National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Hypomyelination with atrophy of basal ganglia and cerebellum

Back to List of Questions
My four-year-old daughter has been diagnosed with hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC).  It is apparently quite rare and we would like information on this condition.

The following information may help to address your question:


What is hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC)?

Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is a disease that affects certain parts of the brain. Symptoms usually begin in infancy or early childhood and worsen over time. Severity of symptoms and rate of progression can vary.[1] Symptoms may include delayed motor development, learning difficulties, upper-motor neuron dysfunction (spasticity, exaggerated reflexes, and Babinski signs), dystonia, rigidity, involuntary movements, and speech and swallowing problems.[1]

H-ABC is caused by a mutation in the TUBB4A gene. Inheritance is autosomal dominant, but most cases are due to a new mutation occurring for the first time in a person with the condition.[1][2]

Treatment may involve taking medications to ease symptoms, physical therapy, and surgery when dystonia does not improve with medication.[1]
Last updated: 5/15/2017

How might hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) be diagnosed?

H-ABC is diagnosed based on the presence of characteristic symptoms, a magnetic resonance imaging (MRI) scan of the brain, and genetic testing confirming a mutation in the TUBB4A gene.[1]
Last updated: 5/15/2017

What causes hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC)?

Hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC) is caused by a mutation in the TUBB4A gene. The mutation typically occurs for the first time in a person with the condition (i.e. it typically is not inherited from a parent).[2][1]

The TUBB4A gene is involved in the formation of microtubules. Microtubules are an important part of the cytoskeleton (which gives cells their shape). They also play important roles in many cellular processes such as cell division, motility, and transport. The TUBB4A gene is mostly expressed ("turned on") in the central nervous system (CNS), especially in parts of the brain affected by H-ABC. Mutations in this gene are thought to impair the formation or stability of microtubules. This in turn may impairs the structure or roles of cells in the CNS, leading to the signs and symptoms of H-ABC.[1]
Last updated: 5/15/2017

How might hypomelination with atrophy of basal ganglia and cerebellum (H-ABC) be treated?

Unfortunately, there is currently no cure for hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC). However, quality of life may be improved with management of individual symptoms of the condition, which may involve:
  • Medications and physical therapy for spasticity (e.g. baclofen, diazepam or intramuscular botulinum toxin)
  • Medications for dystonia (e.g. trihexyphenidyl, tetrabenazine, or high doses of levodopa and carbidopa which were reportedly helpful in case reports)
  • Gastrostomy for feeding for swallowing dysfunction
  • Routine treatment for seizures, constipation, and gastroesophageal reflux disease
Routine evaluations of swallowing and feeding, nutrition, orthopedic and joint integrity, and neurologic symptoms are recommended.[1]
Last updated: 5/15/2017

How rare is hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC)?

H-ABC is very rare. While the exact prevalence is unknown, as of 2016, 71 people with H-ABC have been reported.[1]
Last updated: 5/15/2017

We hope this information is helpful. We strongly recommend you discuss this information with your doctor. If you still have questions, please contact us.

Warm regards,
GARD Information Specialist

Please see our Disclaimer.

  1. Nahhas N, Conant A, Hamilton E, Curiel J, Simons C, van der Knaap M, Vanderver A. TUBB4A-Related Leukodystrophy. GeneReviews. November 3, 2016; https://www.ncbi.nlm.nih.gov/books/NBK395611/.
  2. Kniffin CL. Leukodystrophy, Hypomyelinating, 6; HLD6. OMIM. June 16, 2015; http://omim.org/entry/612438.