Mitochondrial disease

Mitochondrial disease is a group of conditions that can affect multiple parts of the body, including the heart, brain, liver, and nervous system. These conditions are caused by genetic changes in the mitochondria, which produce energy needed to power cells. The symptoms and severity of mitochondrial disease varies greatly among those affected.

Mitochondrial myopathies are a subgroup of mitochondrial disease that primarily affect muscle function and lead to muscle weakness, muscle fatigue, and exercise intolerance.

There are several types of mitochondrial disease, including:

• Kearns-Sayre syndrome (KSS)
• Chronic progressive external ophthalmoplegia (CPEO)
• Leigh syndrome (MILS, or maternally inherited Leigh syndrome)
• Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
• Mitochondrial DNA depletion syndromes (MDDS)
• Myoclonic epilepsy with ragged red fibres (MERRF)
• Leber hereditary optic neuropathy (LHON)

Mitochondrial disease can affect multiple systems in the body. When symptoms start, how severe they are, and the combination of symptoms varies from person to person and depends on the specific gene causing the condition and how much mitochondrial DNA is affected.

Some types, such as Leigh syndrome, begin very early in life. These can get worse very quickly and be life-shortening. Although, in recent years, survival has improved greatly due to better information and targeted supportive care.

Mitochondrial disease that begins in adulthood usually progresses more slowly. For some people, it can lead to difficulty with everyday activities in later life, but their life expectancy may be the same as that of the general population. Support from specialists can greatly improve the impact of brain involvement, heart problems, major gut problems, and breathing difficulties, which would otherwise shorten life expectancy if not treated.

Some common symptoms include:

Muscle weakness

Progressive weakness in the arms, legs, and face is a common symptom. Facial weakness can cause droopy eyelids (ptosis) and difficulty moving the eyes (ophthalmoplegia). People often experience exercise intolerance, where muscle weakness worsens during or after physical activity and pain develops. This may also cause nausea, headaches, and heart palpitations. It’s important to seek medical attention if these symptoms happen.

In severe types of mitochondrial disease, muscle weakness may be obvious, particularly in small babies who may seem very ‘floppy’ (hypotonia) and have trouble breathing and feeding.

Neurodevelopment

Some severe types of mitochondrial disease can affect the brain. This can lead to developmental delays, loss of skills (regression), epilepsy, stroke-like episodes, and progressive loss of memory. Not all types of mitochondrial disease with brain involvement get worse – but some can.

The retina (light-sensitive membrane at the back of the eye) may also be affected, and hearing difficulties are not uncommon.

Heart

Heart problems are common. These include arrythmias (irregular heartbeat), cardiomyopathy (heart muscle disease), and heart failure. Regular heart monitoring is crucial to find these problems early and treat them. Some people may develop a very slow heart rate, which could require a pacemaker – a pacemaker is a small device that helps the heart to beat regularly.

Gastrointestinal

Problems with digestion are common in mitochondrial disease and can often be overlooked. Symptoms can include nausea, vomiting, abdominal pain, constipation, and diarrhoea. These happen when the muscles in the digestive tract don’t function properly (gastrointestinal dysmotility). Those affected may also have difficulty swallowing and may experience bloating. These problems can lead to poor appetite and challenges in gaining weight. Support from dietetics services will be required to help manage nutritional needs and can be accessed through a referral from a doctor or specialist.

Endocrine

The endocrine system is a network of glands that produce hormones, which control growth, puberty, and how the body responds to stress. Some types of mitochondrial disease can increase the risk of diabetes. Other endocrine symptoms that may occur are a short stature and thyroid problems leading to hypothyroidism (an underactive thyroid).

Genetic changes

Mitochondrial disease can be caused by genetic changes in either nuclear DNA or mitochondrial DNA. While most of our DNA is contained within chromosomes in the nucleus of our cells, a very small amount is found within the mitochondria. Mitochondria are small structures inside our cells that make the energy the body needs. When a person has mitochondrial disease, their mitochondria don’t make enough energy. This causes symptoms associated with mitochondrial disease.

Inheritance

The inheritance of mitochondrial disease is complex and varies depending on whether the genetic change is in the nuclear DNA or mitochondrial DNA.

