Authors: Ibrahim Elsharkawi, MD, Icahn School of Medicine—Mt. Sinai; Peter McGuire, MS, MD, National Institutes of Health (NIH); Shamima Rahman, FRCP, FRCPCH, PhD, UCL Great Ormond Street Institute of Child Health; Siobhan Climer, BS; Sophia Zilber, MA 

Reviewed: September 2023 

SUMMARY 

Leigh syndrome is a rare and severe neurometabolic disorder. With neurometabolic disorders, the nervous system does not work properly. This is due to problems with its chemical processes (metabolism). As a result, a range of neurological issues can occur. 

Leigh syndrome is a type of primary mitochondrial disease. This means it affects how mitochondria work. Mitochondria are cell structures that produce energy.  

This condition primarily affects babies and young children. Symptoms usually start between the ages of three months and two years. It can also occur in teenagers and adults. However, this is less common.  

Leigh syndrome is caused by a change in DNA. 

Leigh syndrome is also known as Leigh’s disease. 

Disorder Overview

DESCRIPTION

Leigh syndrome is a type of primary mitochondrial disease. Mitochondria are structures found in cells. They extract energy from food. This helps cells function. Every cell in the body (except red blood cells) has mitochondria.  

Primary mitochondrial disorders (PMDs) are a diverse group of conditions. They are caused by genetic changes.  

Mitochondria play a crucial role in converting food and oxygen into energy. In the case of Leigh syndrome, some mitochondria do not work properly. Specifically, this affects cells that supply energy to the brain, nerves, and spinal cord. 

Patients with Leigh syndrome have specific brain lesions. The presence of these lesions is key to diagnosis. These lesions typically appear in certain brain structures. This includes:  

• The basal ganglia 
• The brainstem 

Leigh syndrome affects at least 1 in 40,000 people. This number may be underestimated due to population variations, misdiagnosis, and other factors.  

Today, Leigh syndrome has no cure. The disease is progressive. It is likely to gradually worsen over time. Unfortunately, some individuals with Leigh syndrome do not survive beyond childhood. Others may have a longer lifespan but still face significant challenges.  

It is important to recognize that the outlook for Leigh syndrome varies per person. It may progress quickly or slowly. Some people are affected more severely than others.  

SIGNS AND SYMPTOMS

Early signs and symptoms of Leigh syndrome also occur with many other, more common, diseases. So, it is often difficult to diagnose Leigh syndrome when symptoms first start.  

Early problems may include: 

• Lack of appropriate weight gain 
• Poor feeding or sucking 
• Diarrhea and vomiting 
• Loss of motor skills or other developmental skills 
• Lethargy and drowsiness 
• Irritability or continuous crying 

As the disease progresses, symptoms typically become more apparent. They may include: 

Patients may not experience every symptom. These symptoms and complications are only possibilities.  

CAUSES

Leigh syndrome is caused by a genetic alteration. Over 110 genes can be affected. More genes are continuing to be discovered.  

Genes are part of DNA. A person has two types of DNA. Leigh syndrome can arise from changes in either type. They are: 

• Nuclear DNA. Nuclear DNA is found in the center (nucleus) of cells. Half of nuclear DNA is inherited from the father. Half is inherited from the mother. 
• Mitochondrial DNA. This DNA is found in mitochondria. Mitochondrial DNA is inherited from the mother alone. 

Leigh syndrome can be inherited. It can also occur spontaneously. When this happens, it is called “de novo.”  

There are four ways the gene mutation can be inherited. They are: 

Leigh syndrome inheritance is complicated. It is very important to consult with:  

• A geneticist  
• A licensed genetic counselor who has expertise in mitochondrial disorders 

They can properly explain the specific inheritance type that is relevant to your individual situation. 

LABORATORY INVESTIGATIONS

Healthcare providers use multiple methods to diagnose Leigh syndrome. These methods include: 

• Magnetic resonance imaging (MRI). MRI scans look for affected areas in the brain. 
• Blood tests. The doctor checks lactic acid levels and other metabolic markers.  
• Genetic tests. Tests could include a blood test, cheek swab, or urine sample. They allow the doctor to identify the type of gene mutation causing Leigh syndrome and confirm the diagnosis. 

Although Leigh syndrome is a genetic disease, a genetic change (variant) is not always able to be identified. In cases like this, additional testing may be recommended. This may include a muscle biopsy or skin biopsy. 

After diagnosis, the doctor may monitor many different labs and organ systems. They may refer the patient to specialists for comprehensive care.

TREATMENT AND THERAPIES

There is no known cure for Leigh syndrome today.  

Treatment is focused on:  

• Keeping children comfortable. 
• Slowing the progression of the disease. 
• Treating lactic acidosis. Lactic acidosis is a condition where there is too much lactic acid in the body. This causes symptoms like: 
  • Fatigue 
  • Muscle weakness 
  • Difficulty breathing 

Some doctors may recommend supplements. However, there is no definitive research that shows one supplement is better than another. So, recommendations may vary.  

Specific types of Leigh syndrome have specific, targeted treatments. These include:  

Often, children have trouble chewing and swallowing. It can be difficult to take in sufficient calories by mouth. This is especially true if they require increased calories. A feeding tube (also known as a gastrostomy tube or G-tube) can be helpful. It can improve caloric intake. It can also reduce the time needed for feeds.  

OUTLOOK

The outlook for Leigh syndrome varies widely. It is related to: 

• The specific genetic mutation 
• Age of onset 
• Severity of symptoms 

Some individuals have a relatively stable course with milder symptoms. Others experience rapid neurological decline and have a shortened lifespan.  

These are crucial in managing Leigh syndrome: 

• Close monitoring  
• Multidisciplinary medical care 

Caring for a child or loved one with a life-limiting condition like Leigh syndrome can be challenging. Caregivers may find it helpful to join a support group or talk with a mental health professional. 

Leigh Syndrome and Infections  

In some cases, Leigh syndrome can be triggered or worsened by infections. Particularly, respiratory infections like the flu or pneumonia can have this effect. This is because infections put additional stress on the body.  

People with Leigh syndrome may be more vulnerable to infections. This is because their immune systems are weakened by the condition. Take reasonable measures to prevent infections. For example, practice diligent handwashing and remain up to date with all age-recommended vaccinations.  

If an infection does occur, it is important to seek medical attention promptly. 

RELATED DISORDERS

Leigh syndrome may also be called: 

• Leigh’s disease or Leigh disease 
• Infantile subacute necrotizing encephalomyelopathy 
• Juvenile subacute necrotizing encephalomyelopathy 
• Subacute necrotizing encephalomyelopathy 

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Rahman S. Leigh syndrome. Handb Clin Neurol. 2023;194:43-63. https://doi.org/10.1016/b978-0-12-821751-1.00015-4. PMID: 36813320. 

Cleveland Clinic. Leigh Syndrome (Leigh’s Disease) [Internet]. 2022. Available from: https://my.clevelandclinic.org/health/diseases/6037-leigh-syndrome-leighs-disease. 

MedlinePlus. Leigh syndrome [Internet]. Bethesda, MD: National Library of Medicine. 2023 April. Available from: https://medlineplus.gov/genetics/condition/leigh-syndrome/. 

National Institute of Neurological Disorders and Stroke. Leigh Syndrome [Internet]. 2023. https://www.ninds.nih.gov/health-information/disorders/leigh-syndrome. 

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