The information was provided by The Lily Foundation, a charity dedicated to funding research, raising awareness and supporting families affected by Mitochondrial Disease. The aim of this section is to help improve the understanding of Mitochondrial Disease. The information is for purely educational purposes. It does not constitute medical advice. Every patient with Mitochondrial Disease is different and if you have any concerns about you or your child's health, you should seek direct medical advice from a specialist medical practitioner.
Mitochondria are tiny structures found in almost every cell in our body. 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.
Actually the number of mitochondria in an individual cell is continually changing because they fuse with each other and divide on a regular basis.
There is also variation from cell to cell in the same tissue and between different individuals.Back to top
Many people don't realise that we all have 2 different types of DNA in our body. Most people are familiar with nuclear DNA, which looks like a twisting ladder and makes up 99.9% of the total DNA in our body. It is 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 it 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 is small, we couldn't live without it!
Nuclear DNA is found within the nucleus of our cells. It is linear in shape and it makes up 99.9% of the total DNA in our body.
Within the cell, the nuclear DNA is packaged up into structures called chromosomes. Humans have 46 chromosomes per cell which are arranged in pairs (23 of these come from your mother and 23 from your father). These chromosomes contain between 20,000-25,000 genes.
Nuclear DNA (and the genes that it holds) are responsible for providing the basis for how human bodies are built and work, as well as determining all our characteristics.
This is a special circular type of DNA that is only found within the mitochondria themselves and it makes up only 0.1% of the total DNA in our body
Mitochondrial DNA contains only 37 genes, all of which are essential for normal mitochondrial function (13 of these genes provide instructions for making enzymes involved energy production and the remaining genes help put all the proteins together.)
Mitochondrial DNA is inherited only from your mother (as the father's mitochondrial DNA is destroyed during fertilization). Human cells contain between 100-1000's copies of mitochondrial DNA.Back to top
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.
If a lot of mitochondria in the body are affected, especially in important body organs, Mitochondrial Disease can be very serious and often fatal.
Each affected individual will have different symptoms and severity of the condition. This is sometimes because a different combination of their mitochondria are working and not working within each cell, and each person might also have different cells in the body affected.
Mitochondrial Disease is not a single disease but more like a collection of conditions. The underlying genetic cause may be different for different people but all will result in mitochondria that are unable to produce the right amount of energy, which causes this disease.
Some types of Mitochondrial Disease affect only one organ and some affect multiple organs.
There are times when particular organs or body systems are affected in a recognisable pattern and these have been given 'syndrome names' like for example Alper’s disease, Leigh’s disease, MELAS or MERRF to name only a few. More about these recognised patterns can be found by clicking here (link)
Mitochondrial Disease might also be classified by the specific complex of the respiratory chain that they affect eg Complex I.
Also Mitochondrial Disease may be classified by the specific genetic fault (mutation) that has caused it.Back to top
Yes it is.
A metabolic disorder simply means that one of the processes by which your body makes, uses or disposes of certain materials is abnormal.
Mitochondria perform many metabolic tasks but ‘Mitochondrial Disease’ refers specifically to problems with the task of converting energy from one form into another using the specialized machinery within the mitochondria.
There are also many metabolic disorders that do not affect this process of energy conversion even though they might be occurring within the mitochondria. (an example would be a Urea Cycle Disorder – the process occurs inside the mitochondria, but these disorders are not considered Mitochondrial Disease but are metabolic disorders.)Back to top
Mitochondrial Disease occurs when our mitochondria are not able to provide the energy our bodies need.
This is usually the result of a genetic fault (mutation) which disrupts energy production and is present at birth. This fault can either be in 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. 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.
It is believed that 1 in 200 babies in the UK are born with genetic changes that can cause Mitochondrial Disease, although there are no official statistics that record the number of children that go on from this to develop serious disease.
