Questions & Answers

Mitochondria are tiny structures found in almost every cell in our bodies.  They convert the food we eat into the energy we need to survive and grow.

The number of mitochondria in each cell can vary between one and many thousand, depending on how much energy that cell needs.

Busy cells like brain, heart or liver cells need a lot of energy to function properly and therefore have lots of mitochondria.

Many people don't realise that we all actually have 2 different types of DNA in our bodies. Most people are familiar with nuclear DNA which looks like a twisting ladder and makes up 99.9% of the total DNA in our bodies. It's responsible for determining all the unique characteristics that make us who we are.

Slightly less familiar is mitochondrial DNA which is a tiny ring-shaped structure. It plays no part in determining our unique characteristics but is crucial for the production of our energy. 

Our nuclear DNA contains over 20,000 genes whereas our mitochondrial DNA only contains 37 - although it's small, we couldn't live without it!

Mitochondrial disease occurs when our mitochondria are not able to provide the energy our cells need to work properly.

Without the right amount of energy, our cells cannot do their job and they stop performing and start to die.

Yes it is.

Mitochondrial disease occurs when our mitochondria are not able to provide the energy our bodies need.

This is usually the result of a genetic defect which disrupts energy production and is present at birth. This defect can be in either our mitochondrial DNA or in our nuclear DNA.

The true prevalence is very difficult to determine due to the wide range and varying severity of the symptoms experienced. This means it is often overlooked or misdiagnosed. In addition, the range of genetic mutations that can cause the disorder is vast, which makes genetic diagnosis a challenge.

Yes - the vast majority of mitochondrial disorders affect boys and girls equally.

There is a very small sub-group of mitochondrial diseases that may have a more serious onset in boys than girls because of the way they are inherited. These are known as x-linked disorders and include Pyruvate Dehydrogenase Deficiency (PDHD).

It is believed that mitochondrial disease affects all ethnic groups equally although we are not sure that any specific research has been done in this area.

On paper, prevalence may appear higher in the developed world but this is likely to be due to the more advanced healthcare and diagnostic tests available and better record keeping.

Yes, but the disease often has different characteristics depending on the age of onset.

You cannot catch mitochondrial disease, you are born with it. Mitochondrial disorders are caused by genetic mistakes (mutations in our genes).

Lack of energy is a common outward mitochondrial disease symptom but inside the body it's much more serious and complex. Mitochondrial dysfunction may literally cause any symptom in any organ with any degree of severity at any age.

The diagnosis of mitochondrial disease often involves a long and complex journey for both patient and doctor.

Blood tests, spinal fluid tests, muscle biopsies and MRI scans are all useful tools which can indicate when our mitochondria are not working as they should, however 'normal' results from these tests do not always rule out a mitochondrial disorder.

Genetic Testing using next generation sequencing is becoming increasingly popular but is only available to patients through research projects and is not yet available on the NHS. We are proud to fund this testing at a number of UK centres.

We are hearing how important it is for doctors to look closely at the clinical picture - listening to and observing all the patients symptoms (which may initially appear unrelated) and taking a detailed family history can often be the key to putting the pieces of this complex condition together.

Mitochondrial disease is very rare. With symptoms of the disease beginning at any age and affecting any body system in ways that are not clearly linked, you can see why it is particularly challenging to diagnose.

Many symptoms are common to other diseases and these need to be ruled out before the diagnosis of a mitochondrial disorder is arrived at.

In addition there are lots of different genes involved in healthy mitochondrial function, any one of which could go wrong and cause disease, so finding the underlying defect through genetic testing is key, but also time consuming.

Once a doctor suspects mitochondrial disease based on symptoms of the patient, there are a number of tests that must be undertaken to try and confirm this diagnosis which again takes time. You can read about these in the question above.

The severity of the disease ultimately depends on the underlying genetic cause. With maternally inherited mitochondrial disease, a person may have a certain percentage of their mitochondria not working.

If it is a small percentage, their symptoms may be mild or not begin until later in life. If it is a large percentage then symptoms often begin in early childhood and can be severe and often life limiting.

This is not the case with most nuclear DNA mutations, where severity is much more closely linked to the specific genetic mistake (mutation). As a rule, autosomal recessive nuclear DNA mutations with early onset are the most severe. Autosomal dominant disease such as AD POLG / AD Twinkle / AD RRM2B etc. tend to have a later onset.

There are also circumstances where the severity is organ dependent eg. the brain in Leigh Syndrome. The involvement of such a key organ makes this a very severe form of mitochondrial disease with knock-on effects to many other organs. In addition the involvement of the liver in Alpers causes acute liver failure in many patients.

The various numbers refer to the various processes involved in energy production (the electron transport chain) in the mitochondria. A higher number is not worse - it just helps doctors explain which part of the mitochondria might not be working well and helps direct treatment or genetic testing.

Because these mitochondrial components live alongside each other, by having one portion not work properly - another portion may also not work as intended - so a person can have more than one complex affected.

Mitochondrial disease is a progressive condition which means that the prognosis is it will get worse over time.

The rate of progression however varies hugely from patient to patient and is dependent on a number of factors including the underlying genetic defect, the organs affected by disease and exposure to infection/medical or physiological stress.

Some patients have chronic symptoms that remain stable for a number of years and others may have a slow and steady or rapid downhill progression.

