More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
Also known as: HLD1
Pelizaeus-Merzbacher Disease (PMD) is a rare genetic disorder caused by mutations in the PLP1 gene, which encodes a protein essential for myelin production, affecting the central nervous system. It is characterised by a lack of proper myelin formation, leading to progressive neurological symptoms, including developmental delay, intellectual disability, muscle weakness, tremors, and difficulty with coordination. Treatment primarily focuses on managing symptoms and providing supportive care to improve the affected individual’s quality of life. To note, there is also a condition called PMLD – Pelizaeus-Merzbacher-like Disease.
A new diagnosis can be overwhelming as it brings unique challenges and adjustments, but it is important to remember that you are not alone.
Pelizaeus-Merzbacher disease (PMD) is caused by mutations in the proteolipid protein gene (PLP1) which is on the X chromosome. This gene is responsible for the production of proteolipid protein which is one of the major components of myelin in the brain.
Mutations in the PLP1 gene sometimes cause progressive stiffness in the legs only (spastic paraparesis) without involvement of the brain.
X-linked Inheritance: The genetic mutation is located on the X chromosome. Men have one X and one Y chromosome while women have two X chromosomes. This means that a female with a mutated gene on one X chromosome, will be less affected because they have one working copy of the gene to compensate. However, a male with a genetic mutation on their X chromosome will be affected as they only have one copy of the gene. Men will always pass the gene to their daughters as men only have one X and not pass it to their sons as they pass on the Y to their sons.
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.
Usually, symptoms of Pelizaeus-Merzbacher disease appear in the first year of life with abnormal eye movements (nystagmus) or noisy breathing (stridor) often being present in the first month of life. Development is slow and abnormal motor development with stiffness, ataxia and abnormal movements develop. Epileptic seizures are common. Poor vision develops in many people.
Learning difficulties are common but is relatively less affected than the movement problems. Curvature of the spine (kyphoscoliosis) is common.
Development may slowly improve up to the age of 10 or 12 years but afterwards there is a very slow decline in physical and cognitive abilities with most people not living beyond mid adult years.
Mothers of boys with classical PMD may sometimes have symptoms such as walking difficulties, bladder problems or cognitive difficulties.
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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