MELAS - Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes

Research often describes MELAS as the most common type of mito and the most common mitochondrial encephalomyopathy.^11,15–17 But this refers to how often it appears among people with mito, not the general population. Overall, MELAS is still considered rare.^15,18,19

The genetic change most often linked to MELAS (m.3243A>G)  is more common than the condition itself. Many people who carry this change have only mild or no symptoms.^15,18,19

In a large study of 1,351 people with mito in China, MELAS was the most common type of mito, making up 45% of cases. However, this was within the mito population, not the general public.¹⁵

MELAS is a multisystem condition that can present differently in different people.

The main signs and symptoms are:

Lactic acidosis

Lactic acid is made by your cells when your body doesn’t have enough oxygen. This can happen during strenuous exercise, illness, or when cells can’t use energy properly, like in mito.

When this happens, your body switches to a backup system called anaerobic metabolism, which makes extra lactic acid. If too much lactate builds up, or your body can’t clear it properly, it can lead to lactic acidosis.

High levels of lactic acid in the blood can be harmful if not managed.

Read more about lactic acidosis.

Stroke-like episodes.

Stroke-like episodes can affect the brain, muscles, and nervous system. They may look like a stroke but are not caused by a blocked blood vessel.

These episodes can cause:

• Sudden weakness on one side of the body
• Confusion or loss of awareness
• Vision or hearing loss
• Problems with thinking or memory
• Hallucinations

Other signs may include:

• High levels of lactic acid, associated with vomiting, tiredness, muscle weakness, and trouble breathing

Stroke-like episodes are serious and need emergency care right away. Early treatment can help reduce the risk of long-term damage.

Seizures

Seizures happen when there is sudden, unusual activity in the brain.

Seizures can cause:

• Shaking or jerking movements
• Muscle stiffness
• Staring spells
• Loss of awareness

Seizures may happen on their own or during a stroke-like episode. They can vary in how serious they are and may need long-term treatment to manage.

Muscle weakness (myopathy) and exercise intolerance

Many people with MELAS have muscle weakness and can feel very tired after even light activity.

This can lead to:

• Trouble walking or lifting objects
• Shortness of breath during activity
• Needing more rest than usual

This happens because mitochondria can’t produce enough energy. Pacing, rest, and gentle activity can help manage these symptoms.

Learn more about exercise and mito

Progressive cognitive decline

MELAS can cause gradual changes in how the brain works over time.

This may affect:

• Memory and thinking
• Speech or language
• Movement and coordination
• Mood and behaviour

These changes can happen slowly and may get worse with more stroke-like episodes.

Sensorineural hearing loss

Hearing loss usually affects both ears and gets worse over time.

This happens because of damage to:

• The inner ear
• The nerve that sends sound to the brain

This type of hearing loss is permanent, and hearing aids or other devices, including cochlear implants, may help.

Diabetes

Some people with MELAS develop diabetes, often in their teens or early adult years.

This happens when the body:

• Doesn’t make enough insulin
• Can’t use insulin properly

Diabetes in MELAS is managed like other types of diabetes, through diet, exercise, and sometimes medication or insulin.

Learn more about diabetes and mito

Other signs and symptoms

Include:

• Visual impairment
• Migraines
• Cardiomyopathy (large heart)
• Ataxia (unsteadiness)
• Short stature
• Failure to thrive
• Autism spectrum disorders
• Mental health disorders, such as depression and bipolar disorder

This section combines information from trusted sources.^1,4,9,23-24 The explanations have been adapted into plain language by Mito Foundation to support understanding within the mito community.

For more information

Understand the signs and symptoms of mito

MELAS is a genetic condition caused by genetic changes that affect the mitochondria. Our cells rely on mitochondria to turn food into energy and remove waste.

In MELAS, a genetic change affects how mitochondria produce energy. When energy levels are too low, cells can become damaged or stop working properly. This can impact parts of the body that need a lot of energy, like the brain and muscles.

