MELAS syndrome, MIDD and the m.3243A>G mutation

This page covers the full spectrum of mitochondrial conditions associated with the m.3243A>G mitochondrial DNA variant, including MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes) and MIDD (Maternally Inherited Diabetes and Deafness). Although it might sound complicated, m.3243A>G simply refers to the location where the genetic change has occurred in the mitochondrial DNA.

The m.3243A>G variant is one of the most common genetic causes of mitochondrial disease, and symptoms can vary widely. While some individuals develop the features of MELAS syndrome, fewer than 10% of people with this variant will experience stroke-like episodes. Many more develop diabetes, hearing loss or milder muscle symptoms (MIDD), and some may have very few or no symptoms at all.

What causes MELAS disease, MIDD and m.3243A>G-related mitochondrial disease?

The m.3243A>G change affects how mitochondria convert food into usable energy. Because mitochondria are crucial to the function of energy‑dependent cells, this variant can lead to a range of symptoms affecting the muscles, brain, ears, pancreas and other organs.

The same genetic change can produce different symptoms in different people, even within the same family. Factors such as the proportion of affected mitochondria (heteroplasmy) and which organs carry higher levels of the variant help explain this variability.

This is why m.3243A>G is now understood as causing a spectrum of possible conditions, including:

• MELAS – typically involving neurological symptoms and stroke‑like episodes.
• MIDD – diabetes and progressive hearing loss.
• Muscle symptoms, such as weakness and fatigue.
• Other features such as short stature, headaches or cardiac involvement.

What is MELAS syndrome and what are the symptoms?

MELAS is one of the recognised presentations associated with the m.3243A>G variant. It can cause:

• Stroke‑like episodes – sudden changes in movement, speech or vision not caused by a typical stroke. These are often accompanied by confusion, altered awareness or sometime hallucinations. (True strokes are caused by problems with the blood supply to the brain whereas stroke-like episodes happen when the brain is unable to generate energy at a particular site, causing brain cells to fail. They have different appearances on brain scans.)
• Seizures or epilepsy.
• Severe or recurrent headaches.
• Memory or concentration problems.
• Severe gut problems.

Muscle involvement may include:

• Muscle weakness.
• Exercise intolerance.
• Muscle pain or cramps.

MELAS disease most often appears in childhood or early adulthood. However, it’s important to emphasise that MELAS is not the most common presentation of the m.3243A>G variant.

What does MELAS stand for?

MELAS stands for Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like Episodes. It’s caused by genetic changes that affect how the body’s cells make and use energy, particularly in the brain and muscles.

What is MIDD disease and what are the symptoms?

Many individuals with the m.3243A>G variant first present with features of MIDD, or Maternally Inherited Diabetes and Deafness, which may include:

• Diabetes, often in adolescence or adulthood.
• Sensorineural hearing loss, usually progressive and affecting both ears.

Some people with MIDD may also experience:

• Mild muscle symptoms.
• Short stature.
• Gastrointestinal difficulties.

What does MIDD stand for?

MIDD stands for Maternally Inherited Diabetes and Deafness. Patients affected by this form of mitochondrial disease don’t suffer stroke-like episodes, unlike with MELAS.

What are the symptoms of mitochondrial disease m.3243A>G?

Other symptoms of the m.3243A>G mutation can differ greatly from person to person and may include:

• Muscle weakness or fatigue.
• Migraines or recurrent headaches.
• Balance difficulties.
• Heart rhythm problems or cardiomyopathy.
• Visual problems.
• Lactic acidosis in blood tests.
• Gastrointestinal symptoms.
• Chronic Progressive External Ophthalmoplegia (CPEO).

Some individuals remain only mildly affected.

How are MELAS syndrome, MIDD and m.3243A>G-related disease diagnosed?

Diagnosis may involve:

• Genetic testing of blood, urine or muscle.
• Brain imaging, particularly if neurological symptoms are present.
• Blood and urine tests, including lactate levels.
• Hearing and eye assessments.
• Muscle biopsy, in selected cases.

In the UK, diagnosis and ongoing care are led by the NHS Highly Specialised Services for Mitochondrial Disorders, offering access to expert multidisciplinary teams.

Are there any MIDD, m.3243A>G-related disease and MELAS treatments?

As with all mitochondrial diseases, there is no cure for MELAS disease, MIDD disease or m.3243A>G‑related disease. Management focuses on:

• Treating symptoms.
• Supporting organ function.
• Reducing complications.
• Improving quality of life.

Current MELAS treatment plans may include:

• Diabetes care and blood sugar monitoring.
• Hearing support, including hearing aids or cochlear implants.
• Anti‑seizure medicines for epilepsy.
• Physiotherapy, occupational therapy and tailored exercise advice.
• Speech and language therapy.
• Nutritional guidance.

During stroke‑like episodes associated with MELAS syndrome, hospital treatment may be required to manage symptoms and prevent further complications.

Is there any mitochondrial research underway into this mutation?

Research continues to explore why symptoms vary so widely between individuals with the m.3243A>G variant and how best to predict and manage complications. Studies are also investigating potential new treatments that may support mitochondrial energy production. Details of current clinical trial opportunities can be found on the UK trials and research studies page of our website.

The Lily Foundation plays an active role in representing patients and families in research discussions and supporting the development of future care guidelines.

Is there any support for people with m.3243A>G disease, MELAS or MIDD syndrome?

In the UK, specialist care for all forms of mitochondrial disease is provided through the NHS Highly Specialised Services for Mitochondrial Disorders, offering diagnosis, care management and family support.

The Lily Foundation understands the challenges around living with a diagnosis of any type of mitochondrial disease. We exist to provide emotional support, practical guidance and advocacy for patients and families.

As well as this, we invest in research to improve understanding of mitochondrial disease and to drive the development of new treatments for the future.

If you or someone you love has recently been diagnosed with an m.3243A>G-related mitochondrial disease, visit our mitochondrial disease Q&A page for further information, or contact our support team to connect with others who understand.