Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.
Leigh syndrome is a rare genetic disorder that usually appears before a child turns two years old. It is also possible for Leigh syndrome to appear later in childhood or even in adulthood, and it usually progresses more slowly in these cases.
Leigh syndrome, also known as subacute necrotizing encephalomyelopathy (SNEM), affects about 1 in 40,000 newborns worldwide. It’s more common in a few places like Quebec’s Saguenay-Lac-Saint-Jean region and the Faroe Islands. This is likely due to a “founder effect,” where certain genetic mutations are enriched in these isolated communities, raising the chances of the syndrome.
Leigh syndrome is a genetic condition that disrupts the brain, spinal cord, and optic nerves by limiting the energy that cells need to function properly. This energy shortage comes from mutations in genes that affect the mitochondria, eventually leading to the neurological deterioration seen in Leigh syndrome. Mitochondria are the power producers of the cell, responsible for converting oxygen and nutrients into usable energy in the form of a molecule called ATP (adenosine triphosphate).Â
In the brain, energy is essential for areas that control movement, breathing, and coordination. When these brain areas don’t get enough energy, they weaken, leading to issues with muscle control, and breathing difficulties.
The spinal cord also relies on mitochondrial energy to send signals between the brain and the body. A lack of energy here may cause muscle weakness and movement problems.
For the optic nerves, which require a lot of energy to work effectively, insufficient energy may lead to vision problems. This may result in blurriness, involuntary eye movements, or even vision loss in severe cases.
Mitochondria are like small power plants within most cells in our body, excluding red blood cells. They produce roughly 90% of the energy our body needs to survive and function correctly. This energy production happens by converting the food we eat and the oxygen we breathe into fuel that cells use to carry out their functions.
When mitochondria do not function properly, cells don’t get the energy they need to work. This energy shortage may lead to mitochondrial diseases, where variousparts of body may struggle to function, often resulting in severe health issues. Leigh syndrome is one such condition, where a mitochondrial dysfunction prevents the brain and muscles from receiving the adequate amount of energy, causing progressive neurological and other symptoms.
Leigh syndrome is mainly caused by genetic mutations in over 110 different genes, mainly found in nuclear DNA. This type of DNA is located in the cell nucleus and holds most of our genetic information.One common example is the SURF1 gene. This gene is crucial for assembling complex IV, a vital part of how cells produce energy. When the SURF1 gene is mutated, complex IV can become incomplete or nonfunctional, which affects the cell’s ability to generate energy properly.
Mitochondrial DNA mutations may affect all children of an affected mother, with varying symptoms.It is rare that the condition cis X-linked, thus affecting males more than females. About 20% of Leigh syndrome cases come from mutations in mitochondrial DNA (mtDNA), which is inherited only from the mother. Unlike nuclear DNA, which we get from both parents, mitochondrial DNA is passed down only through the maternal line. Mutations in mtDNA can negatively impact energy production in mitochondria. One such gene affected by mtDNA mutations is MT-ATP6. This gene helps make ATP (adenosine triphosphate), the main energy source for cells. Mutations in MT-ATP6 may lead to lower ATP levels, making it hard for cells to meet their energy needs, which contributes to the symptoms of Leigh syndrome.Â
Some cases of Leigh syndrome are linked to nuclear DNA mutations in the pyruvate dehydrogenase (PDH) complex. In these cases, the genes involved work at less than 10% of their normal level, which is critical for producing energy in cells. The pyruvate dehydrogenase complex helps change pyruvate, a product of glucose, into acetyl-CoA. This process is essential for energy production. When there are mutations in this complex, it can throw off the energy balance in cells, causing the serious symptoms of Leigh syndrome. Understanding these genetic factors is important for finding affected individuals and developing possible treatments for this difficult condition.
Symptoms typically begin between ages three months to two years, though some may only show signs later in childhood or, in rare cases, adulthood. Listed below are the common symptoms of Leigh Syndrome:Â
As energy production slows down, those who have Leigh Syndrome may become more sensitive to stimuli, leading to frustration and distress. Children with Leigh syndrome may exhibit increased irritability or changes in behavior. This can be linked to the neurological impact of the condition, as the brain’s ability to regulate emotions and responses is affected.
