Globoid cell leukodystrophy
Krabbe disease is a rare, often fatal degenerative disorder that affects the myelin sheath of the nervous system. It is a form of sphingolipidosis, as it involves dysfunctional metabolism of sphingolipids. This condition is inherited in an autosomal recessive pattern. The disease is named after the Danish neurologist Knud Haraldsen Krabbe (1885-1965).
Illinois, Kentucky and Pennsylvania have laws to test for Krabbe and other diseases at birth. There is a movement in Maine and other states to adopt such regulations.
Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, fevers, limb stiffness, seizures, feeding difficulties, vomiting, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of cerebral palsy. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement, blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. Juvenile- and adult-onset cases of Krabbe disease also occur, which have similar symptoms but slower progression.
Krabbe disease is caused by mutations in the GALC gene located on chromosome (14q31), which causes a deficiency of an enzyme called galactosylceramidase. In rare cases it may be caused by a lack of active saposin A.
The build-up of unmetabolized lipids affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerves) and causes severe degeneration of motor skills. As part of a group of disorders known as leukodystrophies, Krabbe disease results from the imperfect growth and development of myelin.
GALC deficiency also results in a build-up of a glycosphingolipid called psychosine. Psychosine has been suggested to cause axonal degeneration in both the central and peripheral nervous systems by disrupting lipid rafts and may play a role in Krabbe disease.
A diagnosis of Krabbe disease is based on a series of tests, which may include the following.
A blood sample and small skin sample (biopsy) will be sent to a laboratory to assess the level of GALC enzyme activity. Very low or no GALC activity level may indicate Krabbe disease.
Although the results help a doctor make a diagnosis, they don't provide evidence of how quickly the disease may progress. For example, very low GALC activity doesn't always mean that the condition will advance rapidly.
Your doctor may order one or more imaging tests that can detect the loss of myelin (demyelination) in affected regions of the brain. These may include:
- Magnetic resonance imaging (MRI), a technology that uses radio waves and a magnetic field to produce detailed 3-D images
- Computerized tomography (CT), a specialized X-ray technology that produces 2-D images
Nerve conduction study
A nerve conduction study assesses the rate at which nerves conduct a signal — essentially how quickly can they send a message. A special device measures the time it takes an electrical impulse to travel from one point on the body to another. When myelin is impaired, nerve conduction is slower.
A genetic test may be done with a blood sample to confirm a diagnosis. There are variant forms of the mutated gene that results in Krabbe disease. The particular type of mutation may provide some clues regarding the expected course of the disease.
Genetic testing to understand the risk of having a child with Krabbe disease may be considered in certain situations:
- If one or both parents are likely carriers of a GALC gene mutation because of a known family history of Krabbe disease, a couple may want to have tests to understand the risks in their own family.
- If one child is diagnosed with Krabbe disease, a family may consider genetic tests to identify other children who could develop the disease later in life.
- If the parents are known carriers, they may request a prenatal genetic test to determine if their child is likely to develop the disease.
- Known carriers, who are using in vitro fertilization, may request a genetic test with fertilized eggs before implantation.
Genetic testing should be carefully considered. Ask your doctor about genetic counseling services that can help you understand the benefits, limits and implications of genetic testing.
In some states, a screening test for Krabbe disease is part of a standard set of assessments for newborns. The initial screening test measures GALC enzyme activity. If the enzyme activity is found to be low, follow-up GALC tests and genetic tests are conducted.
The use of newborn screening tests is relatively new. Researchers are still working to understand how best to use these tests, how well the tests lead to an accurate diagnosis and how well they predict the course of the disease.
In infants, the disease is generally fatal before age two. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.
Although no cure for Krabbe disease is known, bone marrow transplantation has been shown to benefit cases early in the course of the disease. Generally, treatment for the disorder is symptomatic and supportive. Physical therapy may help maintain or increase muscle tone and circulation. Cord blood transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.