Low energy production can also lead to a build-up of lactic acid and other waste products in the body. This may cause symptoms such as seizures, muscle weakness, and stroke-like episodes.

The genetic cause

MELAS is most often caused by changes in mtDNA, which is passed down from the mother. A person may carry this genetic change without having symptoms, and not everyone with the change develops MELAS.¹¹

The most common genetic change is found in the gene called MT-TL1,⁴ which makes a molecule called tRNA Leu (UUR). This molecule helps build proteins that mitochondria need to make energy.

The most common change is when an “adenine” (A) changes to a “guanine” (G) at a specific point in the mtDNA. This change is called m.3243A>G. About 80% of people with MELAS have this genetic change.^4,25,26

Figure 1: Explanation of the common genetic change for MELAS. The most common genetic change that causes MELAS is found in the mtDNA genome (m), affecting a specific point in the MT-TL1 gene (.3243), with the sequence of letters changed from A to G (A>G).

The MT-TL1 gene contains instructions to make a molecule called transfer RNA (tRNA). You can think of tRNA as a tiny courier — it collects protein building blocks (amino acids) and delivers them to where proteins are made in the cell. MT-TL1 makes a specific type of tRNA called tRNA Leu (UUR), which delivers the amino acid leucine to help mitochondria build the proteins they need for energy.²⁷

Another genetic change linked to MELAS is found in the MT-ND5 gene, known as m.13094T>C. This change is seen in about 20% of people with MELAS.²⁵

Changes in these genes affect how mitochondria produce energy. When energy levels are too low, lactic acid can build up, and symptoms like seizures and stroke-like episodes can occur.

Nuclear DNA changes

While most cases of MELAS are linked to changes in mtDNA, some are caused by changes in nuclear DNA (nDNA), the DNA found in the cell’s nucleus.

A large study of 1351 people with mito in China found that 16.5% had changes in nuclear genes, with POLG being the most common. POLG provides instructions for making a protein that helps mitochondria copy and repair their DNA.

Although MELAS caused by POLG is rare, this study shows it’s an important part of the wider genetic picture, especially when mtDNA changes aren’t found.¹⁵

Other genes that may cause MELAS

While most people with MELAS have changes in the MT-TL1 or MT-ND5 genes, other genes can also be involved. These genes help make molecules that support protein building or energy production in mitochondria.

Some genes help build tRNA, which delivers amino acids (the building blocks of proteins):

• MT-TC – carries cysteine
• MT-TF – carries phenylalanine
• MT-TH – carries histidine
• MT-TK – carries lysine
• MT-TL2 – carries leucine
• MT-TQ – carries glutamine
• MT-TV – carries valine
• MT-TW – carries tryptophan
• MT-TS1 and MT-TS2 – both carry serine

Other genes help mitochondria make energy:

• MT-ND1 and MT-ND6 – part of the energy-making machinery
• MT-CO2 and MT-CO3 – involved in how cells use oxygen
• MT-CYB – supports energy production in cells

These genetic changes are much less common but can still cause MELAS.^4,28

Genetic carriers

Each cell in your body contains many mitochondria, but not all are the same. Some may work well, while others carry genetic changes. This mix is called heteroplasmy.

You can think of it as having a mix of working and faulty machinery. If enough of the faulty machinery builds up in a cell, it can lead to symptoms. But if there are still enough healthy mitochondria, a person might not have any signs.

This uneven mix means that:

• Symptoms can vary within a family
• MELAS can skip a generation
• Different organs may be affected in different ways.

A mother can carry the genetic change that causes MELAS but show no symptoms herself. In this case, she is called a genetic carrier. All her children are at risk of inheriting the change, but the effects can differ from person to person. Some may develop symptoms; others may not.

It’s difficult to predict who will be affected and how severely. Testing for MELAS before birth is also complex because of the way mtDNA is passed down.

MtDNA is passed down from the mother. This means a father with a mtDNA genetic change linked to MELAS can’t pass it on to his children. Only mothers can pass on mtDNA changes.

