General Advice

Everything that the body does, from staying warm, to moving and thinking, needs energy. The energy that we use comes from the proteins, carbohydrates and fats in our food. We are unable to use these directly, but instead need to convert them in to a form of energy that cells can use called ATP. You can think of this like a battery. This converts chemical energy into a different form (in this case electrical) that is easier to use. For our bodies, the conversion from food energy to ATP happens in mitochondria. If your mitochondria are not working properly then you are less able to convert food into ATP. For cells that require a lot of ATP, for example your muscles, this is a problem and they may become weaker and get tired faster. Click the items below to learn more.

Alcohol

There is no reason why patients should avoid alcohol, but as with all things moderation is advisable. Excess alcohol can damage both the muscles and the nervous system and it important not to add to any damage caused by the Mitochondrial Disease itself.

Diagnosis

Diagnostic Challenges

  • There are many different clinical presentations within Mitochondrial Disease and the condition often mimics other conditions which adds complexity to diagnosis. For example, problems with eye movement are a common symptom of Mitochondrial Disease however many different diseases cause similar symptoms which inevitably leads to a delay in diagnosis, until other causes are ruled out.
  • For some conditions, it remains a real challenge to detect the mitochondrial abnormality. This might be because the biochemical change that we see is very subtle or alternatively because there are many, many hundreds of different genetic faults (mutations) in patients with Mitochondrial Disease. The identification of these mutations can be like searching for a needle in a haystack.
  • It is now believed that about 2,000 proteins (or building blocks) are required to make a mitochondrion work. A defect could theoretically affect any of these building blocks and many of the building blocks themselves have not been properly identified in human subjects. This means that both doctors and scientists still have a lot to learn even about the way mitochondria work. Finding abnormalities of mitochondrial function, defining the pathological (disease causing) mechanism and developing treatments, remains something which is being actively pursued in many large centres around the world.

Diagnostic Strategies

If you or your child is suspected of having Mitochondrial Disease the doctors will undertake a number of investigations. These will determine the nature and also the extent of the Mitochondrial Disease.

Blood and urine samples

Blood samples are very useful to investigate whether or not patients have a high level of lactate (a bi-product of faulty mitochondria). However, lactate levels can vary substantially, particularly if the sample was difficult to obtain, and many patients with Mitochondrial Disease can have normal blood lactate. Some doctors look for other metabolites such as alanine, in blood and occasionally urine. On the whole, whilst these metabolites give important clues as to the presence of Mitochondrial Disease they are by no means specific.

Blood might also be used to detect genetic faults (mutations). In patients where a genetic mutation is well known then blood is a very useful tissue to investigate for some but not all Mitochondrial Disorders. Certainly well described and well known Mitochondrial Diseases such as Leber’s hereditary optic neuropathy and the 8344A>G MERRF mutations can be detected easily in blood and this is the tissue, which most centres would investigate. Nuclear genetic disorders can certainly be detected in blood without difficulty and again a blood sample would remain the tissue of preference to investigate patients with suspected Mitochondrial Disease or family members in patients with Mitochondrial Disease if this was deemed appropriate by both the patients and the doctors.

Urine samples are very helpful for the investigation of the 3243A>G MELAS mutation. The reason for this is that the 3243A>G MELAS mutation might be at quite low levels in blood and therefore difficult to detect, where as in urine it is present at a much higher level.

Lumbar Puncture

The brain and spinal cord sit in a fluid called cerebrospinal fluid. Sampling of this fluid by lumbar puncture can be useful in the diagnosis of Mitochondrial Disease, particularly in children. As this fluid surrounds the brain, its composition gives important clues as to how the brain is functioning. A lumbar puncture involves placing a small needle under local anaesthetic into the small of the back in order to collect a very small volume of this fluid. A lumbar puncture test is usually only done in the investigation of Mitochondrial Disease in children. A lumbar puncture test is helpful in distinguishing Mitochondrial Disease from other diseases and can allow detection of high levels of lactate in the cerebrospinal fluid, which surrounds the brain and spinal cord. Lactate is produced if mitochondria are not working well and in some patients, high lactate levels are seen only in the cerebrospinal fluid and not in the blood. Thus it is a valuable test in children who predominantly have neurological problems.

