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 90% within the first 2 years.

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.

The back of an infant's head, possibly with Krabbe disease.Share on Pinterest
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Krabbe disease is a rare, inherited condition that affects the central nervous system (CNS) and peripheral nervous systems (PNS). Researchers have discovered that affected individuals have an inborn error of metabolism. It is rapidly progressive and fatal.

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

About 85–90% of people with the condition have the infantile form of Krabbe disease, which carries a high mortality rate within the first 2 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

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 more rapidly it progresses and the more likely it is to be fatal. Late onset types are milder and have a longer life expectancy.

Symptoms in children

A child with the early infantile type of Krabbe disease develops as expected until 4–6 months before the symptoms appear. The first symptoms include:

  • floppy to rigid muscle tone
  • hearing loss that leads to deafness
  • irritability
  • feeding difficulties
  • failure to thrive
  • hypersensitivity to loud sounds
  • severe seizures
  • visual problems leading to blindness
  • vomiting
  • unexplained fever

Symptoms in adults

Symptoms in late onset disease are generally similar to those in infants but progress more slowly.

The most common symptoms in these forms are vision problems, walking difficulties, and muscle rigidity. Other symptoms include:

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 prevents the body from making the enzyme GALC. This prevents the body from breaking down galactolipids such as psychosine and galactosylceramide.

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 6 per 1,000 live births due to the union among blood-related individuals.

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. include screening for Krabbe disease in the standard newborn screening protocol. This involves measuring the GALC enzyme from a blood or skin sample.

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:

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 are limited to infants with minimal to no symptoms.

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.

Other treatments

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.

Other small animal studies using combined therapeutic approaches also show success. Many clinical trials on Krabbe disease are ongoing around the world.

Supportive care

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 following complications:

Individuals with infantile disease have an average lifespan of 13 months and a mortality rate as high as 90% within 2 years.

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 effectiveness. Hence, early detection of the disease is critical.

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.