More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
Also known as: HLD6, TUBB4A-related leukodystrophy
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare genetic disorder characterized by abnormalities in myelin formation in the brain, specifically in the basal ganglia and cerebellum. It is caused by mutations in the TUBB4A or UFM1 gene, leading to progressive neurological symptoms, including movement impairments, muscle stiffness, ataxia, and intellectual disability. Treatment mainly focuses on managing symptoms and providing supportive care to enhance the individual’s quality of life.
A new diagnosis can be overwhelming as it brings unique challenges and adjustments, but it is important to remember that you are not alone.
Caused by mutations in the TUBB4A or UFM1 gene. They can be inherited but are typically the result of a sporadic mutation (new mutation, not inherited from their parents).
The TUBB4A gene is involved in forming microtubules, which give cells their shape. The gene is found most commonly in the central nervous system. When the gene is mutated, the formation and stability of microtubules is compromised, impairing the structure or function of cells in the central nervous system and causing the symptoms described.
The UFM1 gene is more recently discovered and is more common in the Roma population. The gene encodes ubiquitin-fold modifier 1 (UFM1), a ubiquitin-like (UBL) protein that has a wide range of functions.
Autosomal dominant – TUBB4A gene: In autosomal dominant conditions, only one copy of the genetic mutation is needed to cause the condition. We all have two copies of every gene, one from our mother and one from our father. Someone with an autosomal dominant condition has one parent with a copy of the genetic mutation and the condition themselves. Therefore, someone with an autosomal dominant condition has a genetic mutation on one copy of the gene from their parent with the condition. Each child of a parent with the genetic mutation will have a 50% chance of having the condition and a 50% chance of not having the condition.
Autosomal recessive – UFM1 gene: In autosomal recessive conditions, two copies of the genetic mutation are needed to cause the condition. We all have two copies of every gene, one from our mother and one from our father. The parents of someone with an autosomal recessive condition both carry one copy of the gene with a genetic mutation. Therefore, someone with an autosomal recessive condition has two copies of the genetic mutation, one copy from each parent. Each child of parents that both carry the genetic mutation will have a 25% chance of having the condition, a 50% chance of carrying the genetic mutation (like the parent), and a 25% chance of not having the condition.
Genetic counselling is essential for affected families due to the inheritance pattern of the condition. This is available at hospitals and Regional Genetic Centres. Please contact your doctor if you have any questions.
Learn more about genetic testing and counselling here.
Severity and progression of symptoms can vary, and may include learning difficulties, delayed motor development, spasticity, dystonia and hyperreflexia. Speech and swallowing problems may also develop, and it is also possible for those with H-ABC to develop hearing problems and nystagmus.
For those with the UFM1 gene, the MRI scan might show similar findings as H-ABC with unusual appearance of white matter. A significant proportion of patients have breathing difficulties (hypopnea, apneas), hypotonia, movement disorders (dystonia, dyskinetic movements), feeding difficulties and abnormal eye movements.
Learn more about specific symptoms of this leukodystrophy in these pages.
Although there is currently no specific treatment for this leukodystrophy, there is condition management information that may be useful for you in managing your or your loved one’s leukodystrophy.
There may be a current clinical trial, natural history study or patient registry for your condition. Check our current research page and ask your specialist doctor for more information.
We understand that research is a significant priority and source of hope for the leukodystrophy community. There is more research in leukodystrophy now than ever before. Alex TLC actively promotes and supports research in a number of ways.
Every month we update our database of research summaries with the most recent research. This includes summaries of leukodystrophy articles, clinical trials and pharmaceutical press releases. Our summaries allow our community to read about relevant recent research developments in a format that is easily understood.
Learn about the ways in which we can help in the how we support you section. When you or a family member been diagnosed with a leukodystrophy it may be difficult to know where to go for more advice – this information could help.
Our services and equipment section is here to help leukodystrophy patients and their families manage their condition. All information is based on our knowledge of UK services, however, our team are happy to receive support requests from other countries – email us.
You may be introduced to many different medical professionals which you may find confusing. View our guide to the health and care professionals you may encounter, with short descriptions about what they do.
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