What is Leigh's Disease?
Leigh syndrome is a rare degenerative condition that affects the central nervous system. It tends to develop after the age of 3 months and causes progressive symptoms that affect motor skills, strength, appetite and behaviour.
Leigh syndrome may also be referred to as:
- Leigh’s disease
- classical Leigh syndrome
- necrotising encephalomyelopathy of Leigh’s syndrome
- subacute necrotising encephalopathy (SNE)
What are the symptoms of Leigh syndrome?
Symptoms most commonly develop between the age of 3 months and 2 years of age.
The first symptom to become apparent is the loss of motor skill, which might have already been acquired in older children. In younger children, babies may lose the ability to hold their head and it is common for them to experience difficulties with feeding.
Children with Leigh syndrome tend to suffer from delayed development and there may also be changes in their mood and behaviour. Irritability is very common and children may cry for prolonged periods of time.
Some children with Leigh syndrome have seizures and it can also cause persistent vomiting.
When Leigh syndrome develops later (after the age of 2) symptoms may include:
- trouble expressing yourself verbally (known as dysarthia)
- difficulty coordinating movements (known as ataxia)
- impaired cognitive function and deterioration of previously acquired skills
As the disease progresses, the following symptoms may also develop:
- general muscle weakness
- hypotonia (loss of muscle tone)
- muscle spasms
- stiffness in the muscles and joints
- delayed neurological progress
- respiratory problems, most notably apnoea, short rapid breaths and irregular breathing patterns
- dysphagia (difficulty swallowing)
- abnormal, quick eye movements
- crossed eyes
- impaired vision
- hypertrophy of the heart muscle
- weakness in the arms and legs
There are various subdivisions of Leigh syndrome and sometimes, the symptoms may vary slightly. X-linked infantile Leigh syndrome causes similar symptoms to classical Leigh syndrome. However, the symptoms of subacute necrotising encephalomyelopathy (adult-onset) may differ. In most cases, the vision is affected first and neurological symptoms develop slowly. Eventually, there may be issues such as involuntary movements and spasms and symptoms similar to those associated with dementia.
What causes Leigh syndrome?
Leigh syndrome can be caused by several types of genetic defects, which can be inherited through recessive and X-linked patterns. Genetic mutations discovered in the mitochondria may also be a possible cause. In some cases, there is no genetic involvement.
Classical Leigh syndrome follows an autosomal recessive pattern and it is linked to a number of different genes. In this case, the defects affect the production of enzymes, including pyruvate dehydrogenase. Mitochondrial DNA defects can be passed on from parents to their children. There is a recessive inheritance pattern, which means that the child must inherit a defective gene from each parent to have the syndrome. If only one gene is passed on, this means that the child will be a carrier, but they won’t have symptoms.
In cases of X-linked Leigh syndrome, males will inherit the disease if they are passed a defective X gene. As females have two X chromosomes, they will only be a carrier if they inherit a single defective gene.
Some experts believe that adult-onset Leigh syndrome may be passed through dominant inheritance and this means that only one defective gene needs to be inherited in order for the individual to develop the syndrome.
How common is Leigh syndrome?
Leigh syndrome is rare and it is estimated to affect around 1 in every 36,000-40,000 live births. Leigh syndrome affects both males and females and most cases are diagnosed in infants. Around 80 percent of cases are diagnosed as classical Leigh syndrome. X-linked Leigh syndrome and adult-onset Leigh syndrome (subacute necrotising encephalomyopathy) are much more common in males than females.
Disorders related to Leigh syndrome include:
- Wernicke syndrome: this causes loss of ability to control muscle movements, confusion and abnormalities related to the eyes
- Korsakoff syndrome: this is characterised by memory loss, which is significantly more noticeable than other neurological symptoms
How is Leigh syndrome diagnosed?
Leigh syndrome is diagnosed using clinical evaluation of symptoms and imaging scans, including MRI and CT scans. Scan images highlight abnormalities in the brain and enable doctors to see specific areas of the brain in great detail. Additional tests may also be used to detect cysts and measure levels of blood glucose and certain enzymes.
Treating Leigh syndrome
There is no single cure or effective treatment for Leigh syndrome and treatments usually vary according to their type and severity. Often, individuals are cared for by a team made up of specialists in different fields and therapists, including physiotherapists, who help to improve quality of life. If vision and hearing are impaired, eyecare specialists and audiologists can help.
The most common form of treatment is vitamin B1, also known as thiamine. It is common for patients to show positive signs after starting treatment and it may also help to slow the progression of symptoms slightly. In cases where a patient lacks the enzyme pyruvate dehydrogenase, changes in diet to include more fats and less carbohydrate-rich foods, may be recommended.