Leigh syndrome

Leigh syndrome, also known as subacute necrotizing encephalomyelopathy, is a severe progressive neurometabolic disorder characterized by bilateral symmetric necrotizing lesions in the basal ganglia, thalamus, brainstem, and spinal cord. It is one of the most common mitochondrial diseases in childhood and results from defects in mitochondrial energy production, specifically in the oxidative phosphorylation (OXPHOS) pathway or the pyruvate dehydrogenase complex. Over 100 genes — encoded by both nuclear DNA and mitochondrial DNA — have been implicated, making Leigh syndrome genetically highly heterogeneous. The disease primarily affects the central nervous system but can also involve the heart, liver, kidneys, gastrointestinal tract, and skeletal muscle. Key clinical features include psychomotor regression or developmental delay, hypotonia, ataxia, dystonia, respiratory abnormalities (including episodic hyperventilation or apnea), feeding difficulties, failure to thrive, and progressive neurological deterioration. Lactic acidosis in blood and/or cerebrospinal fluid is a hallmark biochemical finding. Characteristic bilateral symmetric lesions on brain MRI are a defining diagnostic feature. Episodes of metabolic decompensation, often triggered by intercurrent illness or fasting, can lead to rapid clinical decline. There is currently no cure for Leigh syndrome. Treatment is largely supportive and symptomatic, including nutritional support, management of seizures, physical therapy, and avoidance of metabolic stressors. Some patients may benefit from cofactor supplementation such as thiamine, coenzyme Q10, riboflavin, or biotin, depending on the underlying genetic defect, though evidence for efficacy is limited. Prognosis is generally poor, with many affected individuals dying in early childhood, although milder and later-onset forms have been described. Clinical trials investigating novel therapies, including gene therapy and small molecule approaches, are ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Leigh syndrome