the condition may be late onset and begin in childhood, adolescence, or adulthood.
The earlier the age of onset, the
Symptoms in children
A child with the early infantile type of Krabbe disease develops as expected until
- floppy to rigid muscle tone
- hearing loss that leads to deafness
- feeding difficulties
- failure to thrive
- hypersensitivity to loud sounds
- severe seizures
- visual problems leading to blindness
- unexplained fever
Symptoms in adults
Symptoms in late onset disease are
The body produces toxic products called galactolipids during the production of myelin. The enzyme galactosylceramidase (GALC) quickly breaks this down. GALC is one of the many enzymes found in lysosomes, the part of the cell that breaks down toxins.
In Krabbe disease, a gene defect in chromosome 14
The galactolipid buildup in the CNS and PNS destroys myelin, or the brain’s white matter.
Krabbe is a type of autosomal recessive disease. This means the affected individual has one defective copy of the GALC gene from each parent.
Krabbe disease is a rare condition. It affects only about 1 in 100,000 people in the United States.
However, its rate in some Israeli communities is as high as
Krabbe disease is an autosomal recessive disorder. If both parents are carriers of the mutated gene, a person has:
- a 25% chance of developing the disease
- a 25% chance of not developing the disease and not carrying the mutated gene
- a 50% chance of carrying the mutated gene without developing the disease
Many states in the U.S.
However, this test is not diagnostic. Additional tests are needed to confirm the diagnosis.
A doctor may ask a person to undergo other tests, including:
- CT scan
- magnetic resonance imaging (MRI)
- magnetic resonance spectroscopy
- electroencephalography (EEG)
- eye and ear examination
- lumbar puncture to look for elevated CSF protein level
- genetic testing
- electromyography (EMG)
- nerve conduction velocity
- amniocentesis and chorionic villus sampling
Brain biopsy can also reveal Krabbe disease. Typical findings show:
- demyelination of brain white matter
- loss of oligodendroglial cells
- areas of brain shrinkage (atrophy)
- presence of globoid cells
There is currently no cure for Krabbe disease. Treatments
Hematopoietic stem cell transplant
Hematopoietic stem cell transplant (HSCT) aims to transplant healthy stem cells into a patient. The treatment helps populate the person’s brain with healthy microglia and good GALC enzyme activity.
HSCT helps slow down or plateau the progression of the disease and works best when given before the onset of symptoms.
Cord blood stem cell transfusion
This procedure involves collecting cord blood stem cells from an unrelated donor’s umbilical cord and transfusing them to the person with Krabbe disease.
A 2020 canine study found that intrathecal gene therapy successfully prevented neurological damage in dogs. Treated dogs live seven times longer than untreated ones. It is still unknown whether the results translate to humans.
Until better treatment options become available for people with Krabbe disease, supportive and palliative care are the only treatments healthcare professionals can give. These include:
The disease progressively damages the nerves in the central nervous system. This can cause the
- severe muscle tone problems
- intellectual disability
Individuals with infantile disease have an average lifespan of 13 months and a mortality rate as high as
Individuals predicted to have the infantile disease who receive treatment before their first month of life may live up to the second decade.
Those with late infantile type who showed symptoms between 13 and 36 months old have an average life expectancy of 6 years.
The disease progression and life expectancy of individuals who develop the condition during adolescence or adulthood vary. The disease is typically fatal 2–7 years after symptoms first appear. A person may survive into adulthood with nervous system disease.
Providing treatment for a child before symptoms occur can greatly enhance their
A blood test can identify whether a person carries the gene for the disease. Individuals with a family history of the disease who are considering having a baby may undergo genetic counseling.
Prenatal testing, such as amniocentesis or chorionic villus sampling, can identify whether the developing baby has the condition.
Krabbe disease is a rare and fatal disorder that affects the nervous system. It often affects infants but may rarely appear in childhood, adolescence, or adulthood.
There is currently no cure for the condition. However, hematopoietic stem cell treatment (HCST) and other treatments may delay its progression.