MELAS syndrome: symptoms, diagnosis and care in the UK

Mitochondria are the structures inside cells that turn food into usable energy. The Lily Foundation, a UK mitochondrial disease charity, explains that the m.3243A>G change affects how mitochondria convert food into usable energy, so it can lead to a range of symptoms affecting the muscles, brain, ears, pancreas and other organs. MELAS is one of the recognised presentations of that change.

The name is an acronym. It stands for mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes: a disorder of brain and muscle function, a build-up of lactic acid in the blood, and episodes that resemble a stroke. The NHS Rare Mitochondrial Disorders Service describes MELAS as a collection of symptoms that sits at the severe end of a spectrum, with some carriers of the same mutation having no symptoms at all.

That spectrum is the most important thing to understand. The mutation itself is not the same as the syndrome. The Lily Foundation says that fewer than 10% of people with this variant experience stroke-like episodes, while many more develop diabetes, hearing loss or milder muscle symptoms, a pattern called MIDD (maternally inherited diabetes and deafness).

The Lily Foundation lists the features that MELAS can cause. Because the picture differs from person to person, nobody will have all of them.

• Stroke-like episodes: sudden changes in movement, speech or vision not caused by a typical stroke, often with confusion, altered awareness or sometimes hallucinations.

• Seizures or epilepsy.

• Severe or recurrent headaches.

• Memory or concentration problems.

• Severe gut problems.

• Muscle weakness, exercise intolerance, and muscle pain or cramps.

The Lily Foundation explains that 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 look different on brain scans, which is one way specialists tell them apart.

The NHS Rare Mitochondrial Disorders Service describes the episodes as a form of encephalopathy, a disturbance of brain function that can take the form of stroke-like episodes and/or seizures, and notes this is a much more troublesome and difficult group of symptoms to control with a significant effect on lifestyle.

Because the symptoms resemble a stroke, new sudden weakness, speech difficulty or loss of vision should always be treated as an emergency in the first instance. Call 999 rather than waiting to see whether it passes.

The NHS service says diabetes is a very common feature in people with the m.3243A>G mutation, and that it is advisable to see a diabetologist if it develops. Other common problems include poor bowel function, leading to irritable bowel symptoms or severe constipation, and heart problems such as a slightly enlarged heart or one that does not function properly (cardiomyopathy) or changes in heart rhythm, which should be monitored regularly.

The Lily Foundation adds that MIDD features include progressive, usually bilateral, sensorineural hearing loss, and that other possible symptoms are migraines or recurrent headaches, balance difficulties, visual problems and chronic progressive external ophthalmoplegia (CPEO). It stresses that some individuals remain only mildly affected.

According to the Lily Foundation, diagnosis may involve genetic testing of blood, urine or muscle, brain imaging particularly if there are neurological symptoms, blood and urine tests including lactate levels, hearing and eye assessments, and in selected cases a muscle biopsy.

In the UK, diagnosis and ongoing care are led by the NHS Highly Specialised Services for Mitochondrial Disorders, which offer access to expert multidisciplinary teams. The NHS Rare Mitochondrial Disorders Service itself refers to three highly specialised mitochondrial disease centres in Newcastle, London and Oxford. A GP or neurologist can refer you.

Family members may also be affected. The NHS service notes that carriers of m.3243A>G should have regular checks for diabetes, which can be arranged through a GP, and that some people only learn they carry the mutation because a relative has more serious disease.

There is no cure. The Lily Foundation lists the components of care: 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; and nutritional guidance. During stroke-like episodes hospital treatment may be required to manage symptoms and prevent further complications.

The NHS service says there is no really well defined way to treat stroke-like episodes at present. It describes trials of L-arginine in Japan but says it is still uncertain whether it is beneficial. In its own centres it tries to ensure adequate fluids, prompt treatment of infections and aggressive treatment of seizures, and it says an EEG and brain MRI should be performed if possible. It also says sodium valproate (valproic acid) should be avoided in seizure treatment.

The service also advises carrying information about the mutation, in case you need to consult out-of-hours medical services unfamiliar with the disorder. Heart problems may be helped by early intervention with medicines that lower blood pressure or reduce the load on the heart.

In some patients the mutation seems to be a sporadic event with no family history, but in most it is passed down from mother to child. Mothers who carry it contain a mixture of good and bad mitochondrial DNA, and it is currently very hard to predict the level that will be present in a child because of a process called the mitochondrial bottleneck during development of the eggs.

The NHS service urges mothers who are concerned about transmitting mitochondrial DNA mutations to seek specialist genetic counselling. Your GP can refer you to a clinical genetics service.

Call 999 if someone has sudden weakness of the face, arm or leg, slurred speech, sudden loss of vision, a first seizure, a seizure that does not stop, or a sudden change in awareness. Do not wait to see whether it passes.

If you already have a diagnosis, speak to your specialist team early when symptoms change, when you have an infection, or when seizure control worsens. Persistent headaches, new diabetes symptoms such as excessive thirst, or worsening hearing should be raised with your GP.