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)
Screening Tests for Krabbe Disease
Screening for Krabbe disease is now part of the routine Georgia Newborn Screen performed on every child after birth. If your child has a positive screen for Krabbe disease, you will be contacted immediately by the Newborn Screening Follow Up program or by a medical specialist.
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