What is H-ABC?
Caused by a mutation in the TUBB4A gene, Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare genetic disorder that affects certain parts of the brain—specifically the basal ganglia and the cerebellum, which control movement. H-ABC targets these important structures, reducing both their size and function. As a result, those who suffer from H-ABC often experience motor problems.
H-ABC belongs to a group of 52 conditions called leukodystrophies, diseases that affect the white matter of the brain. These diseases disrupt the growth or maintenance of the myelin sheath, a protective layer that insulates nerve cells and allows for the transmission of messages between cells.
Myelination, the process of forming the myelin sheath, typically takes place in the first few years of life. In the case of H-ABC, hypomyelination occurs. This means that myelin isn’t produced at normal levels, which prevents the body from completing the process.
To get a better understanding of how leukodystrophies affect myelin, watch the video below.
Download “Living with Leukodystrophy”
Is H-ABC similar to MS?
H-ABC, and all leukodystrophies, do share some common features with multiple sclerosis (MS); however, they have different causes.
Whereas leukodystrophies are 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 immune system.
How many people have H-ABC?
As of 2019, fewer than 200 individual cases of H-ABC—the majority of which are children—have been identified. However, that number is on the rise.
What is the cause of H-ABC?
H-ABC is caused by a mutation in the TUBB4A gene.
Unlike other genetic disorders, H-ABC is usually not inherited from a parent. Instead, it typically emerges as a random mutation in the affected individual.
What are the symptoms of H-ABC?
The symptoms tied to H-ABC usually begin in infancy or early childhood and vary in severity.
Each child is affected differently; however, here are some examples:
Low muscle tone
Poor coordination
Speech problems
Difficulty eating
Involuntary movements
Rigidity
Deafness
Poor vision
Seizures
Muscle and limb stiffness
Learning difficulties
Attention problems
Loss of balance
Immobility (initial or over time)
How is this condition diagnosed?
A diagnosis for H-ABC is made based on the physical symptoms, brain imaging, and results of genetic testing.
Magnetic resonance imaging (MRI) of the brain is a key part of the process, as it can detect brain tissue patterns that are characteristic of H-ABC. However, genetic testing is the only means of confirming changes in the TUBB4A gene.
Is there a cure for H-ABC?
Currently, there is no known cure for this disabling and life-threatening condition.
For those affected by H-ABC, some treatments—physical therapy and certain medications, for example—may help alleviate symptoms and improve quality of life.
What is being done to find a cure?
Although H-ABC is most likely irreversible, the progression of the disease can be stopped. The good news is that research is currently underway.
Funding by the Foundation, Umass Chan Medical School is researching AAV gene therapy (adeno-associated virus), which is demonstrating very promising results. AAV is the transfer or addition of genetic material in cells to help treat a disease and is a type of genetic medicine. Once proof of efficacy is obtained, pre-clinical trials can begin.
Children's Hospital of Philadelphia (CHOP) is working with a biotech to advance ASO (antisense oligo-nucleotide), a treatment that develops short sequence of modified DNA, designed to bind to a problematic mRNA transcript and stop production of the disease-causing protein.
All of these therapies are very promising but unfortunately, the process to find a cure is lengthy, time-consuming, and costly.
This timeline can take five to ten years if all goes as planned, but the costs will be in the millions and the funding and level of attention given to this disease dictate the timeline. With our fundraising efforts, in conjunction with those of hospitals, and grants from various institutional sources, this can be accomplished, as it has been for other similar genetic conditions.