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


Other Names:
H-ABC; Leukodystrophy, hypomyelinating, 6; HLD6; H-ABC; Leukodystrophy, hypomyelinating, 6; HLD6; Leukodystrophy, hypomyelinating, with atrophy of the basal ganglia and cerebellum; HABC See More
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This disease is grouped under:
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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Percent of people who have these symptoms is not available through HPO
Ataxia 0001251
Autosomal dominant inheritance 0000006
Autosomal recessive inheritance 0000007
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral hypomyelination 0006808
Choreoathetosis 0001266
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Dysarthria
Difficulty articulating speech
0001260
Dystonia 0001332
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Leukodystrophy 0002415
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Motor delay 0001270
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Optic atrophy 0000648
Poor speech 0002465
Progressive
Worsens with time
0003676
Rigidity
Muscle rigidity
0002063
Seizure 0001250
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Specific learning disability 0001328
Sporadic
No previous family history
0003745
Tremor 0001337
Variable expressivity 0003828
Visual impairment
Impaired vision
Loss of eyesight
Poor vision
[ more ] 		0000505
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Last updated: 7/1/2020
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
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

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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
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

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.
  • Orphanet lists European clinical trials, research studies, and patient registries enrolling people with this condition. 

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Hypomyelination with atrophy of basal ganglia and cerebellum. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Hypomyelination with atrophy of basal ganglia and cerebellum:
    Myelin Disorders Bioregistry Project
     

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Organizations Providing General Support

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Hypomyelination with atrophy of basal ganglia and cerebellum. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • 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. See answer


  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.