Leigh syndrome is a rare neurometabolic condition that occurs in certain infants during their first 12 months. Symptoms include a progressive loss of mental and physical abilities, and the condition is usually fatal within the first few years.
Leigh syndrome is a rare condition that causes degeneration of the central nervous system (CNS), which includes the brain and spinal cord. The condition is also known as Leigh’s disease, classical Leigh syndrome, and subacute necrotizing encephalomyelopathy.
The syndrome primarily affects infants in their first year of life. It can cause a rapid deterioration of motor skills and other symptoms such as vomiting and seizures.
This article focuses on Leigh syndrome, its symptoms, causes, and what to expect from treatment.
A note about sex and gender
Sex and gender exist on spectrums. This article will use the terms “male,” “female,” or both to refer to sex assigned at birth. Click here to learn more.
Leigh syndrome is a genetic condition, meaning that it occurs due to genetic alterations. These genetic variations can affect mitochondrial DNA or enzyme production. A person typically inherits these genetic variations from a parent, and the condition usually presents during the
The CNS includes the brain and spinal cord, so its deterioration can cause various symptoms. For example, it can cause a lack of motor control, loss of appetite, and poor sucking ability in the early stages.
Leigh syndrome can cause more severe symptoms as it progresses, such as lactic acidosis. This is where the body produces too much lactic acid, which can lead to breathing difficulties and kidney problems.
Estimates suggest that Leigh syndrome occurs in 1 in 36,000–40,000 births and usually begins between the ages of 3 months and 2 years. Some forms of the condition affect males and females in equal numbers. However, when Leigh syndrome is the result of X-linked traits, it affects twice as many males as females.
Evidence also notes that it occurs more frequently in certain populations. For example, it occurs in approximately 1 in 2,000 newborns in the Saguenay Lac-Saint-Jean region of Quebec, Canada, and approximately 1 in 1,700 individuals in the Faroe Islands.
In rare cases, Leigh syndrome can affect adolescents and young adults.
Leigh syndrome affects the CNS and typically causes symptoms to rapidly deteriorate after they begin. The National Organization of Rare Disorders (NORD) states that early signs of the condition include a loss of previously acquired motor skills. For example, an infant may lose their sucking ability or control of the head.
Other early signs of the syndrome can include:
- loss of appetite
- continuous crying
- frequent vomiting
- failure to grow or reach developmental milestones
In toddlers, early symptoms might also include:
- speech problems
- coordination difficulties, such as while running
- a loss of previously acquired intellectual ability
The disease can rapidly progress to cause symptoms that include:
- lack of muscle tone
- slow and stiff leg movements
- muscle spasms
- lactic acidosis
Leigh syndrome typically causes respiratory problems, such as difficulty breathing or temporarily being unable to breathe. It can also cause unusual eye movement and visual impairments. The disease can affect other organs, including the kidney and heart.
Leigh syndrome is a genetic condition, and evidence notes that people may inherit the condition in the following patterns:
- autosomal recessive inheritance
- maternal inheritance of mitochondrial DNA
- X-linked recessive inheritance
The condition is typically the result of
For example, most people inherit the condition in an autosomal recessive pattern. This means that both copies of the gene they inherit from their parents have alterations.
People may inherit a variant of the SURF1 gene. This gene provides instructions for a protein that is important in oxidative phosphorylation. This is a process where the body converts energy from food into a form that cells can use.
Mitochondrial DNA-associated Leigh syndrome is a subtype of the condition. It results from changes in mitochondrial DNA, which is responsible for ensuring that cells have sufficient energy to function.
X-linked Leigh syndrome is when a person inherits the condition through an alteration in a gene on the X chromosome, a sex chromosome. Males typically only have one X chromosome, so one variation is sufficient to cause the condition. Females require two altered copies of the gene to develop the condition.
A medical professional typically uses a combination of evaluating symptoms and medical tests to diagnose Leigh syndrome. For example, a doctor may use an MRI or CT scan to check the brain for signs of the condition.
They might also use blood or tissue sample tests to check for other signs, such as high levels of acid in the brain due to lactic acidosis or the absence of certain enzymes, including pyruvate carboxylase.
There is currently no cure for Leigh syndrome, but a team of specialists will treat the specific symptoms that are apparent in each individual. The team may include pediatricians, cardiologists, neurologists, audiologists, and eye specialists.
Healthcare professionals may use a combination of treatments to manage the symptoms and slow the progression of the condition. These may include:
- vitamin supplements, such as vitamin B1 or L-carnitine
- dietary changes to reduce malnutrition or enzyme deficiencies, such as a high fat, low carbohydrate diet
- sodium bicarbonate or citrate
- eye medications to improve vision
- breathing support
- antiepileptic drugs
- medications for movement problems
Research is ongoing to identify new forms of treatment for the condition. For example,
The outlook for people with Leigh syndrome is
Infants with certain mitochondrial deficiencies have the worst outlook, such as those without mitochondrial complex IV activity. A 2020 study found that those who develop the disease later have a more positive outlook than those who develop the condition early.
Leigh syndrome is a rare genetic condition that causes a rapid deterioration of the CNS. It usually affects infants in their first year of life.
Early symptoms of the syndrome include head movement difficulties and an inability to suck. Heart, kidney, and vision problems can develop later. The disease may lead to breathing problems, which become fatal.
Leigh syndrome results from genetic alterations that a child inherits from their parents. There is currently no cure for the condition, but several treatments are available to manage the symptoms.
In rare cases, some children may live for several years with the condition. Although very rare, Leigh syndrome can also develop in adolescents and young adults.