The incidence of Mitochondrial Disease in the adult population is estimated at around 1 in 4,300 (Gorman et al. Annals of Neurology 2015) and as we learn more about Mitochondrial Disease, and as diagnostic tools improve, we are likely to see a significant increase in diagnosed cases.Back to top
Yes - the vast majority of Mitochondrial Diseases 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.
Childhood disease is usually more severe due to the nature of the genetic faults (mutations) that have been inherited, and is often life limiting.
With adult disease, symptoms may accumulate over time and may be masked by other more common diseases of ageing.
In terms of population prevalence, adult onset disease is actually much more common than childhood disease. This is partly because childhood onset disease is often fatal at a very early age, whereas adults often survive for many years after the diagnosis is made.Back to top
You cannot catch Mitochondrial Disease, you are born with it. Mitochondrial Disease is caused by genetic mistakes (mutations) in our genes.
Mitochondrial Disease can be inherited, but the way this can happen is extremely complicated. It can be inherited from the mother or father or both. It is also possible that the genetic mistake may have arisen for the first time in the affected person.
Lack of energy is a common outward symptom of Mitochondrial Disease but inside the body it's much more serious and complex. Mitochondrial Disease may literally cause any symptom, in any organ, with any degree of severity, at any age.
Children typically present with failure to thrive, motor regression, encephalopathy, seizures, swallowing problems and breathing difficulties like apnoea (long pauses in breathing pattern).
In contrast, adults frequently develop hearing loss, muscle weakness, diabetes, gastrointestinal dysmotilty and fatigue.
Symptoms of Mitochondrial Disease vary hugely depending on the underlying genetic mutation that has caused it.
Patients with similar symptoms are often grouped into categories known as 'mitochondrial syndromes'. These include Alper's Disease, Mitochondrial DNA Depletion Syndrome, Leigh Syndrome, LHON, MELAS, MERF, MNGIE and NARP.
Within a 'syndrome' patients may have different underlying genetic mistake (mutation), but their disease presents in a similar way.Back to top
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 mitochondrial disease.
Genetic testing can provide a definitive diagnosis of mitochondrial disease in many patients. Although the number of patients with a genetic diagnosis is increasing as a result of developments in genetic testing and knowledge from research, a significant number of patients remain without a genetic diagnosis. The Lily Foundation fund this testing at a number of UK centres.
It is important for doctors with specialist expertise to look closely at the clinical picture, listening to and observing all the patient's symptoms (which may initially appear unrelated), and taking a detailed family history, as this 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 Mitochondrial Disease is made.
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 genetic fault (mutation) 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 that are not working.
If it is a small %, their symptoms may be mild or not begin until later in life. If it is a large % 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 (AD) disease such as AD POLG / AD Twinkle / AD RRM2B etc tend to have a later onset.
Although patients with the same nuclear DNA mutation tend to follow a similar pattern of disease progression this is not always the case, and prognosis should be discussed with your specialist doctor on a case by case basis.
There are also circumstances where the severity is organ dependent eg the brain in Leigh disease. 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 Alper's disease, causes acute liver failure in many patients.
The various numbers refer to the different 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 help direct treatment or genetic testing.
Because these mitochondrial components work alongside each other, having one portion that doesn't work properly means that another portion may also not work as intended. This means a person can have more than one complex affected.
Mitochondrial Disease is a progressive condition which means that 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 mistake (mutation), the organs affected by the 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, 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 Disease 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.
There is no clear evidence that immunisations (vaccines) themselves hurt mitochondria or Mitochondrial Disease patients.
Medical stress (fever, dehydration, illness, increasing the work of the immune-system) may bring-out or worsen mitochondrial diseases. Vaccines may cause side effects in some people, including fever, but usually they are mild. However, the diseases from which they are protected with the vaccination are usually much more severe than the side effects caused by vaccination itself. Consequently, the natural infection would cause a serious deterioration of the mitochondrial disease.
