[The molecular background of Leigh syndrome]

Abstract

Leigh syndrome (subacute necrotizing encephalomyopathy, MIM 256,000) is a progressive neurodegenerative disorder of infancy and childhood, with characteristic pathological hallmarks including symmetric necrotizing lesions in the brainstem, basal ganglia, thalamus and spinal cord. It may result from several defects of mitochondrial enzyme complexes, including pyruvate dehydrogenase complex, and respiratory chain complexes I, II, III, IV, V. Clinical presentation mostly includes failure to thrive, developmental delay, muscle weakness, hypotonia, disorders of ocular movements, abnormal respiratory rate and bulbar dysfunction. Symptoms usually start after a few months of normal development and the course is typically rapid and relentless. Affected patients usually die before 5 years of life due to central ventilation failure. Leigh syndrome occurs with an estimated frequency of 1:77,000-1:34,000 live births. The disease demonstrates maternal, X-linked, and autosomal recessive inheritance.