Leigh Syndrome (Leigh’s Disease)

What is Leigh syndrome (Leigh’s disease)?

Leigh syndrome (also called Leigh’s disease) is a rare genetic condition that affects your child’s central nervous system. A newborn with Leigh syndrome seems healthy at birth. Over time, cells in their nervous system break down or degenerate. Symptoms, such as feeding problems, seizures and continuous crying, tend to occur when your child is between 3 months and 2 years old.

An inherited gene change (mutation) causes Leigh syndrome. It’s a type of mitochondrial disease. Unfortunately, there isn’t a cure. The condition is fatal, with most children passing away by age 3. In rare instances, the condition develops during adolescence or adulthood.

What are mitochondrial diseases?

Mitochondria are your body’s energy factories. These tiny cellular structures convert the energy in fatty acids and glucose into a substance called adenosine triphosphate (ATP). This substance energizes cells.

All cells (except red blood cells) have mitochondria. Mitochondrial diseases occur when mitochondria don’t function as they should. As the energy output of cells diminishes, cell damage or death occurs. Your nervous system requires a lot of energy to function. Leigh syndrome damages or destroys cells in your child’s nervous system that provide energy to their brain, nerves and spinal cord.

What are other names for Leigh syndrome?

Leigh syndrome gets its name from British physician Archibald Denis Leigh, who first described the condition in 1951. He called the condition subacute necrotizing encephalomyelopathy (SNE). Encephalomyelopathy refers to diseases that affect the brain and spinal cord. Today, most healthcare providers use Leigh syndrome or Leigh’s disease when talking about this condition.

What are the types of Leigh syndrome (Leigh’s disease)?

The types of Leigh syndrome include:

• Early-onset (infantile): The most common form of Leigh syndrome appears before age 2. Providers also call it classical Leigh syndrome or infantile necrotizing encephalopathy. The condition affects boys and girls equally.
• Late-onset (adult-onset): Symptoms appear after age 2 and may not occur until adolescence or early adulthood. Adult-onset Leigh syndrome is rare. The condition affects more males than females. The disease progresses slower than the infantile type.
• Leigh-like syndrome: A person has some symptoms of Leigh syndrome but imaging scans don’t detect signs of the disease.

How common is Leigh syndrome (Leigh’s disease)?

Classic (early-onset) Leigh syndrome affects approximately 1 in 40,000 newborns worldwide. Experts aren’t sure why certain geographic populations are more at risk for Leigh syndrome.

The condition affects:

• 1 in 2,000 newborns in the Saguenay Lac-Saint-Jean region of Quebec, Canada.
• 1 in 1,700 newborns on the Faroe Islands located between Iceland and Scotland.

What causes Leigh syndrome (Leigh’s disease)?

Experts have identified mutations in more than 75 different genes that can cause Leigh syndrome. The gene mutations affect your body’s ability to make ATP.

An estimated 8 in 10 children with Leigh syndrome inherit the gene change that causes the condition through one of two ways:

• Autosomal recessive disorder: A child inherits the same gene mutation from each parent. The parents are carriers of the changed gene, but they don’t have the disease.
• X-linked recessive genetic disorder: A gene change on an X chromosome causes the condition. It can come from the biological mother or father. If one of the mother’s two X chromosomes has the gene change, there’s a 1 in 4 chance that her son or daughter will inherit the mutated gene. If a boy inherits the gene change, they’ll develop Leigh syndrome; a girl will not. However, a daughter can pass the defective gene to her future children. A father can pass a changed X chromosome to his daughter, but not to his son.

What mitochondrial DNA changes cause Leigh syndrome (Leigh’s disease)?

About 2 in 10 children inherit a change in mitochondrial DNA (mtDNA) from their mothers. Both boys and girls can inherit this gene change, which then can affect every generation of a family. Rarely, a spontaneous mtDNA mutation occurs. The most common mtDNA change in Leigh syndrome keeps the MT-ATP6 gene from making ATP.

What are the symptoms of Leigh syndrome (Leigh’s disease)?

Symptoms of Leigh syndrome typically appear within your infant’s first two years of life. At first, your baby may reach expected child development milestones like holding up their head. Then, they start to regress, losing these abilities or showing signs of physical or developmental delays.