Doctors recommend that patients receive immunisations. If they are sensitive to declining during medical stress, spacing out immunisations and tight fever-control may help.
This topic is still actively being studied and at present there is no evidence to link Mitochondrial Disease 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 insults recur frequently leads to a decrease in quality of life. This is more likely to be because 'shrugging off' these type 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 rare condition causing immunodeficiency known as Cartilage Hair Hypoplasia where a link with mitochondria has been established.
Following are some medications that have been flagged as having adverse affects 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.
Medications to be avoided if possible:
Sodium Valproate – commonly used for seizures.
Metformin – used to treat diabetes
Linezolid – an antibiotic used to treat infections
Zidovudine – used for treatment of HIV
Medications that should be used with caution:
Gentamicin – this antibiotic can cause deafness in patients with a specific susceptibility. It is safe in most forms of Mitochondrial Disease.
Tetracyclines, ciprofloxacin and chloramphenicol – theoretical interactions should not prevent use of these antibiotics if they are needed.
Aspirin – should be avoided in children under 12 years of age.Back to top
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, which tend to be more severe when symptoms develop in childhood compared to when symptoms develop in adulthood. There is huge variation in severity across different forms of this condition, and as such, it is recommended that people discuss any queries with their pediatrician or neurologist.
A substantial number of children with Mitochondrial Disease do not reach adulthood, whilst with some forms of adult-onset Mitochondrial Disease, symptoms may only develop later in life.
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 stoke like episodes the disease tends to be more severe but every case is different.
Although there are currently no real treatments or a cure at present, 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 mistake (mutation), it can be passed down from the mother or father or both. It is also possible that the mutation may have arisen for the first time in the affected person.
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 Preimplantation Genetic Diagnosis (PGD) which can test embryos to see if they are affected.
If you have already had an affected child, 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 Preimplantation Genetic Diagnosis (PGD) and more recently Mitochondrial Donation.
Yes. Reproductive techniques like egg/sperm donation and PGD are currently able to prevent genetic mistakes (mutations) in the nuclear DNA that caise Mitochondrial Disease being passed to the child, and also prevent the child passing on the disease to future generations.
For families with mitochondrial DNA disease, caused by mutations in the mitochondrial DNA, 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 fathers nuclear DNA combined with healthy mitochondria from a donor woman. This technique will prevent transmission of Mitochondrial DNA Disease from mother to child and also ensure that child will not pass the disease to future generations.
Mitochondrial diseases are caused by a primary genetic defect in the mitochondria. However, our knowledge of mitochondrial function has expanded over recent years and it is becoming clear that mitochondria have a central role in many other common diseases, such as Parkinson’s disease and Alzheimers disease. In these cases, there is a secondary dysfunction of the mitochondria that contributes to the disease. It is important however to distinguish between primary mitochondrial disease and secondary mitochondrial dysfunction.
Primary mitochondrial diseases are caused by a fault in a gene directly involved in the production of energy (through the respiratory chain), secondary changes in mitochondrial function are caused by factors outside of the respiratory chain.
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.
Some studies involve using existing clinical data from routine follow ups and others require patient participation.
Some trials anonymise data (so you will not get direct personal feedback) and others will provide feedback to participants - either way, your involvement will add huge value to the understanding of this area of medicine. Some studies may not use medical data at all but instead may examine the social impact of this condition.
What exactly will be required from you and what will be reported back, will depend on the exact nature of the study you sign up to, so it is important to talk to your trial coordinator or clinician and understand what is involved.
For more information on the kind of projects you can get involved with please see the Involvement and Engagement section of this website.Back to top
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.
Alper's Disease, Mitochondrial DNA Depletion Syndrome, Leigh Syndrome, Leber's Hereditary Optic Neuropathy (LHON), MELAS, MERRF, MNGIE, Mitochondrial DNA Depletion Syndrome, NARP, Large Scale Mitochondrial DNA Deletions.