More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
Hypomyelinating leukodystrophies (HLD) are a group of rare genetic disorders caused by mutations in several different genes characterised by reduced or abnormal myelin in the central nervous system (CNS). It leads to the progressive degeneration of the brain’s white matter, causing neurological symptoms such as developmental delay, movement difficulties, seizures, visual problems, and learning or intellectual difficulties. Treatment currently 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.
Hypomyelinating leukodystrophies are caused by pathogenic variants in a wide range of genes involved in myelin development and maintenance. Myelin is the protective covering of the nerve fibres that allows efficient transmission of nerve signals. When myelin formation is insufficient or defective, communication between nerve cells is impaired, leading to a range of neurological problems.
Currently, around 40 different genes are known to be associated with HLD, and the number continues to expand as genetic research advances.
A full list of genes can be found here.
Autosomal recessive: 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.
The clinical presentation of HLD can be different for every person. Symptoms can begin in infancy, childhood, or occasionally adulthood, and disease progression varies widely between conditions and individuals. The clinical course is highly variable. Some conditions progress slowly, whereas others progress more rapidly with a less favourable outcome. In few specific conditions, partial or spontaneous clinical improvement has been described.
The most common features include motor impairment (abnormal tone, spasticity, ataxia), visual disturbances, and cognitive and learning difficulties. Additional difficulties, that might develop includes speech and swallowing difficulties, epileptic seizures (not so common), and hearing difficulties. In many hypomyelinating leukodystrophies organs outside the nervous system may also be affected, as the underlying genes often play roles in important cellular processes expressed in multiple tissues. For this reason, a comprehensive multisystem assessment is essential.
Management
At present, there are no disease-modifying treatments for hypomyelinating leukodystrophies. Importantly, advances in genetic understanding and therapeutic development have led to emerging targeted treatments, with several drug candidates now entering clinical trials for specific HLD. Families should be informed about ongoing research and, where appropriate, opportunities for trial participation.
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 are 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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