There is also a very small group of patients who appear to have a reversible form of mitochondrial disease that begins in infancy and improves with time if sufficient medical support is provided initially. The mechanisms causing these reversible forms of mitochondrial dysfunction have not yet been fully elucidated but mutations in the TRMU gene or the mitochondrial DNA point mutation m.14674T>C seem to be important.

Every patient is different when it comes to mitochondrial disease.

There is no clear evidence that immunisations themselves hurt mitochondria or mitochondrial disease patients.

Medical stress (fever, dehydration, illness, revving up the immune system) may bring out or worsen metabolic disorders. Thus, there have been some patients where the fever after an immunisation led to symptom onset or worsening. In these individuals it was not directly the immunisation that led to issues.

Doctors recommend that patients receive immunisations. If they are sensitive to declining during medical stress, spacing out immunisations and tight fever-control may help (but this type of approach is not based on medical science but rather what physicians call 'anecdotal experience').

This topic is still actively being studied and at present there is no evidence to link mitochondrial dysfunction with increased rate of infection or indeed immunodeficiency.

We know that having mitochondrial disease leads to more chronic non-life-threatening infections (colds, ear-infections) and in some patients having these medical stressors recurring frequently leads to a decrease in quality of life. This is more likely to be because shrugging off these types of infections might be more difficult for the patient with mitochondrial disease, probably as a result of the impact on their other organ systems.

There is one condition, Cartilage Hair Hypoplasia, where a link with mitochondria has been established.

Following are some medications that have been flagged as having contraindications in some patients with mitochondrial disease. However it is unwise to stop any prescribed medications abruptly.

If you are concerned about the medications you are taking, then you should discuss this with your doctor at the earliest opportunity.

Even though mitochondrial disorders are currently incurable, certain interventions may be helpful in reducing the impact of the condition and limiting further disability.

Supplements may be helpful in slowing the progression of the disease and medications or assistive devices may be useful in reducing specific symptoms.

Dietary alterations may improve wellbeing and making lifestyle changes, such as taking moderate exercise, could actually improve mitochondrial health.

A new wave of experimental drugs are currently in development, which aim to prevent or reverse some of the main symptoms of mitochondrial disease.

In general, mitochondrial diseases are progressive diseases and a substantial number of children with mitochondrial disorders do not reach adulthood. 

The rate of progression can be variable and unpredictable but most patients will eventually develop involvement of several organs. When there is cardiac involvement, brain involvement or stroke-like episodes the disease tends to be more severe but every case is different.

Although there are currently no real treatments or a cure, there is now money being invested in research into mitochondrial disorders and many exciting discoveries are being published that we hope will lead to treatments to slow the progression of these diseases for future cases.

Our understanding of mitochondrial biology has improved along with drug design, and a number of compounds are on the horizon.

We are also in a better position to assess the efficacy of potential cures and drugs as a result of developing patient cohorts and because of highly organised and structured clinical trials.

There is hope.

The inheritance of mitochondrial disease is complicated.

Depending on the underlying genetic error, it can be passed down from the mother or father or both. It is also possible that the mistake may have arisen for the first time in the affected person.

I want to know more.

It is important to determine which type of mitochondrial disease inheritance is present (see Q25) in order to predict the risk of recurrence for future children.

If a family has a genetic diagnosis there are options to test future pregnancies (See Q27).

For families without a genetic diagnosis, making the decision to have another child involves a degree of risk. The level of risk involved can be estimated from the pattern of inheritance of the disease in the family.

If you have a genetic diagnosis for your mitochondrial disease, it is possible to test a pregnancy using CVS or amniocentesis to see if the baby might be affected.

There is also the option of using an IVF procedure called Pre-Implantation Genetic Diagnosis (PDG) which can test an embryo to see if it is affected.

If you have already had an affected child then you are potentially at risk of this happening again (see Q26).  

There are a number of reproductive choices available to families facing these challenges and they include adoption, egg or sperm donation, IVF with Pre-implantation Genetic Diagnosis (PGD) and more recently Mitochondrial Donation Techniques.

Yes. Reproductive techniques like egg/sperm donation and PGD are currently able to prevent the transmission of nuclear mitochondrial DNA disease to the child, and also prevent the child passing on the disease to its future generations.

For families with mitochondrial DNA disease, until recently, only egg donation could achieve the same results.

In 2015 a new technique was introduced in the UK called Mitochondrial Donation. This is an IVF technique which uses the mother and father's nuclear DNA combined with healthy mitochondria from a donor woman. This technique will prevent transmission of maternally inherited mitochondrial disease from mother to child and also ensure that child will not carry the disease to its future generations.

For a long time, mitochondrial disease was considered a rare childhood disorder, however in the last decade it has been discovered that many more common disorders may have an underlying mitochondrial basis including Parkinson’s disease and Alzheimer’s disease.

In addition some forms of cancer, Diabetes Mellitus and epilepsy can result from problems with mitochondrial function.

There are a number of different types of research study that families can get involved with, but whether you take part very much depends on what you want to get out of it.

Mitochondrial disease is actually a term used to describe a group of diseases affecting energy production.

Further information on the following can be found by clicking here.

Alpers, Mitochondrial DNA Depletion Syndrome, Leigh Syndrome, Leber's Hereditary Optic Neuropathy (LHON), MELAS, MERRF, MNGIE, Mitochondrial DNA Deletions, NARP, Large Scale Mitochondrial DNA Deletions.

For many patients mitochondrial diseases are inherited conditions that run in families. This can be particularly hard to understand if the disease has arisen in a child from two apparently healthy adults. To learn more click here.