For more information

Learn more about genetics and mito

Information to understand your diagnosis

Information to understand your child’s diagnosis

Diagnosing MELAS is based on your medical history, signs and symptoms, a physical examination, and other specialist tests.

Physical exam

A health professional will check for signs that may suggest MELAS. This can include:

• Stroke-like episodes
• Seizures or other neurological symptoms
• Muscle weakness
• Vision or hearing changes
• Balance or coordination difficulties

Other tests may include:

• Blood or spinal fluid tests

These check for high levels of lactate and pyruvate, which can be signs of MELAS.

• Brain scans (MRI or CT)

Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) look for changes in the brain that may suggest stroke-like episodes or other signs linked to MELAS.

• Heart tests

An electrocardiogram (ECG) checks your heart rhythm. An echocardiogram (echo) may be used to look at the heart muscle.

• Muscle biopsy

A small sample of muscle is checked under a microscope. A finding called "ragged red fibres" may be seen in some people with MELAS.²⁹

Genetic testing

If your doctor suspects MELAS, they will arrange genetic testing to look for any changes associated with the condition. The genetic change for MELAS is found in DNA. This is usually in the form of a blood or saliva sample. But sometimes, other samples like skin, hair, urine, or muscle are needed to test heteroplasmy (see causes of MELAS).

Genetic testing is highly specialised, and it may take up to three to four months to receive the results. Genetic counselling is important to discuss what these results mean for you and your family.

For more information

Learn more about genetics and mito

If you have MELAS, you’ll likely need a team of health professionals to manage your care. Here are some health professionals you might work with:

• General Practitioner (GP): your main point of contact. They can help with referrals, tests, and coordinate your care.
• Neurologist: specialises in nervous system disorders, including stroke-like episodes.
• Endocrinologist: to address any metabolic or endocrine abnormalities, such as diabetes.
• Metabolic specialist: helps manage energy production issues, ensuring the cells get the energy they need to function.
• Gastroenterologist: addresses digestive problems, including feeding difficulties and gastrointestinal symptoms.
• Cardiologist: accesses and monitors heart conditions.
• Audiologist: assesses and monitors with hearing loss.
• Genetic Counsellor: provides education and support for people with genetic health conditions.
• Physiotherapist: to help maintain muscle strength and mobility.
• Occupational Therapist: assists with daily living activities and maintaining quality of life.
• Mental health professional: offers mental health and wellbeing support.

For more information

Information to build your care team

Information to build your child’s care team

For most people with mito, regular tests are important. These tests help monitor how mito is affecting you. Learn more about monitoring mito for adults, or children.

The following recommendations have been adapted from the Australian Patient Care Standards for mito.³⁰

Watching for serious illness (Critical care)

During a sudden illness, your lactate levels should be closely monitored. Lactate levels refer to the amount of lactic acid in your blood. Elevated levels of lactic acid can be harmful. But, monitoring the lactic acid in your blood (serum lactate) can help your health care team intervene early, to reduce the risk of series illness.

If you are treated with L-arginine, assessments of your blood levels are needed. L-arginine is thought to improve blood flow to the brain in people with MELAS. So monitoring is needed to ensure the L-arginine level remains at the right level, known as therapeutic level.

A bowel pseudo-obstruction is when your bowel becomes paralysed, and your body acts as if something is obstructing your bowels. Signs and symptoms include abdominal distension, pain, loss of appetite, nausea, and constipation or diarrhoea. If you experience pseudo-obstruction, it should be treated urgently in a hospital. During this time, it is recommended that you don’t eat or drink but instead receive hydration intravenously (through your vein).

In case of muscle breakdown due to exercise or illness, known as rhabdomyolysis, there are standard treatments to follow. You should present to the hospital if you are very unwell and have dark-coloured urine.

Growth and hormone care (Endocrinology)

Diabetes, formally known as diabetes mellitus, is more common in people with MELAS, than other types of mito. It is important to manage your blood sugar within your target range. This will help prevent nerve damage and other diabetic-associated conditions.

