Krabbe Disease
Toxic build-up = damaged nerve cells
Overview
Krabbe disease is a rare, genetic, incurable, terminal disorder. It is one of several known leukodystrophies: genetic diseases that progressively destroy the white matter of the brain.
In Krabbe disease, the enzyme galactocerebralcidase (GALC), which is essential for metabolizing several important compounds in the body, is deficient. Therefore, substances which should be broken down and naturally released from the body start to accumulate. This toxic build-up damages the central nervous system, particularly destroying the myelin sheath, which insulates the nerves. The destruction of the myelin sheath, called demyelination, impedes the conduction of nerve signals from the brain to the rest of the body. As the myelin degrades, it causes physical disabilities (mental abilities are not hindered because the grey matter of the brain is unaffected).
Judson's Form of Krabbe
It is estimated that Krabbe disease affects approximately 1 out of every 100,000-200,000 people worldwide. 90% of these cases are early-infantile Krabbe, in which symptoms begin between 3-6 months of age. These babies quickly stop developing normally and usually die before the age of two.
However, Judson had late-onset Krabbe; this rare form of the disease affects 1 in every couple million children. He experienced completely normal development for the first years of his life, then just before age 2 1/2 the toxic build-up in his system triggered the onset of symptoms. This type of Krabbe generally progresses more slowly than the early-infantile form. Yet, Judson had a rapidly fatal form of the disease, challenging previous research by doctors. He died just 5 months after his brain began demyelinating.
Judson's Symptoms
Judson's symptoms began with irritability, lack of balance resulting in stumbling, vision impairment, and diminished behavioral control of impulses. These initial concerns quickly lead to an inability to walk, blindness, and difficulty sleeping. The disease progressed so rapidly that we could actually observe deterioration in Jud's system from day to day.
Just 3-4 months after onset, Judson's whole body was completely paralyzed, including muscle weakness which left him unable to even hold up neck. Furthermore, he became not only blind but also mute, his swallowing reflex diminished, he had impaired bowel function, and experienced severe spasticity in his arms and legs. Ultimately, Judson died when the critical functions in his body shut down, including his ability to breathe.
Despite being plagued with these horrendous disabilities, we are thankful that Jud's mind was clearly unaffected, and he never experienced diminished auditory capabilities. He found great pleasure using his imagination!
Judson maintained tremendous joy throughout his suffering, apparent in his amazing smile and laughter that continued to melt hearts until just days before he passed away.
Judson's Diagnosis
After an emergency MRI that indicated damage in the white matter of Jud's brain, the Levasheffs rode the roller coaster of incorrect diagnoses. Further tests included an MR Spectroscopy, blood and urine lab work, a spinal tap that indicated increased levels of protein, and finally a specialized blood test for enzyme deficiencies.
When the GALC deficiency was detected in Judson's blood, the diagnosis of Krabbe disease was confirmed by having Drake and Christina's blood also tested for GALC enzyme levels and gene mutations. The results were consistent with the diagnosis, signifying that both Drake and Christina were carriers of Krabbe disease (information that was previously unknown to each of them).
Judson's Treatment
Seeing as there is currently no cure for Krabbe disease or major recommended treatment once the deterioration is in full swing, Judson was immediately placed on hospice care. His disease-management consisted of physical and occupational therapy to minimize discomfort and attempt to improve his quality of life despite his increasing disability. In Judson's last weeks, drugs were administered for pain control and to reduce spasticity in his arms and legs.
Though Judson's form of Krabbe rapidly destroyed his body, it should be noted that for individuals who are diagnosed before symptoms begin or after symptoms start but they progress slowly, there is the possibility for stem cell transplantation as treatment. Although this is not a cure, the transplant adds normal-functioning cells to the body which can help produce the GALC enzyme and hopefully inhibit the affects of the disease.
Krabbe & Siblings
Krabbe disease is inherited in an autosomal recessive pattern. Since both Drake and Christina are carriers of Krabbe-causing gene mutations, there was at least 25% likelihood that Jessie had Krabbe disease as well. Fortunately, her blood tests revealed that she is simply a carrier of the disease (50 % chance). Were Drake and Christina to conceive more children, their offspring would have a 25% genetic possibility of being afflicted with Krabbe disease.
Current Krabbe Research
Along with stem cell transplantation, researchers are investigating therapies which would replace the missing GALC enzyme, and gene therapy which substitutes defective genes with normal-functioning genes. In addition, people with Krabbe disease would benefit from scientific advances toward re-myelination of the brain.
Newborn Screening
A newborn screening test, using the few drops of blood obtained in the hospital from the required heel prick, can detect Krabbe disease early in a baby's life, providing the possibility for treatment, such as stem cell transplant, before the onset of symptoms.
Judson was born in California where they do not currently screen for Krabbe disease, however, the state of New York automatically screens for Krabbe. Although every child born in the USA receives a newborn screening test, the actual diseases for which it screens vary from state to state. The Secretary's Advisory Committee for Heritable Disorders recommends 54 diseases for screening, but only a couple states in the nation currently screen for all the recommended diseases. Universal Newborn Screening (UNBS) advocates for every state to test for all the recommended diseases.
Just like Judson, a baby can appear healthy at birth and even for several years, yet, in fact, have a devastating disorder. Some of these diseases only require a simple change in diet to ensure a healthy, full life for the child, yet without the newborn screen they will likely face severe morbidity and even death.
What are the diseases your state screens for?
If you or someone you know is pregnant, you can order a supplemental screening kit to be used in the hospital when the baby is born. Click here for more information and to order a kit.
More Information About Krabbe Disease
If you are interested in more information and current research about Krabbe disease, please visit the following organizations: