Krabbe disease is a devastating genetic disorder that damages the brain and nerves. Individuals with Krabbe disease do not make enough of an enzyme called galactocerebrosidase (also called galactosylceramidase, or GALC) due to changes or mutations in the galactosylceramidase (GALC) gene. Without enough of this enzyme, complex fatty substances called psychosine and galactocerebroside build up in the nerve tissues of the body. In large amounts, these substances are poisonous to the cells of the body that make myelin, a covering or "sheath" that coats, protects, and insulates nerves. If you think of an electric cord, the myelin is similar to the plastic covering the protects the wires underneath. If there isn’t myelin, it is like not having that plastic covering and the wires, aka nerves, are exposed and more easily damaged. Collectively, myelin-covered nerve fibers are known as the white matter. Krabbe disease slowly damages the white matter of the brain and the rest of the central nervous system (the spinal cord). The white matter of the nerves outside the central nervous system (the peripheral nervous system) is also damaged by Krabbe disease. The term that is used to describe this loss of myelin and white matter is demyelination.
Krabbe Disease Spectrum
There is a spectrum of severity within Krabbe disease, with the infantile form on one end of the spectrum and the adult-onset forms at the other. The infantile form of Krabbe disease is the most severe. Babies diagnosed with this form usually have noticeable symptoms happening in the first six months of life. Babies with the infantile form gradually lose the ability to sit up, babble, smile, and see. If left untreated, these babies often pass away by 2-3 years of age. At other points along the spectrum of disease severity, Krabbe disease symptoms do not appear until later in childhood, adolescence, or even in adulthood. The age when symptoms first appear, the health problems that develop and the rate at which the disorder gets worse can vary in different people. Except for a few well understood infantile forms of Krabbe, it can be very difficult to tell what health problems a person will have simply from their genetic variants (mutations).
There is a spectrum of severity within Krabbe disease, with the infantile form on one end of the spectrum and the adult-onset forms at the other. The infantile form of Krabbe disease is the most severe. Babies diagnosed with this form usually have noticeable symptoms happening in the first six months of life. Babies with the infantile form gradually lose the ability to sit up, babble, smile, and see. If left untreated, these babies often pass away by 2-3 years of age. At other points along the spectrum of disease severity, Krabbe disease symptoms do not appear until later in childhood, adolescence, or even in adulthood. The age when symptoms first appear, the health problems that develop and the rate at which the disorder gets worse can vary in different people. Except for a few well understood infantile forms of Krabbe, it can be very difficult to tell what health problems a person will have simply from their genetic variants (mutations).
Inheritance
Krabbe disease runs through families in an autosomal recessive pattern. Autosomal recessive means that a person will have the condition if they have two disease-causing (pathogenic) variants in the same gene. It also usually means that each parent must be a carrier (have a single Krabbe disease genetic variant) and both pass on the gene changes to their child. If both parents are carriers, then there is a 25% chance that each child they have will have Krabbe disease. If only one parent passes on their Krabbe disease genetic variant (50% change), then the child with be unaffected carrier (just like their parent)
Testing For Krabbe Disease
Cove’s law has granted Georgia parents the option to screen their newborns for Krabbe disease. Interested parents need to coordinate testing for Krabbe disease with their doctor as it is not done automatically with the rest of the Georgia newborn screening panel. Emory is committed to providing quality care for families that choose to pursue this screening and now offers kits to facilitate this process.
Screening Tests for Krabbe Disease
Screening for Krabbe disease can be done at birth on cord blood or a dried blood spot. For both options you should notify your Ob-Gyn that you want screening so that they can provide you with all necessary materials before your delivery date. Cord Blood Testing is noninvasive. It requires two test tubes to be filled with umbilical cord blood immediately after birth. This option is preferred when the sample can be tested within 72 hours of blood sample collection. This means a sample is best drawn Monday through Thursday only and not the day before a holiday as labs are closed on weekends and holidays. A dried blood spot requires that dried blood spots be collected from either cord blood or baby’s heel using a special filter paper. Dried Blood Spots are routinely taken from newborns for screening and can be the best option if a baby is born on a weekend.
If you did not plan to have testing prior to a baby’s birth, testing is still available, but typically by dried blood spot or by drawing a tube of blood. Given the early impact of infantile Krabbe disease, the sooner a baby tested, the more treatment options will be available for the baby.
Parents must ask their doctor to decide which lab will process their baby’s sample based on their insurance coverage. Emory genetic counselors are also available to help guide patients through this process if necessary.
Cost
At this time, Krabbe testing is NOT provided as part of the standard Georgia newborn screening panel. Parents should check with their insurance provider to review coverage of the test, Galactocerebrosidase on leukocytes (CPT code 82658). Testing is usually covered by insurance. If insurance does not cover the testing, the list price of screening is between $175-300 depending on the laboratory.
Positive Test Results
Screening tests are not considered a definite diagnosis. Those who come back with a positive screening test result will need to undergo additional testing to confirm a diagnosis of Krabbe disease. If confirmed, it is critical that families follow up immediately with a metabolic genetic specialist with experience in treating Krabbe disease.
Treatment
Treatment should be discussed with a metabolic genetic specialist with experience in treating Krabbe disease. The initial steps are determining if symptoms are present and if they are, what those symptoms are. If symptoms have not yet begun, decisions will need to be made regarding the possibility of having a hematopoietic stem cell transplant. If symptoms have already begun, a treatment plan will need to be developed by your healthcare team. Older children and adults who receive a diagnosis of Krabbe disease (with or without symptoms) will undergo a medical workup to see how far along the disease is. This workup will include various tests to inform the physician what parts of the body are affected and to what extent.
Support Groups
Support groups are important and can be a wonderful resource for families. Please look into the following support groups for Krabbe disease:
The Legacy of Angels Foundation
United Leukodystrophy Foundation
The Peace, Love, and Trevor Foundation
Questions? Comments? Need more information? Please contact the Emory Genetic Counseling Krabbe Disease team at (404) 778-0834 or lsd-gctc-l@listserv.cc.emory.edu