Mitochondrial disease caused by a change in mitochondrial DNA is maternally inherited, meaning the change is passed from mother to both sons and daughters, but only daughters can pass it on to their children. Although all children may inherit the genetic change, they can be affected differently. The severity of symptoms can depend on the level of heteroplasmy – the proportion of faulty to healthy mitochondrial DNA. A higher level of heteroplasmy, also known as mutation load, increases the likelihood and severity of symptoms.

Mitochondrial disease caused by a change in the nuclear DNA can follow different inheritance patterns: autosomal dominant, autosomal recessive, or X-linked recessive. In rare cases, mitochondrial disease can occur spontaneously from a new change that isn’t inherited. In these cases, there’s no family history of the condition.

For more information, see our inheritance and genetics page.

A doctor will use a range of tests to come to a diagnosis. As mitochondrial disease affects many systems in the body, problems with the liver, kidney or heart may be noticed before muscle weakness. For example, an electrocardiogram (ECG) can detect cardiomyopathy, and a blood test can detect kidney issues and diabetes.

The doctor may do a physical examination to test strength and endurance, and a neurology examination can test the reflexes, vision, speech, and cognitive skills.

Mitochondrial disease could be diagnosed using a blood or urine sample if the genetic change matches an already recognised change.

In some cases, a muscle biopsy may be needed. This involves taking a small sample of muscle and examining it under a microscope. Special stains are applied to the muscle cells to assess their uptake compared to normal muscle cells. In people with mitochondrial disease, mitochondria may gather around the edges of muscle cells – these are called ragged-red fibres.

For more information, see our diagnosis page.

A multi-disciplinary approach, with different healthcare professionals working together, is important in not only managing the condition and symptoms of mitochondrial disease but in also improving wellbeing. This will vary greatly depending on the type and severity. The most severe types will need immediate care and treatment.

Access to a healthcare team

People with mitochondrial disease should have access to a multi-disciplinary healthcare team. It’s important that a person’s GP is informed of their condition, as they are often the first point of contact when unwell and can make referrals to support services as needed. Care may also be managed by a local hospital team and can be referred to a specialist mitochondrial service. Management and treatment must be tailored to the specific needs of the person.

Monitoring

Mitochondrial disease can affect multiple systems in the body, and it’s important to regularly monitor for potential complications so treatment can be started quickly. This can include gastrointestinal investigations, blood tests, heart tests such as an ECG and ECHO, nerve conduction studies, breathing tests, and eye tests.

Although there is no cure for mitochondrial disease, many of the problems associated with some types can be managed well. For example, diabetes can be treated with tablets or insulin, epilepsy with anti-epilepsy medications, hearing loss with hearing aids (or cochlear implants in some cases), and heart rhythm issues with pacemakers. The specialist team can decide what treatment is best.

Exercise and physiotherapy

Staying as active as possible is important. People with mitochondrial disease are advised to exercise regularly at a level that feels comfortable and does not cause muscle pain or feeling unwell. A physiotherapist is a healthcare professional who helps manage symptoms through movement, exercise, and manual therapy. They can come up with a suitable exercise plan to maintain strength and mobility. Regular stretching can help keep joints and muscle flexible and prevent tightness. Strengthening exercises can help to prevent muscle weakening, and aerobic exercise such as walking, swimming, and pedalling can help to keep the heart and lungs as healthy as possible. To find out more about advice for adults, see exercising with a muscle wasting condition.

Nutrition

Fasting and dehydration will put extra strain on mitochondria. It’s important to eat regularly throughout the day and avoid fasting. Daily fluid intake should be increased in warm weather and during exercise or physical exertion. A healthy, balanced diet is recommended to improve overall wellbeing.

Some medications can be harmful to people with mitochondrial disease and should be avoided or used with caution. It’s important to tell a doctor about the diagnosis when being prescribed new medication. Here is a list of medications considered to be dangerous for people with mitochondrial disease. This has been put together by International Mito Patients.

Anaesthesia stops a person feeling pain during a procedure or surgery. If having surgery, the anaesthetist and surgical team should be made aware of a mitochondrial disease diagnosis. They should carry out a pre-operative assessment to assess potential risks and extended post-operative monitoring may be necessary.