More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited metabolic disorder characterised by the accumulation of L-2-hydroxyglutaric acid in the brain and other tissues. It is caused by mutations in the L2HGDH gene, leading to a deficiency of the enzyme L-2-hydroxyglutarate dehydrogenase. Symptoms typically appear during early childhood and include developmental delay, seizures, movement abnormalities, and progressive neurological deterioration. Treatment mainly focuses on managing symptoms and providing supportive care to enhance the affected 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 L2HGDH gene. This gene makes an enzyme found in mitochondria which breaks down a compound in order to produce energy. Mutations cause a shortage in this enzyme, allowing the compound to build up. This can damage and destroy cells, with brain cells appearing to be the most vulnerable to this.
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.
There are three major types of 2-hydroxyglutaric aciduria, a condition causing progressive brain damage; D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA).
D-2-hydroxyglutaric aciduria affects muscle movement, speech, vision, emotion, thinking and memory. Delayed development, seizures, and weak muscle tone are other symptoms.
So far, D-2-HGA is associated with more of grey matter involvement and other system involvement. From our knowledge, currently we think L-2 HGA affects white matter more than grey matter.
L-2-hydroxyglutaric aciduria symptoms include progressive brain damage, developmental delay, speech difficulties, seizures and macrocephaly. Problems with balance and muscle coordination are also common. By early adulthood, those with this condition will have severe disability.
The combined type D,L-2- hydroxyglutaric aciduria, causes severe brain abnormalities. Symptoms include severe seizures, weak muscle tone, breathing and feeding difficulties. Those with the combined type rarely survive past early childhood.
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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