Muscle Biopsy

For many patients with Mitochondrial Disease, doctors recommend a muscle biopsy. Muscle is in fact a very good tissue to investigate because it is commonly affected in Mitochondrial Disease and several tests can be done on the muscle biopsy that are extremely helpful. It is certainly possible to look at the distribution of mitochondria on a muscle biopsy and actually to measure the activity of certain enzymes crucial to mitochondrial function. In both children and adults, this may be extremely helpful in finding whether or not a mitochondrial defect is present and also understanding the nature of the mitochondrial problem. These muscle biopsies are taken and may be processed fresh, or more often frozen, in specialised centres within specific countries. In children, defining whether or not there is a biochemical defect can be extremely helpful in determining whether Mitochondrial Disease is present. Indeed it may be the only abnormality that we are able to detect.

The muscle biopsy is also very helpful in terms of genetic analysis for Mitochondrial DNA Diseases. Mitochondrial DNA mutations might only be present in high levels in muscle and not in high levels in blood and thus detecting the abnormality is so much easier in a muscle biopsy than in the blood sample. Studies of either deletions (where a bit of mitochondrial DNA is missing) or rare point mutations (where only a single base is changed in the 16,500 base pair genome is abnormal) might only be detected in muscle. Therefore the extensive genetic investigations that are performed are often better done in muscle biopsies rather than in blood samples.

Imaging

In many patients there is disturbance of brain function associated with Mitochondrial Disease. This disturbance of brain function is picked up clinically, but working out which bits of the brain are affected is often helped by taking pictures (or images) of the brain. There are two main modes of imaging, one is using a CT scan, which is like a sophisticated x-ray and the other is using magnetic resonance imaging (MRI scan). On the whole, a MRI scan gives much more information, but is more difficult to perform since it usually takes at least 20 minutes (much longer than in a CT scan) to obtain good quality images of the brain. These images can be extremely helpful in working out whether patients have Mitochondrial Disease and also the severity of the disease.

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The conversion of food energy into ATP is a crucial function of mitochondria. You might think that because affected mitochondria are less efficient at making ATP that you could overcome this by eating more.

Unfortunately, this is not the case and all that this achieves is that you get heavier. Nor does it seem that one type of food is easier to convert into ATP than another, and so high carbohydrate or high fat diets are not of benefit. Food contains vitamins and minerals as well as energy and it has been suggested that increasing the amount of certain vitamins may help. Many patients are prescribed ubiquinone, a vitamin that works in the mitochondria. No one is certain that this is of benefit, but there is no doubt that some patients feel better taking ubiquinone. However, others feel no benefit. In the clinic we usually suggest people try it for a period of 3 months to see if it helps. Some younger patients are also given riboflavine and thiamine vitamins. There is even less evidence that these help, but again they are unlikely to do harm and do help some patients.

During minor illnesses, it is important to avoid fasting and dehydration. Many patients benefit from having small snacks or high calorie drinks at hand to consume during vigorous activity.

Overall, the best advice is to eat as balanced a diet as possible, and that it may be worth trying ubiquinone or other vitamins on the advice of the specialist.

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Driving

It is important to stress that whilst we can offer advice as to your suitability to drive the final decision lies with the DVLA. Furthermore it is up to you the patient to inform the DVLA of any medical conditions that may affect driving. The DVLA will then send you a questionnaire to fill out and may contact your specialist for an opinion. If you continue to drive without informing the DVLA, your insurance would be invalid and could lead to you being prosecuted. The advice given below applies only to a standard car and motorcycle licence; the regulations for LGV and PCV licences are far stricter and you would need to check with the DVLA carefully.

There are several potential complications that mitochondrial patients may develop that can influence driving ability:

Epilepsy

Some patients with MELAS or MERRF may develop seizures. If you have an epileptic seizure you cannot drive for at least six months, but additional seizures or a predisposing factor such as MELAS or MERFF makes this more likely to be one year. It does not matter if the seizure happens during the day or at night. It is your responsibility to inform the DVLA and your insurance company. After the specified time period (six or twelve months), as long as you do not have any further seizures you would be able to reapply for a licence. It does not matter if you are on anti- epileptic medication or not. The only exception to this is in the rare case that patients only ever have seizures at night. If you have had exclusively night-time seizures for three years (with none during the day), you can re-apply for a licence to drive only during the day.

Vision

All drivers must be able to read (with the aid of glasses or contact lenses if worn) a number plate at 20 metres. The standards are stricter for LGV/PCV licence holders. Certain groups of our patients, particularly those with LHON or OPA1, can suffer a significant loss of visual acuity and may need to advise the DVLA of this.

Patients with difficulties in moving the eyes (CPEO) are not prevented from driving unless this leads to significant double vision. Car licence holders can continue to drive as long as the double vision can be corrected with prisms or with an eye patch.

