Description of the condition

3-Methylglutaconic aciduria type 1 (MGCA1) is a rare genetic disorder caused by mutations in the AUH gene resulting in a build-up of amino acids in the fluids surrounding the brain and spinal cord. It is characterised by developmental delay, low blood sugar, abnormal muscle tone, loss of coordination, and optic atrophy. Symptoms can present in the neonatal period or adulthood but often diagnosis is later in childhood. Treatment primarily focuses on managing symptoms and providing supportive care.

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Cause

Caused by mutations in the AUH gene. This gene creates an enzyme 3-methylglutaconyl-CoA hydratase, it breaks down an amino acid to create energy. When the AUH gene is mutated, the amino acid is not broken down, creating an accumulation in the fluids surrounding the brain and spinal cord. Researchers think that this causes damage, leading to the symptoms described.

Inheritance

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.

This image shows the inheritance of genes from parents to their children and the resulting combination of genes the child will have. Red represents the genetic mutation, blue represents the normal copy of the gene. The line from each parent shows which gene they pass on to their child. The colours of the individuals tell the effect of the genes they have, red means they will be at risk of being affected, blue means they will not be at risk of being affected, and yellow means they carry the mutated gene.

Genetic counselling

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.

Symptoms

While symptoms may begin in the neonatal period, diagnosis of MGCA1 often happens later in childhood, following symptoms such as hypoglycaemiamicrocephaly, spastic quadriparesis, seizures, vomiting, hypotoniahepatomegalydystonia and progressive neurological deficit. Optic atrophy may occur, and severely affected individuals may become comatose.

Those who begin to experience MGCA1 in adulthood have symptoms such as dysarthria, ataxia, spasticity, optic atrophy and dementia.

More symptom information

Learn more about specific symptoms of this leukodystrophy in the pages listed here.

Treatments

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.

Current research

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.

Scientific research

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.

How we can support you

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.

How we support you

Services and equipment

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.

Services and equipment

Healthcare professionals

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.

Health and care professionals

Other resources

Links to useful information

We take great care in only selecting credible, useful links and resources, however we cannot be held responsible for the content of external websites or other sources.

View the full list of leukodystrophies