Leigh’s disease is a rare and progressive neurometabolic disorder that primarily affects the central nervous system. This condition leads to the degeneration of brain tissue, the spinal cord, and the optic nerves over time. It is a type of mitochondrial disease, impacting the body’s cellular energy production. Mitochondria, often referred to as the “powerhouses” of cells, convert food into energy. When their function is impaired, cells, especially those in the brain, cannot produce enough energy, leading to cell injury and death.
The Genetic Causes of Leigh’s Disease
Leigh’s disease arises from mutations in genes responsible for energy production within the mitochondria. These genetic defects disrupt the cell’s ability to generate adenosine triphosphate (ATP), the primary energy currency. Over 75 different genetic mutations have been linked to Leigh’s disease.
Genetic defects causing Leigh’s disease can originate from two distinct sources: mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Mitochondrial DNA mutations are inherited exclusively from the mother, meaning only biological mothers can pass these specific genetic changes to their children. In contrast, nuclear DNA mutations, a more common cause, involve genes inherited from both parents.
The primary inheritance pattern for nuclear DNA mutations is autosomal recessive. This means an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. Parents who carry one copy of the mutated gene are typically unaffected but can pass the gene to their offspring. The disruption of mitochondrial function, whether due to mtDNA or nDNA mutations, leads to widespread cellular dysfunction and death, particularly impacting the energy-demanding cells of the brain and nervous system.
Recognizing the Signs and Symptoms
Symptoms of Leigh’s disease typically emerge within an infant’s first two years of life, though onset can vary. Initially, a baby might meet developmental milestones, but then regress, losing previously acquired motor skills or showing new signs of physical and developmental delays. This infantile onset often presents with a loss of head control, poor sucking ability, frequent vomiting, and persistent irritability. Seizures are also a common manifestation in affected infants.
Symptoms can also appear later in childhood, or rarely, during adolescence or adulthood, with a potentially slower progression. The manifestations of Leigh’s disease affect multiple systems. Neurological symptoms include general weakness, diminished muscle tone (hypotonia), and uncoordinated movements (ataxia).
Respiratory issues, such as episodes of apnea (temporary cessation of breathing), can also occur and are a significant concern. Other symptoms may include difficulty swallowing (dysphagia), heart muscle weakness (cardiomyopathy), and vision problems like optic atrophy or involuntary rapid eye movements (nystagmus). The progressive nature of these symptoms means they tend to worsen over time, leading to increasing neurological deterioration.
How Leigh’s Disease is Diagnosed
Diagnosing Leigh’s disease typically begins with a thorough clinical evaluation, where physicians assess the child’s presenting symptoms and gather a detailed family medical history. Given that early symptoms can resemble those of other childhood conditions, initial diagnosis can be challenging. This initial assessment guides subsequent diagnostic steps.
Neuroimaging plays an important role in confirming a diagnosis, particularly through magnetic resonance imaging (MRI) scans of the brain. These scans often reveal symmetrical lesions in certain brain regions. These characteristic patterns on an MRI are highly indicative of Leigh’s disease.
Metabolic testing further supports the diagnosis by identifying biochemical abnormalities. Elevated levels of lactate in the blood and cerebrospinal fluid are frequently observed, reflecting the underlying metabolic dysfunction. These tests help to pinpoint the cellular energy production issues.
Genetic testing provides definitive confirmation by identifying the specific mutation responsible for the condition. This testing can pinpoint mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), which confirms the diagnosis and helps determine the inheritance pattern.
Treatment and Management Strategies
Currently, there is no cure for Leigh’s disease. Treatment focuses on managing symptoms and providing supportive care to enhance the quality of life for affected individuals.
Symptomatic treatments are often employed to address metabolic imbalances. Medications like sodium bicarbonate or sodium citrate may be used to manage episodes of lactic acidosis, a common issue. Additionally, some individuals with specific genetic forms of Leigh’s disease may benefit from vitamin supplementation, such as thiamine (vitamin B1).
Supportive therapies are an important part of care. Physical therapy helps maintain or improve motor skills and muscle strength, while occupational therapy assists with adapting daily activities to a child’s changing abilities. Speech therapy addresses difficulties with swallowing and communication. These therapies aim to maximize functional independence.
Managing specific complications is also an effort. Anti-convulsant medications are used to control seizures, and respiratory problems may require supportive care. A multidisciplinary care team, including neurologists, geneticists, therapists, and nutritionists, collaborates to provide comprehensive and individualized care.