Leigh syndrome with leukodystrophy

Leigh syndrome with leukodystrophy (Orphanet code 255241) is an extremely rare mitochondrial disorder that combines features of Leigh syndrome (subacute necrotizing encephalomyelopathy) with prominent white matter abnormalities (leukodystrophy) visible on brain imaging. Leigh syndrome itself is a severe neurological condition characterized by progressive loss of mental and movement abilities, typically arising from defects in mitochondrial energy production. When accompanied by leukodystrophy, the disease involves not only the characteristic bilateral symmetric lesions in the brainstem and basal ganglia seen in classic Leigh syndrome, but also widespread abnormalities of the cerebral white matter, indicating additional or more extensive damage to myelin-producing cells. The condition primarily affects the central nervous system, with key clinical features including psychomotor regression or developmental delay, hypotonia (reduced muscle tone), dystonia, ataxia, feeding difficulties, respiratory abnormalities, and failure to thrive. Seizures and optic atrophy may also occur. Lactic acidosis is a common laboratory finding, reflecting impaired mitochondrial oxidative phosphorylation. The disease typically presents in infancy or early childhood and follows a progressive, often relapsing course that may be triggered by intercurrent illness or metabolic stress. There is currently no cure for Leigh syndrome with leukodystrophy. Treatment is primarily supportive and symptomatic, including nutritional support, management of seizures with anticonvulsant medications, physical therapy, and respiratory support as needed. Some patients may receive mitochondrial cofactor supplementation such as coenzyme Q10, thiamine, or riboflavin, although evidence for their efficacy remains limited. Prognosis is generally poor, with many affected individuals experiencing significant neurological decline in early life.

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