Globoid Cell Leukodystrophy

Globoid Cell Leukodystrophy (GLD)/Krabbe Disease

GLD is a rare genetic disorder where the enzyme galactocerebrosidase (GALC) is missing.  This results in a build up of globoid cells in the brain tissue.  Normally, nerve endings are covered with a myelin sheath which helps speed the communication of nerve impulses.  The globoid cells cause the myelin to break down, affecting the patient’s development.  As the disease progresses, the patient rapidly deteriorates.

Classic Krabbe Disease manifests itself in infants between three and six months old.  The child will develop normally until the onset of the disease, at which point parents will first begin to notice the child is extremely irritable.  “The bounds of the crankiness cannot fully be explained unless you have experienced it…..Our son cried for three days straight at one point and was hoarse for a week after,” stated one parent.  Other initial symptoms may include frequent fevers, difficulty keeping food down, stiffness in the limbs, and frequent seizures.  Eventually the child will become blind and paralyzed.  Most infants do not survive past the age of two.  There are two additional forms of the disease with slower rates of progression which are referred to as the juvenile and adult forms.  The juvenile form typically manifests itself after the 2nd birthday.  The onset of juvenile GLD is between 3 and 10 years with a duration of greater than 5 years.  The disease is typically characterized by decline in intelligence and motor skills, loss of vision, and difficulty walking.  The adult form has its onset in the teenage or adult years, often between 10 and 35 years of age.  It typically includes decreasing intelligence, neurological abnormalities, and loss of vision.

Because GLD is genetic, it is difficult to cure.  Current approaches to GLD include genetic counseling for parents who are carriers of the disease, and improvements in early detection of the disease in unborn children.  For GLD patients, a variety of treatments have been tried.  The goal of treatment is to get the missing GALC enzyme into the body. Unfortunately directly injecting it into the bloodstream has proven unsuccessful, since the enzyme cannot make it from there to the brain.  Injecting it directly into the brain has now worked either, because not enough of the enzyme is absorbed.

To introduce GALC into the body, both gene therapy and transplants are being used in clinical trials.  In gene therapy, researchers use a virus to place the gene that produces GALC into the patient’s cells.  Bone marrow or cord blood transplants are used to replace in the body bone marrow cells with the correct gene.  These marrow cells are able to travel to the brain much easier.  BMT can halt the progression of GLD if it has not progressed too far, but it cannot repair the existing damage.  Therefore, BMT is recommended for patients with disease in very early stage or who have a slower progressing form of GLD. It is possible that immediate BMT aftaer birth may help a child with the infantile form of this disease.  Much clinical research is being performed in this area.  For other patients, doctors treat the symptoms of the disease, using seizure control medication, physical therapy, and antibiotics to help the child become more healthy and comfortable.