Leigh syndrome is a rare, severe inherited neurological disorder that primarily affects the central nervous system, including the brain, spinal cord, and optic nerves. It is characterized by the progressive degeneration of these areas. While it often manifests in infancy or early childhood, symptoms can sometimes emerge later in adolescence or adulthood.
Understanding Leigh Syndrome
Leigh syndrome is classified as a mitochondrial disease, meaning it disrupts the normal function of mitochondria, the energy-producing centers within nearly every cell. Mitochondria convert energy from food into adenosine triphosphate (ATP), the primary energy currency for cellular processes. When mitochondria do not function correctly, cells experience an energy deficiency, leading to damage or death. This energy deficit disproportionately impacts organs with high energy demands, such as the brain, muscles, and heart.
Recognizing the Symptoms
The symptoms of Leigh syndrome often begin with a regression of previously acquired developmental milestones. Infants may exhibit poor head control, diminished sucking ability, and difficulties with feeding, which can lead to failure to thrive. Irritability, continuous crying, and recurrent vomiting are also common early signs.
As the condition progresses, neurological symptoms become more apparent. These can include:
Hypotonia (low muscle tone), ataxia (lack of coordination), dystonia (involuntary muscle contractions), and seizures.
Visual impairments such as nystagmus (involuntary eye movements), ophthalmoparesis (weakness of eye muscles), and optic atrophy (degeneration of the optic nerve).
Respiratory problems, including episodes of apnea (temporary cessation of breathing), hyperventilation, and abnormal breathing patterns.
Cardiac involvement, such as hypertrophic cardiomyopathy (thickening of the heart muscle).
Genetic Basis
Leigh syndrome results from specific genetic mutations that interfere with mitochondrial function. Over 110 different genes have been associated with the condition, with most involved in the mitochondrial respiratory chain or the pyruvate dehydrogenase complex. These genetic alterations can occur in either nuclear DNA or mitochondrial DNA.
The most common inheritance pattern is autosomal recessive, where an individual inherits one mutated copy of a gene from each parent, who are typically unaffected carriers. Mitochondrial inheritance occurs when mutations are found in mitochondrial DNA, passed down exclusively from the mother. Less commonly, X-linked inheritance can occur, where the mutated gene is on the X chromosome, often affecting males more severely.
Diagnosis and Treatment
Diagnosing Leigh syndrome often involves a combination of clinical evaluation and specialized tests. Neuroimaging, such as an MRI of the brain, can reveal characteristic lesions in regions like the brainstem and basal ganglia. Metabolic testing may show elevated lactate levels in the blood or cerebrospinal fluid, indicating a metabolic dysfunction.
Definitive diagnosis is usually confirmed through genetic testing, which identifies specific gene mutations. While there is currently no cure for Leigh syndrome, management focuses on symptomatic and supportive care.
Nutritional support, including dietary interventions for feeding difficulties, is often a component of care. Some individuals may benefit from vitamin supplementation, such as thiamine or coenzyme Q10, depending on the underlying genetic defect. Management of seizures with anti-epileptic drugs, respiratory support, and physical or occupational therapy are also common approaches.
Outlook and Support
The prognosis for Leigh syndrome varies depending on the specific genetic cause and symptom severity. Life expectancy can differ significantly among individuals, with respiratory failure being a common cause of death in childhood. Early diagnosis allows for comprehensive supportive care, improving quality of life.
Support groups and patient advocacy organizations offer valuable resources for affected families, providing information and community. Ongoing research efforts, including clinical trials, continue to explore potential therapies and improve understanding of the disorder.