Another common problem for our patients is the development of drooping eyelids (ptosis). There are no specific rules about this, but if vision is obscured by your eyelid then driving may not be safe. In these cases you would need to consult the DVLA for advice.

Deafness

Profound deafness is not a bar to holding a car licence, but holders of LGV/PCV licences must be able to prove that they can communicate in an emergency by speech or with a MINICOM device.

Diabetes

Patients on insulin treatment for diabetes must be able to recognise the onset of a hypoglycaemic event and meet the vision requirements above. Normally only a temporary licence of 1 to 3 years is issued with the need to renew. Patients on tablet or diet controlled diabetes should let the DVLA know but are able to continue driving as long as other requirements are met (eg vision).

Weakness and inco-ordination

The requirements are that any disability is not “likely to affect vehicle control because of impairment of co-ordination and muscle power.” This is obviously difficult to define and you may need to contact the DVLA for advice.

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Drug Information

In general, there is only one drug that you should not take with Mitochondrial Disease and that is the anti-eplieptic drug called sodium valproate. There are however others that should be used with caution.

Patients with Mitochondrial Disease should not take the anti-eplieptic drug called sodium valproate. Sodium valproate can interact with mitochondria and it is best avoided in Mitochondrial Disease where possible.

Metformin, should also be used in caution because rarely it can increase lactic acid production in the body. This can also be increased in mitochondrial disease, and so the two together could in theory lead to high levels. The same is true of an antibiotic called linezolid. Most of these drugs are not absolutely contraindicated (suggested that the drug should not be used), but there are often alternatives that could be used instead. Many other drugs may provide more benefit than risk.

The best advice is to consult with your specialist when you start a new drug. Other drugs that should be used with caution include:

• Aminoglycoside antibiotics(eg Gentamicin) – rarely problematic but must be avoided in patients carrying m.1555A>G mutations.

• Zidovudine– may cause mitochondrial depletion.

• Statins– usually well tolerated but should have blood tests to monitor muscle enzymes.

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Education

Some children with Mitochondrial Disease will attend mainstream school, while others (or their parents) will find the environment of a special school more appealing. In either case, the class teacher and head teacher should be made aware any physical problems (epilepsy, postural abnormalities, feeding or mobility problems) or learning difficulties the child has acquired as a result of Mitochondrial Disease.

This used to be done with Statement of Special Educational needs (SEN). However statements are being replaced by Education, Health and Social Care Plans (EHCP) and almost all children diagnosed with Mitochondrial Disease will have their educational needs assessed in this way. Children with a statement are undergoing a transition and it is anticipated that all children will have moved on to EHCPs by April 2018.

Parents will have input into the process of ECHP's and we may be asked to provide additional information on the patient’s medical condition and its implications for education. More information on the EHCP process can be found at www.gov.uk. In England and Wales it is now unlawful for any school to discriminate against disabled pupils. Parents have means of redress via the Special Educational Needs and Disability Tribunals and through admissions and exclusions panels. For more information view the Disability Rights Commission website where there is a section on education www.drc.org.uk.

Children with Mitochondrial Disease should have easy access to fluids and avoid excessive exercise. However, it is physically and socially important that children participate in school life and encouragement should be given for the child to do as much as they can without over-exerting themselves. Your specialist will be able to give you more details on what you might expect your child to be able to do and with your permission should be able to provide the school with a medical report outlining the child’s abilities.

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Employment

Patients with Mitochondrial Disease have the same employment rights as any other employee although it is likely that their employer will be less familiar with the particular problems encountered in this illness. Clearly individual circumstances differ, but your specialist should be able to advise your employer on your ‘fitness to work’. It may be that in response to illness your employer offers you an alternative job. Again, it may be advisable to discuss the suitability of such employment with your Mitochondrial Disease specialist and also with disability employment advisers (DEAs). You can find out more about DEAs via your local job centre. Alternatively your health may prevent you from doing any suitable job with your employer. In that situation they should be able to advise you with regard to the level of private health insurance or critical illness cover they provide.

Choosing a career is very much up to the individual, but our general advice would be that heavy physical work in hot conditions should be avoided. Many patients with Mitochondrial Disease are likely to experience weakness as their disease progresses and this could severely limit their ability to perform heavy physical jobs. Dehydration and over-exertion can also exacerbate the lactic acidosis present in some patients. Light physical work is however possible for many Mitochondrial Patients. Other considerations include whether the job involves driving (see Driving) or requires physical adaptations to the workplace in order for you to perform it (e.g. MINICOM, seating, keyboard).