Brain and nerve care (Neurology)

If you experience migraines, it is recommended that they be treated similarly to someone without MELAS. But it is important to know that treatments such as valproate may be harmful (contraindicated). Your health professional may consider L-arginine to help manage migraines or headaches.

Muscle weakness (Myopathy)

Your muscle function may be evaluated, including strength and certain enzyme levels. Monitor any changes or worsening of symptoms. If you notice any changes, speak to your health professional. They may request blood tests to look for high levels of enzymes or look for other potential causes, which might involve a range of tests.

Exercise is beneficial, but it should be tailored to your needs and capabilities. Before starting any exercise program, your heart function should be checked to ensure it’s safe to proceed.

Certain medications for high cholesterol (statins), blood sugar control (metformin), asthma (corticosteroids), and medications to treat viral infections such as HIV (antiretrovirals) can affect your muscles. They should be used with caution. If you’re prescribed these, regular monitoring is crucial to avoid worsening your myopathy.

Supplements like co-enzyme Q10 and riboflavin might be recommended depending on the specific deficiencies associated with your condition.

When managing myopathy as part of mito, it’s essential to be proactive about your health. It’s always best to discuss these aspects with your health professional to get advice that fits your situation. They can guide you on the right path to managing your condition effectively.

Heart care (Cardiology)

You may need an initial heart check-up, including an ECG, 24-hour ECG monitoring, and an echocardiogram. Annual ECGs monitor your heart health. The frequency of other tests will be personalised based on your specific needs and family history.

Hearing care (Audiology)

Regular hearing checks are essential, especially for children who might need special tests. These assessments should be done initially and then every one to two years. Avoid loud noises to prevent worsening hearing loss, which might not be reversible. Some antibiotics, like aminoglycosides, can worsen hearing loss.

Monitor your hearing closely during serious illnesses or acute episodes. Digital hearing aids can help with moderate to severe hearing loss, while cochlear implants might be an option for very severe cases. Talk to your health professional about these options. Hearing loss can affect speech and learning, especially in children.

Looking after your mental health (Psychology)

Taking care of your mental health is as important as managing physical symptoms when dealing with MELAS. If you have any psychiatric symptoms, such as anxiety, depression or memory loss, speak to your health professional.

For children, it’s particularly important to watch for low self-esteem and anxiety. Addressing these feelings early can make a big difference in their emotional well-being.

For more information

Access the Patient Care Standards for Mito

Mito Foundation provides information to help people affected by mito understand clinical trials and how to find opportunities that may be relevant to them.

Clinical trials help researchers test new ways to prevent, diagnose, treat and manage mito. Some trials test whether a treatment is safe and whether it may help people.
Other clinical studies may look at symptoms, diagnosis, genetics, quality of life, or how mito affects people over time.
Clinical trials are carefully planned. The therapies being studied may be at different stages. Trials may not be available for every type of mito, and not every trial will be right for you. Some trials are only open to people with a confirmed genetic diagnosis, specific symptoms, a certain age range, or the ability to attend study appointments.

Mito Foundation’s emerging therapies information explains therapies in development, how clinical trials work, and what you may wish to consider before taking part. You can also use the Therapy Finder to explore therapies in development and see what may be relevant to you.

Learn more about taking part in clinical trials
Use the Therapy Finder

Staying informed

One way to hear about opportunities to take part in clinical trials is to join the Mito Registry.

The Mito Registry helps connect people with research opportunities that may be relevant to them. It also helps Mito Foundation understand how many people in Australia are affected by different types of mito.

This information can help support future research, services and advocacy.

Join the Mito Registry

The Rare Awareness Rare Education (RARE) Portal: MELAS

National Organisation for Rare Disorders: MELAS

Genetic and Rare Diseases Information Centre: MELAS

Cleveland Clinic: MELAS

Mito Support Community – Facebook group

As of June 2025, no active support groups dedicated to MELAS were found in Australia.

MELAS Syndrome and MIDD International Support Group - Facebook group