More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
Also known as: Nasu Disease; Lipomembranous Osteodysplasia with Leukodystrophy; Polycystic Lipomembranous Osteodysplasia with sclerosing leukoencephalopathy (PLOSL)
Nasu-Hakola Disease (NHD) is a rare genetic disorder caused by mutations in the TREM2 or TYROBP genes, affecting microglia function, which are immune cells in the brain. It is characterized by progressive brain damage, including leukoencephalopathy (white matter abnormalities), leading to cognitive decline, behavioural abnormality, and movement difficulties. NHD also causes bone abnormalities and joint issues, such as fractures, cysts, pain and impaired mobility. Treatment primarily focuses on managing symptoms and providing supportive care.
A new diagnosis can be overwhelming as it brings unique challenges and adjustments, but it is important to remember that you are not alone.
Mutations in the TREM2 or TRYOBP gene (also called DAP12) cause Nasu-Hakola disease. Proteins produced by these genes help to replace old bone tissue with new bone, so mutations in the gene cause disruption in bone growth. These proteins also aid immune cells in the brain and spinal cord, although researchers are not yet sure how this leads to progressive neurological symptoms.
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.
NHD affects the bones and the brain progressively, with symptoms most commonly beginning between the ages of 20 and 30 with pain and tenderness in the feet and ankles. Fractures will become common in the following years, particularly in wrists, hands, ankles and feet as bones become weaker due to cyst-like changes and osteoporosis.
Symptoms relating to the brain usually begin in a person’s 30’s, although some experience these before bone-related symptoms. Personality changes are the first noticeable symptom, followed by loss of judgement and inhibition, poor concentration, periods of euphoria and epileptic seizures. Over time, this worsens into a loss of thinking and reasoning abilities and an inability to walk and talk. Those with Nasu-Hakola disease do not usually live past their forties.
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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