Another website that may be able to provide advice or information relevant to your particular employment circumstances is the Disability Rights Commission

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Exercise

Because in Mitochondrial Disease the cells cannot make ATP in sufficient quantity, anything that requires a lot of ATP such as exercising a muscle will mean that the body will not be able to keep up with demand. This has two main effects:

- the muscle will become tired sooner than normal,

- the muscle makes other compounds such as lactic acid in an attempt to keep up with energy demand. This can lead to pain and cramp in the muscles and patients often feel “like they have run a marathon” even after only moderate exercise.

The temptation is to avoid all exercise so that you never get to this stage, but this is not recommended for two reasons:

- it is important for general fitness to exercise and as well as exercising the muscles, it is important to keep the heart and circulation healthy.

- there is good evidence that if you become very unfit this will adversely affect your muscles. In many patients’ muscles there is a mixture of good and bad mitochondria and the hope is that exercise can increase the good mitochondria, boosting the level of ATP back to normal and so avoiding symptoms. At this stage this remains just a theory and there are large trials looking in to this idea.

At the present time our advice is to exercise regularly at a level that feels comfortable, but without pushing yourself to the point that your muscles become painful.

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Holidays

In general there are no activities that patients should avoid, but clearly a sensible approach is needed when choosing a holiday. For patients with severe weakness and fatigue, a hiking trip to the Himalayas is probably not a good idea. Having said that, we always encourage patients to stay as active as possible and are often amazed by what people can achieve.

Although there are no specific problems with flying patients should avoid becoming dehydrated and carefully consider their diabetes management on long-haul flights. Patients with Mitochondrial Disease need the same vaccinations as any other traveler and some of these can produce a mild fever or ‘flu-like' symptoms, which may be important to consider in children with Leigh disease. In this situation, it would be best to ask your specialist regarding vaccination. Similarly, some drugs used to prevent malaria may have undesirable side-effects particularly in children with epilepsy. Again, it would be best to discuss this with your specialist in clinic.

One sensible precaution in case you do become ill whilst abroad, is to carry a simple summary sheet with your diagnosis, which medications you take and contact details for your GP and specialist on it. We can provide you with this information in the clinic.

Patients also need to inform their travel insurance company of their diagnosis. Normally this will have no effect on the premium or the cover offered, but in some cases the company will contact your specialist for more information about the condition.

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Operations

There is no specific risk in having a general anaesthetic. However, it is important that the anaesthetist knows that you have Mitochondrial Disease as sometimes patients require additional assessments of breathing, swallowing or cardiac function. The anaesthetist can then make a better judgement of any potential risk and advise you accordingly and full care guidelines for professionals can be found here.

We also recommend that you notify your specialist as soon as possible before any planned operation so that any potential risks can be identified. In some cases it may be possible to understand more about your Mitochondrial Disease by looking at any tissue removed at operation. To do this your specialist would need to obtain your consent and speak to your surgeon well before the surgery.

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Mind and Behaviour

Patients with Mitochondrial Disease can experience 'psychological' or 'cognitive' difficulties. Common psychological difficulties include low mood or anxiety. These changes may be first noticed by partners or other family members, for example a person becomes more withdrawn, irritable, seems preoccupied or there is a change in personality. This link gives more information about these types of difficulties http://www.nhs.uk/Conditions/stress-anxiety-depression/Pages/low-mood-stress-anxiety.aspx.

'Cognitive functions' refer to processes such as memory, learning, information processing and attention or concentration. Patients with Mitochondrial Disease can experience difficulties in some of these areas. It may be useful to have a neuropsychology assessment particularly if these types of difficulties are impacting on work or education.

It's worth remembering that we can all experience psychological or cognitive difficulties in our lives and that these can arise from many different causes not just Mitochondrial Disease.

If you, or someone you know with Mitochondrial Disease, are/is experiencing any of the above difficulties then it may be helpful to discuss this with your GP or neurologist.

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Monitoring

Mitochondria are found in every tissue in the body and any of these can potentially be affected in Mitochondrial Disease. By no means will all patients develop complications of their disease and the fact that we sometimes ask for tests does not mean that we think that you have a particular problem. Nevertheless, we feel it is prudent to look for complications that we know can happen, because a lot of them can be effectively treated if caught early enough.

Blood tests

We tend to perform a routine screen of blood tests every time you come to clinic. These are for a wide variety of problems, for example a low blood count, liver or kidney problems. One particular thing that we look carefully for is the development of diabetes as this is a common problem in our patients. We can sometimes detect this on a blood test before any symptoms are apparent, and as with most things it is easier to treat if caught early.

