Also known as:
- GALC deficiency
- Galactocerebroside Beta-Galactosidase Deficiency
- Galactosylceramidase Deficiency
- Galactosylceramide Lipidosis
- Globoid Cell Leukodystrophy
- Sphingolipidosis, Krabbe’s Type
- Globoid Cell Leukoencephalopathy
Krabbe disease is due to a change, also known as a mutation, in a gene that encodes for an enzyme called galactocerebroside beta-galactosidase (GALC). This change means that the body does not create GALC properly, which is necessary for the production of myelin. Myelin is a protective material that surrounds the nerves. When there is not enough GALC to create myelin, a toxin is created instead which leads to the death of brain cells and nerves. Krabbe disease is associated with muscle stiffness, blindness, deafness, and eventually death. For some individuals with Krabbe disease, detecting it early and beginning treatment prior to the onset of symptoms may help to prevent some of the severe health outcomes associated with the condition.
Your baby’s doctor may ask you if your baby is showing any of the signs of Krabbe disease (see Early Signs below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.
If your baby’s newborn screening result for Krabbe disease was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your child to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, as a few babies do have the condition, it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of Krabbe disease can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.
Follow-up testing will involve checking your baby’s blood sample for the presence of the galactosylceramidase (GALC) enzyme in the white blood cells. If white blood cells appear to lack the GALC enzyme, it is highly likely that the child will have Krabbe disease. Other follow-up testing may include the following:
- CSF total protein test: the CSF total protein test detects the amount of certain proteins in the spinal fluid, or cerebrospinal fluid (CSF). A sample of the CSF is collected through a spinal tap, which is a small puncture to the lumbar spine, or the lower spine. If total protein levels are abnormally high, this is often indicative of Krabbe or other myelin- deficiency diseases.
- MRI of the head: This involves a magnetic resonance image (MRI) of the brain that encompasses the surrounding nerve tissue. This may determine if brain tissue has begun to deteriorate as a result of myelin absence.
- Nerve conduction velocity test: This test measures how fast a nerve impulse moves through nerve fibers. Electrode patches are placed on the skin on top of various nerves. These electrodes stimulate the nerve with a gentle electrical impulse. Other electrodes then pick up on this impulse and measure its velocity using the distance between the two electrodes and the time it took to travel between them. Slower nerve conduction velocity may indicate that the nerves have begun to deteriorate due to the lack of myelin coating.
- Genetic testing for the mutation in the GALC gene: Genetic testing can determine if an individual possesses the defect in the gene, and if they are at risk for passing it onto their children. This is often times performed on the parents of a child who received an abnormal newborn screening result. A blood test can be performed to detect the mutated gene in the parents. Prenatal tests such as amniocentesis or chorionic villus sampling can also screen for the presence of this disease in the developing baby.
About Krabbe disease
Signs of Krabbe disease can begin any time from infancy to childhood. Typically the signs do not become apparent until the baby is between two to six months of age. Up until then, a baby with Krabbe disease may appear to develop normally. There are two ways in which Krabbe disease can develop: early onset and later onset. Early onset of Krabbe disease leads to neurological deterioration, and death usually occurs before two years of age. The major symptoms of early-onset Krabbe disease are:
- Loss or underdevelopment of motor skills
- Muscle tone becomes floppy
- Hearing loss or sensitivity to loud noises
- Vision loss
- Lower weight or lower rate of weight gain than that of children similar in age, a condition known as “failure to thrive”
The early onset formof Krabbe has three stages that progress from general irritability, to deterioration of mental capabilities and muscle stiffness, and finally to complete blindness, deafness and eventually death.
The later onset type of Krabbe begins in childhood or early adulthood. These symptoms have a slower progression, and include vision problems, hearing loss and difficulty conducting basic movements. Muscle rigidity may also be present. The late onset form has variable conditions, and there is no definitive set of stages as there are with the early onset form. If your baby shows any of these signs, be sure to contact your baby’s health care provider immediately.
Unfortunately, there is no specific treatment or cure for Krabbe. Treatments do exist to improve the quality of life of individuals diagnosed with Krabbe. These may include medications to limit the frequency and severity of seizures, drugs such as benzodiazepines to manage irritability and muscle spasms, and physical therapy to slow the reduction of muscle tone.
Bone marrow transplant and umbilical cord blood stem cell transplant have been identified as possible treatments, and have been found to preserve cognitive function in some cases. These cases are varied, making it hard to evaluate the effectiveness of the treatment. Both forms of transplantation have been found to be most effective when conducted before the onset of symptoms. Since most infants may appear normal up until the onset of their symptoms, identifying the proper time to undergo transplantation is difficult.
Krabbe disease unfortunately has a poor prognosis for those babies who are diagnosed symptomatically: infants with early onset do not usually do not live to see the age of two. Those who develop it later in life may survive, but will suffer from nervous system disease. Complications involving the central nervous system may arise causing blindness, deafness and problems with muscle tone.
Krabbe disease is an inherited disease, due to a deletion in the galactosylceramidase (GALC) gene. It is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for the GALC enzyme, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition generally each carry one copy of the working gene, and one copy of the non-working gene. This means that they are carriers of the condition, but they typically do not show signs and symptoms of the condition. While having a child with Krabbe disease is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.
Support for Krabbe disease
Support groups can help connect families who have a child or other family member affected with Krabbe disease with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates.
Work with your baby’s health care provider to determine the next steps for your baby’s care. Your baby’s doctor may help you coordinate care with specialists who can help improve the quality of life for your child, such as physical therapists or counselors.
Because Krabbe disease is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for autosomal-recessive genetic conditions, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the National Coordinating Center for the Regional Genetic and Newborn Screening Service Collaboratives and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.
- The Hunter’s Hope Foundation website features biographies of many families who have had a child diagnosed with Krabbe disease, as well as the other Leukodystrophies.
- Madison’s foundation strives to directly connect parents whose children are diagnosed with the same or similar genetic disorders: