This is a serious condition in which the nervous system cells begin to die. It is called Leigh syndrome and often happens due to an inherited gene or mitochondrial change. Usually, it causes seizures, developmental delays, heart problems, and respiratory issues. While most of the time, Leigh syndrome affects children, it may also happen in adults. Unfortunately, this syndrome cannot be cured. That’s why the treatment goal is to ease the symptoms and prevent life-threatening complications.
Furthermore, a baby who is born with Leigh syndrome seems healthy at birth, but over time, nervous system cells begin to degenerate or die, causing symptoms. Mostly, the symptoms appear in children between 3 months and 2 years old.
It can be caused by an abnormal gene that passes from biological parents to their children during pregnancy. Generally, Leigh syndrome is a type of mitochondrial disease that, most of the time, is fatal.
The classic form of Leigh syndrome negatively affects about 1 in 40,000 newborns in the world. Healthcare professionals do not fully understand why certain geographic populations are at increased risk for this disorder. For example:
- 1 in 2,000 newborns in the Saguenay Lac-Saint-Jean region of Quebec, Canada
- 1 in 1,700 newborns on the Faroe Islands, which are located between Iceland and Scotland
Types of Leigh Syndrome
Healthcare professionals have divided this syndrome into 3 categories. For example:
- Early-onset (infantile) – This is the most common form of this syndrome, and it often affects children before the age of 2. Sometimes, it is called classical Leigh syndrome or infantile necrotizing encephalopathy.
- Late-onset (adult-onset) – The symptoms of this form often appear after 2 years old, but may not happen until adolescence or early adulthood. In general, Leigh syndrome affects adults rarely. Usually, females are more likely to develop Leigh syndrome compared to males.
- Leigh-like syndrome – In such cases, people have symptoms that resemble Leigh syndrome, but imaging scans do not detect signs of the disease.
What is Mitochondrial Disease?
Certain small cellular structures that convert energy in fatty acids and glucose into a substance known as adenosine triphosphate (ATP). Thus, ATP energizes all body cells. In general, mitochondria are the body’s energy factories.
Approximately all body cells have mitochondria (except red blood cells). Mitochondrial diseases occur when mitochondria do not work properly. Damage to the cells usually occurs when the energy output of the cells diminishes. Normally, the nervous system requires a lot of energy to function. However, in people with Leigh syndrome, cells that produce energy are damaged or destroyed.
What Are The Symptoms of Leigh Syndrome?
The symptoms can be different among people with Leigh syndrome because they depend on several factors. Examples include the type and severity of the syndrome, age, and overall health. Check some early-onset symptoms below:
- Dysphagia (swallowing problems)
- Poor sucking or feeding issues
- Vomiting
- Diarrhea
- Hypotonia (low muscle tone)
- Poor head control and reflexes
- Irritability
- Long-term crying
When the disease progresses, it may cause additional symptoms that can also appear in people with late-onset type. For example:
- Muscle spasms
- Peripheral neuropathy
- Seizures
- Slowed physical growth
- Dementia
- Dystonia (involuntary muscle movements)
- Partial paralysis
- Dysarthria (slurred speech)
- Movement and balance problems (such as ataxia)
If you or your child has any of the previous symptoms, immediately contact your healthcare provider. Otherwise, it may lead to serious complications.
Causes
Healthcare providers have found about 75 genetic mutations that can cause Leigh syndrome. These abnormal genes negatively affect the body’s ability to produce ATP. Moreover, approximately 80% of children who develop Leigh syndrome inherit the abnormal gene in one of the following ways. For example:
- Autosomal recessive disorder – In this case, the child receives one abnormal gene from each biological parent. However, the parents do not have this condition because they are carriers.
- X-linked recessive genetic disorder – This type of inheritance makes the condition happen even with one abnormal gene on an X chromosome. This gene can passes form one of the biological parents. For instance, if one of the mother’s 2 X chromosomes has the abnormal gene, there is about a 25% chance of passing it to her son or daughter. Moreover, the daughter can pass this gene to her children in the future.
What Mitochondrial DNA Mutations Cause Leigh Syndrome?
Approximately 20% of children inherit a gene in the mitochondrial DNA (mtDNA) from their biological mother. This gene mutation often negatively affects every generation of a family. In rare cases, people can develop an mtDNA change spontaneously. Most of the time, the mtDNA change in Leigh syndrome keeps the MT-ATP6 gene from producing ATP.
What Are The Potential Complications of Leigh Syndrome?
People who develop Leigh syndrome may also experience some complications, especially if they do not get treatment. Check some of them below:
- Respiratory failure – This complication is one of the most common causes of death in people with Leigh syndrome. It commonly happens because of brainstem lesions that negatively affect breathing control.
- Neurological decline – This includes progressive loss of motor and intellectual disabilities, seizures, and dystonia.