Heart tests

We know that the heart can be involved in Mitochondrial Disease, particularly in the MELAS mutation. We can pick up changes in the heart using simple tests before they cause symptoms. The main one that we use is an electrocardiogram (ECG). This involves placing sticky electrodes on the chest wall and recording the electrical activity of the heart. The procedure is painless and usually takes only a few minutes. In patients with MELAS we would want to do this once a year, however in other mutations we feel that every other year may be enough.

In patients with abnormalities on the ECG, or with other symptoms such as chest pain, we would normally also perform an echocardiogram (“ECHO”). This involves putting cold jelly on the chest and using an ultrasound probe to take pictures of the heart. As with an ECG it is painless, but it usually takes longer (about half an hour).

The point of both these tests is that we can often pick up treatable problems before they cause symptoms.

Neurophysiology

EEG : You might be asked to attend for an electroencephalogram (EEG). This measures your brain’s electrical activity. To do this we stick twenty small electrodes on to your scalp. This is painless and the adhesive gel washes out completely. All you then have to do is to sit in a comfortable chair and relax. We might ask you to overbreathe for a couple of minutes which can make you feel a bit light headed and we might also flash a strobe light in the room. Both of these make the test more accurate but have no long-term effects. The reason that we record the EEG is that it gives us information on how the brain is working. For example, some patients have seizures and the EEG can tell us which parts of the brain are involved. Similarly it can give us information on how well the brain is able to use food energy to make ATP.

Nerve conduction studies: Some patients complain of tingling in their hands and feet. If this is the case we may ask you to have Nerve conduction studies, which can tell us if the nerves supplying these areas are healthy. To do these we give small electric shocks to the nerves and measure the response. We might also put a small needle in different muscles to measure the activity. This all sounds a bit brutal, and it does hurt a bit. However, the doctors doing the tests are experts at making things as painless as possible and we can gain valuable information from them. For example, tingling hands can be caused by a trapped nerve in the wrist and a small operation can cure this completely. Unfortunately, if the nerves are damaged as part of the mitochondrial disease it is not possible to reverse this, but nevertheless there are effective treatments we can use to reduce the symptoms.

Respiratory function

The muscles that move the chest wall and allow us to breathe can be affected in mitochondrial disease. This can cause breathlessness, but sometimes the only symptoms can be headaches in the morning or excessive sleepiness. One of the best ways to check for respiratory muscle weakness is with a simple breathing test that we can do in the clinic. We will ask you to blow as hard and as long as you can into a tube and from this we can measure your lung capacity and strength. The test is quick and has no long term effects. Sometimes we need more accurate information and you might be asked to attend the respiratory function laboratory for more detailed tests. Similarly, if we suspect that your breathing is affected during sleep, we might admit you overnight on to the ward so that we can put a small sensor on to your finger tip and measure the oxygen level in your blood over the whole night.

Eye tests

The eyes can be affected in several ways in mitochondrial diseases and we regularly perform eye tests in the clinic. Firstly the muscles around the eyes can be involved; this causes drooping of the eyelids (ptosis) and a reduced ability to move the eyes around (ophthalmoplegia). Secondly, the eyes themselves can be affected leading to blurred vision. It is often possible to improve patients’ vision with for example special glasses or minor surgery to lift the eyelids.

Hearing

Many patients develop hearing problems as part of their illness. Usually this can be helped with hearing aids. We often ask patients to attend the audiology department for detailed hearing tests and to be fitted with suitable hearing aids.

Swallowing

Mitochondrial disease can affect the muscles of the tongue and throat leading to problems with speech and swallowing. We often ask our dieticians and speech and language therapists for their advice on measures that can be used to improve matters. Sometimes this can be achieved with a change in diet or the use of dietary supplements. When swallowing becomes more problematic we may request a test of swallowing called a videofluoroscopy which provides a moving image of the swallowing process. Some patients develop such severe problems that they are no longer able to swallow safely without food going the wrong way into the lungs and in these patients we often ask the surgeons to pass a fine tube directly through the abdominal wall into the stomach. This is called a PEG tube and allows liquid food to be dripped slowly into the stomach over several hours. Where assessed safe to do so patients may still eat small amounts of food by mouth, but this alone would be insufficient to meet the body’s nutrient and energy demands. PEG feeding may also be used to supplement an inadequate diet due to severe loss of appetite or where calorie intake is insufficient to sustain appropriate growth.

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