Signs of early-onset Leigh syndrome include:

• Difficulty swallowing (dysphagia), poor sucking or feeding problems.
• Diarrhea and vomiting.
• Hypotonia (low muscle tone).
• Irritability and chronic crying.
• Poor head control and reflexes.

Other symptoms may occur as the disease progresses. These symptoms can also appear with late-onset Leigh’s disease, including:

• Dementia.
• Movement and balance problems like ataxia.
• Dysarthria (difficulty forming words).
• Dystonia (involuntary muscle contractions).
• Muscle spasms or spasticity.
• Partial paralysis.
• Peripheral neuropathy
• Seizures.
• Slowed physical growth.

How does Leigh syndrome (Leigh’s disease) affect vision?

Leigh syndrome can also affect eye nerves, leading to problems like:

• Crossed eyes (strabismus).
• Deterioration of the optic nerves (optic atrophy).
• Eye weakness or paralysis.
• Involuntary rapid eye movements (nystagmus).
• Vision loss.

Teens or adults with late-onset Leigh syndrome may experience color blindness and loss of central vision (low vision).

What are the complications of Leigh syndrome (Leigh’s disease)?

Leigh syndrome can lead to a buildup of lactic acid in your child’s bloodstream, causing lactic acidosis. Your body makes lactic acid when oxygen levels in cells get too low to aid metabolism (the breakdown of carbohydrates into energy). There may also be too much carbon dioxide in their blood.

Lactic acidosis and increased levels of carbon dioxide can lead to:

• Breathing problems like shortness of breath (dyspnea), apnea (pauses in breathing) and abnormal or rapid breathing (hyperventilation).
• Heart problems like hypertrophic cardiomyopathy (thickened heart muscle).
• Kidney problems.

How is Leigh syndrome (Leigh’s disease) diagnosed?

Your healthcare provider may order:

• Blood tests to check for lactic acidosis and enzyme markers that indicate Leigh syndrome.
• Imaging scans like an MRI to check for damaged areas of brain tissue (lesions).
• Genetic test (a type of blood test) to determine the type of gene change causing the condition.

How do providers treat Leigh syndrome (Leigh’s disease)?

There isn’t a cure for Leigh syndrome. Treatments focus on easing symptoms to keep your child comfortable. Unfortunately, the condition is fatal.

Your child may benefit from:

• Citric acid (sodium citrate) or sodium bicarbonate to treat lactic acidosis.
• Thiamine (vitamin B1) injections to slow disease progression.

Children with certain enzyme deficiencies may benefit from a high-fat, low-carbohydrate diet. Some children who struggle to eat may need tube feeding (enteral nutrition).

What can you do if your child has Leigh syndrome (Leigh’s disease)?

Caring for a child with a life-limiting condition is challenging. These steps can ease stress while lowering your risk of depression and anxiety:

• Find healthy ways to ease stress like calling a friend or focusing on a hobby.
• Join an in-person or virtual support group.
• Learn more about your child’s condition and their unique symptoms and prognosis.
• Make time for yourself.
• Seek support services for your child, such as home healthcare and rehabilitation services.
• Talk to a mental health professional.

Can you prevent Leigh syndrome (Leigh’s disease)?

If you have a child with Leigh syndrome, a genetic test can determine if you or your partner have a gene mutation that causes it. You may decide to meet with a genetic counselor to discuss ways to lower the risk of passing along the mutated gene to future generations.

What is the outlook for someone with Leigh syndrome (Leigh’s disease)?

Many children with Leigh syndrome pass away from respiratory failure by age 3. It’s rare for a child with early-onset Leigh syndrome to survive into their teen years. People with adult-onset Leigh syndrome can live past their 50s.

When should I call the doctor?

Call your child’s healthcare provider if your child has:

• Developmental delays or regressions.
• Difficulty breathing, eating or swallowing.
• Seizures.
• Slowed physical growth.

What should I ask my provider?

You may want to ask your healthcare provider:

• What caused my child to have Leigh syndrome?
• What treatments can help my child?
• What can I do at home to help my child?
• Should my partner and I get genetic testing?
• Should I look for signs of complications?

A note from Cleveland Clinic

When your child has a rare life-limiting illness, it’s helpful to seek care from experts familiar with the disease. Leigh syndrome can affect various parts of your child’s body, such as their brain, eyes and organs, like their heart and kidneys. You may need to see multiple specialists. These providers can help manage symptoms and connect you with supportive resources so you can enjoy your time with your child.