Leigh Syndrome: Causes, Symptoms, Diagnosis and Treatment

Leigh syndrome, or commonly known as Leigh’s disease, is an inherited neurometabolic disorder characterized by progressive degeneration of the central nervous system (brain, optic nerves, and spinal cord). It usually affects infants between the age of three months and two years, but teenagers and adults may suffer from this disease as well.

What Causes Leigh Syndrome?

Leigh syndrome is caused by a defect in the function of mitochondria within the cells of the body. Mitochondria are the energy factories of the cells, which convert energy of glucose and fatty acids into a substance called adenosine triphosphate (ATP). The energy stored in the ATP is then used to perform almost all of the cell’s metabolic functions.

Mitochondria also carry its own DNA, called mitochondrial DNA (mtDNA). When irregular mutations take place in the mitochondrial DNA, the mitochondria become fail to function properly, which in turn affects the central nervous system and causes progressive degeneration of motor functions.

There is also a form of Leigh syndrome called X-linked Leigh’s disease which is result from mutations in a gene that produces other group of substances that are essential for cell metabolism.

In X-linked Leigh’s disease, genetic mutations occur on the x (female) chromosome. Males have one X chromosome and one Y chromosome, so a mutated gene on the X chromosome is sufficient to cause Leigh syndrome. Females have two X chromosomes, so a mutated gene on one X chromosome generally have less effect on a woman because of the non-mutated copy of the same gene on the other X chromosome.

A woman with a gene mutation on one X chromosome will be a carrier. On average, 50% of her sons will inherit the mutation and develop Leigh syndrome, and 50% of her daughters will inherit the mutation and become a carrier.

What are the Symptoms of Leigh Syndrome?

Symptoms of Leigh syndrome usually progress rapidly. Since the disease affects central nervous system, initial signs of Leigh syndrome may include poor sucking ability, loss of head control and motor functions. Loss of appetite, irritability, vomiting, continuous crying (in infants), and seizures may sometimes accompany these symptoms.

As Leigh syndrome becomes worse, symptoms may also include:

  • Generalized weakness
  • Heart problems
  • Low muscle tone (hypotonia)
  • Breathing difficulty
  • Episodes of lactic acidosis (accumulation of lactic acid in the body and brain) which may impair respiratory and kidney function.

How is Leigh Syndrome Diagnosed?

The diagnosis of Leigh syndrome is usually made based on the clinical symptoms that are confirmed thorough clinical evaluation and a variety of specialized tests, particularly imaging tests.

A magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain may reveal abnormal areas in certain parts of the brain. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures.

In some individuals, genetic testing may be able to confirm the presence of a genetic mutation.

How is Leigh Syndrome Treated?

Treatment of Leigh syndrome usually includes vitamin B1 (thiamine). Oral sodium bicarbonate or sodium citrate may also be prescribed to treat lactic acidosis.

The researchers are currently testing dichloroacetate to examine its effectiveness in treating lactic acidosis.

For people who have the X-linked Leigh’s disease, a low-carbohydrate and high-fat diet may be recommended. Other treatments may focus on the symptoms present, such as anti-seizure drugs or heart or kidney medicines.

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