The mitochondrial disorders are an uncommon group of conditions. They are part of a larger group of conditions called, ‘metabolic disorders’.
There are many different types of mitochondrial disorders. The mitochondria are known as the ‘powerhouse of the cell’. All our organs (our brain, nerves, muscles, heart, liver, eyes and so on) are made up of millions of cells. These cells can only work properly if the mitochondria in the cells work properly. The mitochondria are as important to the cells as the engine is to a car.
The organs with the most mitochondria in them are the brain, nerves, muscles and liver. Because of this, neurological disorders, including epilepsy, occur quite commonly in mitochondrial disorders. Most of the epilepsy caused by a mitochondrial disorder starts in childhood and usually in the first 2 years of life. However, seizures can start within a few days of birth, or as late as the teenage years or, rarely, in adult life.
The seizures can appear in different forms. The most common types of seizures are myoclonic, tonic-clonic, atonic (sometimes called ‘drop seizures’), atypical absences, and focal seizures. However, any type of seizure may happen in mitochondrial disorders.
When a focal seizure happens, it may do so without stopping and can last for many hours or days. This is called ‘epilepsia partialis continua’ (literally meaning ‘continuous partial epilepsy’). This type of seizure is seen in the mitochondrial disorders called ‘Alpers’ disease’ (after the German doctor who first described it), and Leigh’s disease (after the British doctor who first described it).
A diagnosis of a mitochondrial disorder is considered in children where:
- Their epilepsy begins in the first few weeks, months or years of life
- Their epilepsy is not caused by any obvious infection, such as meningitis or encephalitis, or brain malformation
- Their epilepsy does not respond to epilepsy medicines
- They have delayed development
- They have symptoms of other organs not working normally; this includes liver disease, poor weight gain, a small head or short stature
If the paediatrician thinks that the child might have a mitochondrial disorder, they will organise an EEG, MRI and other investigations. The EEG is not always helpful but it may show a pattern that is seen in one or two mitochondrial disorders. Two of these are Alpers’ disease and Leigh’s disease. The EEG patterns in both - but particularly Alpers’ disease - often shows a pattern called ‘periodic lateralising discharges or ‘PLEDS’ for short. The EEG may also show a pattern called ‘burst-suppression’. An MRI brain scan may show abnormalities within the part of the brain called the ‘basal ganglia’. It may occasionally show ‘cerebral dysgenesis’ (which means abnormalities in how the brain was made). Over time, the MRI scan will usually show shrinkage of the brain (‘atrophy’). Blood tests and a lumbar puncture test usually show high levels of lactate – which is one of the metabolic ‘waste products’ of the cell. Genetic-testing (on DNA) might also be able to make a diagnosis of a particular type of mitochondrial disorder. However, a definite diagnosis may only be made by examining a piece of muscle through a ‘muscle biopsy’.
Treatment is nearly always necessary to stop or prevent the seizures in the mitochondrial disorders. However, the seizures may be very difficult to control. The most commonly used epilepsy medicines include the benzodiazepines (clonazepam and clobazam), levetiracetam, lamotrigine, piracetam, and vigabatrin. Sodium valproate can also be used, but preferably not in young children (less than 2 years of age) or if the child has any liver disease. This is because it might make the child seriously unwell. The ketogenic diet may sometimes be helpful in a few children, but this will again depend on the particular type of mitochondrial disorder. Epilepsy surgery or the vagal nerve stimulator (VNS) is rarely able to help treat seizures in the mitochondrial disorders.
Information about treatments for children can be found on the Medicines for Children website.
There may be research studies taking place that are relevant to this epilepsy syndrome. Your child’s hospital doctor will be able to discuss this with you.
If your child has a mitochondrial disorder, it is likely they will have prolonged or repeated seizures. Your child’s hospital doctor will discuss a ‘rescue’ or emergency care plan with you to treat any prolonged or repeated seizures.
Most mitochondrial disorders are progressive. This means that the symptoms and the seizures will worsen over time. This worsening may happen over weeks, months or many years. How quickly the progression happens will depend on the particular type of mitochondrial disorder. The seizures in most mitochondrial disorders are usually very difficult to control. Unfortunately, for most mitochondrial disorders there is no specific treatment, such as diet or surgery, which can stop the seizures or stop the disorder from progressing.
What is a syndrome?
A syndrome is a group of signs and symptoms that, added together, suggest a particular medical condition. In epilepsy, examples of these signs and symptoms would be things like the age at which seizures begin, the type of seizures, whether the child is male or female and whether they have physical or learning disabilities, or both. The results of an electroencephalogram (EEG) are also used to help identify epilepsy syndromes.
If you would like to know more about an epilepsy syndrome, please speak to your doctor. If you would like to know more about epilepsy in general, please contact Epilepsy Action.
Epilepsy Action would like to thank Dr Richard Appleton, consultant paediatric neurologist at Alder Hey Children’s Hospital, Liverpool, UK for preparing this information.