Leigh Syndrome

Leigh syndrome (LS) or subacute necrotizing encepha-lomyopathy, is genetically heterogenous, caused by mutations in the nuclear gene coding for SORF1 and mutations in the mitochondrial gene coding for ATPase 6. The inheritance is mendelian—autosomal recessive or X-linked recessive—or maternal. The biochemical defect results from defects in the OXPHO system and the pyruvate dehydrogenase complex.

The disease commonly affects infants and young children, rarely adolescents or adults. It presents with feeding difficulties, vomiting, hypotonia, oculomotor abnormalities, blindness and optic atrophy, seizures, and failure of psychomotor development. Central respiratory abnormalities, hypertension, and bouts of fever are characteristic. The pyruvate and lactate levels are elevated in the CSF. In older children, pyramidal, extrapyramidal, and cerebellar symptoms and mental retardation occur in various combinations. The disease progresses to death within 1 to 2 years of onset. The course may be slower and remitting in older patients. Hyperintense symmetric lesions in the putamens and brainstem tegmentum on T2-weighted MRI are helpful diagnostic clues. Magnetic resonance spectroscopy (MRS) shows increased lactic acid in the affected regions.

The lesions are typically symmetrically situated in the basal ganglia, diencephalon, midbrain, tegmentum of the pons and medulla, and the spinal cord. The mam-millary bodies are usually spared. Grossly, the affected regions are soft, brownish, often cystic and cavitated. The histology consists of spongiform degeneration of the neuropil, capillary endothelial hyperplasia and proliferation, and relative preservation of the neurons. Fat-laden macrophages are present in acute, and gliosis in chronic lesions. The optic nerves are often demyelinated.

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