Children with Leigh syndrome often experience delays in reaching developmental milestones, such as sitting, crawling, or walking. As the brain struggles to produce enough energy, it cannot support the physical and cognitive development typically seen in healthy children.
As children with Leigh syndrome grow, they may lose previously acquired motor skills, like the ability to walk or use their hands. This happens because the brain and muscles do not receive enough energy to function properly. The neurological damage compromises the communication between the brain and muscles, leading to weakness and loss of coordination.
Muscle weakness is a common symptom of Leigh syndrome. This weakness stems from the lack of energy in muscle cells, making it difficult for the body to carry out normal activities. Those who have Leigh Syndrome may appear floppy or have trouble holding up their heads or sitting independently. Over time, this weakness may lead to increased fatigue and difficulty with physical activities.
Seizures are a serious symptom of Leigh syndrome and may vary in type and severity. They occur due to abnormal electrical activity in the brain, which is influenced by the energy deficit caused by the disorder. Seizures may present as convulsions, loss of consciousness, or unusual movements, and managing them often requires medical intervention.
The energy deficiency affects not just the muscles involved in feeding but also the brain’s hunger signals, leading to a struggle to maintain proper nutrition. This is one of the most common among infants and children with Leigh syndrome.Â
Vomiting may occur, often as a response to metabolic imbalances or gastrointestinal issues linked to the disorder. This symptom can make it harder to eat and drink, leading to worse health in those affected.
When energy production in the cells along the optic pathway is affected, it can make it harder for the brain to process what the eyes see. This may cause vision problems because the optic nerves, which are responsible for transmitting visual information from the eyes to the brain, are affected..
As a result, those with Leigh syndrome may experience poor eyesight or have trouble coordinating their eye movements. Respiratory Issues
Respiratory issues may arise from muscle weakness affecting breathing, or from neurological impairment that disrupts the brain’s control over respiratory functions. This may lead to challenges in maintaining enough oxygen levels and can require supportive measures.
Leigh syndrome is most often inherited in an autosomal recessive pattern, meaning a child needs to inherit two mutated gene copies, one from each parent to develop the condition. Carriers typically have one normal and one mutated gene but do not show symptoms, resulting in a 25% chance with each pregnancy for their child to inherit both mutated copies.Â
However, about 20% of cases are passed down through mitochondrial DNA, which comes from the mother. If a mutation is present, all her children may potentially be affected, although symptoms may vary in severity. Rarely the Leigh syndrome follows an X-linked recessive pattern, affecting males with the single mutated X chromosome, while females are less likely to show symptoms unless they inherit two mutated copies. Additionally, some cases arise from spontaneous mutations without any family history of the disorder.
Currently, there is no cure for Leigh syndrome, and treatment primarily focuses on managing symptoms and improving the quality of life for those affected. Treatment options may include:
Medications: There are certain medications that your healthcare providers may prescribe to manage specific symptoms associated with Leigh syndrome. For example, anticonvulsants may be used to control seizures, while muscle relaxants can help alleviate muscle spasticity. These medications are specific to the individual’s needs, aiming to improve their overall comfort and functioning.
Nutritional support:This practice is essential, particularly for those who struggle with feeding and weight gain. A registered dietitian may work with families to develop meal plans that meet the unique needs of the individual. In some cases, specialized diets, such as ketogenic diets, may be recommended to help improve energy production in cells.
Physical therapy: This treatment aims to enhance motor skills and improve mobility. Therapists work with individuals to strengthen muscles, increase flexibility, and develop coordination. Regular physical activity may help reduce stiffness and improve overall physical functioning, allowing those with Leigh syndrome to participate more actively in daily life.
Occupational therapy: Focuses on helping individuals develop skills necessary for daily living activities. This may include assistance with self-care tasks such as dressing, bathing, and feeding. Therapists can also provide adaptive tools and strategies to make these tasks easier, fostering greater independence and enhancing quality of life.
Speech therapy: Addresses communication challenges often faced by individuals with Leigh syndrome. Speech therapists work on improving language skills, articulation, and social communication. They may also provide support for swallowing difficulties, ensuring safe and effective feeding practices for those who experience related issues.
Genetic counseling: This is an important resource for families affected by Leigh syndrome. It provides information about the inheritance patterns of the condition, the risks for future children, and available support resources where families are helped to understand the implications of genetic testing and guide them through the emotional aspects of managing a genetic disorder.