- Metabolic crisis – This condition may also cause lactic acidosis (a buildup of lactate in the blood or cerebrospinal fluid).
- Movement disorders – For example, severe hypotonia (weak muscle tone), ataxia (balance problems), and spasticity.
- Gastrointestinal or feeding problems – Examples include severe dysphagia (severe swallowing problems), vomiting, diarrhea, and failure to thrive.
- Problems with sensory and other organs – Sometimes, people may also experience peripheral neuropathy, vision loss, hearing loss, cardiomyopathy, or kidney problems.
This article does not contain a full list of complications, but you can talk with your physician about ways to reduce the risk or even prevent them. In addition, there is no way to prevent Leigh syndrome. The only thing you can do is genetic tests to make sure you do not have the abnormal gene that causes it.
Diagnosis
The diagnosis of this genetic disorder begins with a physical examination to check for abnormalities linked to the disease. However, to confirm or exclude Leigh syndrome, doctors often perform the following tests. Examples include:
- Blood tests – These tests are used to check for lactic acidosis and enzyme markers that are often present in people with Leigh syndrome.
- Genetic test – This test also requires a blood sample to check for the abnormal genes that cause this syndrome.
- Imaging tests – Most of the time, physicians perform MRI (magnetic resonance imaging) scans to check for brain damage.
Treatment
The treatment goal is to relieve the symptoms, prevent life-threatening complications, and improve your child’s quality of life. However, doctors may recommend citric acid (sodium citrate) or sodium bicarbonate to treat lactic acidosis and thiamine (vitamin B1) to slow the disease progression. They will also recommend a high-fat and low-carbohydrate diet for children who have certain enzyme deficiencies.
It is also very important to consider the following steps because they help manage stress and lower the risk of mental disorders (such as anxiety or depression). For example:
- Healthy ways to reduce stress (such as focusing on a hobby or talking with a friend)
- Support groups
- Make time for yourself
- Supportive devices
Frequently Asked Questions
What are other names for Leigh syndrome?
This condition gets its name from the British physician Archibald Denis Leigh, who first described this syndrome in 1951. First, this condition was called subacute necrotizing encephalomyelopathy (SNE), but nowadays, most physicians use Leigh syndrome or Leigh’s disease.
How does Leigh syndrome affect vision?
Sometimes, this syndrome can affect the optic nerve and cause the following problems. These include:
- Strabismus (also known as crossed eyes)
- Optic atrophy (damage to the optic nerve)
- Eye weakness or paralysis
- Nystagmus (involuntary, incontrollable eye movements)
- Vision loss (blindness)
When should I visit a healthcare professional?
It is recommended to visit a doctor right away if you notice your child has any of the following symptoms. Examples include:
- Slowed physical growth
- Developmental delays or regressions
- Breathing, eating, or swallowing problems
- Seizures
Can Leigh syndrome affect adults?
Yes. Although Leigh syndrome most commonly develops in infants and young children, some people do not experience symptoms until adolescence or adulthood. Adult-onset Leigh syndrome is rare and may progress more slowly than the classic infantile form.
Is Leigh syndrome hereditary?
In most cases, yes. Leigh syndrome is usually caused by inherited genetic mutations that affect energy production in cells. Depending on the specific mutation, it can be inherited in an autosomal recessive, X-linked, or mitochondrial pattern. Sometimes, the mutation occurs spontaneously without a family history.
What is the life expectancy of someone with Leigh syndrome?
Life expectancy varies depending on the severity of the disease, the underlying genetic cause, and how early treatment begins. Unfortunately, classic infantile Leigh syndrome is often progressive and can be life-threatening. Many affected children develop serious complications within a few years of symptom onset. However, some individuals with milder forms may live longer.
Why does Leigh syndrome cause lactic acidosis?
Leigh syndrome affects the mitochondria, which are responsible for producing energy in cells. When mitochondria do not function properly, the body relies more on alternative pathways to generate energy, leading to an accumulation of lactic acid in the blood and tissues. This condition is known as lactic acidosis.
Can physical therapy help children with Leigh syndrome?
Yes. Physical therapy, occupational therapy, and speech therapy can help manage symptoms and improve quality of life. These therapies may assist with mobility, muscle strength, balance, communication skills, and daily activities, although they cannot stop disease progression.
Are there any experimental treatments for Leigh syndrome?
Researchers continue to study gene therapies, mitochondrial-targeted treatments, and other potential therapies for Leigh syndrome. While some experimental approaches show promise, there is currently no approved cure. Families interested in new treatment options should discuss clinical trials with their healthcare provider.
Can infections make Leigh syndrome symptoms worse?
Yes. Infections, fever, dehydration, and other physical stressors can increase the body’s energy demands and may worsen symptoms or trigger a metabolic crisis in people with Leigh syndrome. Prompt medical attention during illnesses is important to reduce the risk of complications. Ask your healthcare provider if you have additional questions.
