inHypomyelination with Atrophy of Basal ganglia and Cerebellum (H-ABC) is a type of Leukodystrophy that affects certain parts of the brain. The Leukodystrophies make up a group of rare genetic disorders that affect the central nervous system by disrupting the growth or maintenance of the myelin sheath, which insulates nerve cells. These disorders are progressive, meaning that they tend to worsen throughout the life of the patient. The leukodystrophies do share some common features with multiple sclerosis (MS). Like the leukodystrophies, MS is caused by the loss of myelin from the axons; however, the cause is different. Whereas leukodystrophies are generally caused by a defect in one of the genes involved with the growth or maintenance of the myelin, MS is thought to be caused by an attack on the myelin by the body’s own immune system. There ate 52 different types of leukodystrophies including H-ABC.
Symptoms tied to H-ABC usually begin in infancy or early childhood and vary in severity; they include movement difficulties and delay in mental development or learning problems. These symptoms occur because certain brain cells in individuals with H-ABC are not fully covered by myelin (hypomyelination), a substance that usually surrounds nerve cells to help them work better. Also, this condition causes the breakdown (atrophy) of two parts of the brain that help to coordinate movement - the basal ganglia and cerebellum. H-ABC is caused by a mutation in the TUBB4A gene. The mutation usually occurs for the first time in a family as a result of a new mutation in the affected individual. The mutation is rarely inherited from a parent. The disease presents itself in different ways and progresses at varying rates, but gross and fine motor functions, as well as speech are initially affected, and later other body functions are impaired by the muscular functions. This disease is progressive in nature.
Hypomyelination with atrophy of basal ganglia and cerebellum is very rare. In fact, many doctors don't know about it much less what it is. As of 2016, less than 100 individuals with this condition have been identified. However, this number is growing quickly, largely due to its recent discovery. Unfortunately, at this time, there is no known cure. The good news is that research is currently underway, Dr. Vanderver, now at Children's Hospital of Philadelphia (CHOP) has already started exploring gene therapy, which is the wave for the future in curing many cellular level diseases. The process to find a cure is lengthy, time consuming and costly. Currently, cellular level research of the disease is complete. Next is to research the biological make up of the disease in infected mice to better understand the disease in a living animal. Yale University is partnering with CHOP along with the University of Pittsburg working on this next stage of the research. This allows the team to accurately target the best approach for the gene therapy with the ultimate objective to find and replace/destroy the defective protein in the gene. Once concluded, the next stage is to obtain FDA approval and then go to clinical trial, a lengthy process. This timeline can take up to five years if all goes as planned but the costs will be in the millions. With our fundraising efforts and in conjunction with the hospital, grants from various institutional sources, this can be accomplished as seen for other similar genetic conditions (GAN is an example).
We have recently branched our efforts out further to seek funding to help provide families with needed equipment and services. Due to the rareness of this disease, the lack of awareness also means lack of understanding. Many families struggle to obtain basic equipment and services for children to enjoy their life to the fullest, such as a wheelchair or physical therapy, something most children don't even have to think about.
Click below to learn more about Dr. Vanderver's research to date at Children's National Medical Center, which has now been transferred to Children's Hospital of Philadelphia (CHOP).