Leigh syndrome (LS) is also called Leigh disease or subacute necrotizing encephalomyelopathy. LS is a progressive neurodegenerative disorder of infant or children, characterized by the psychomotor retardation, ataxia, hypotonia, involuntary movements, optic atrophy, brain stem dysfunction, lactic acidosis, and symmetric basal ganglia and brain stem lesions. The diagnosis of LS is based on characteristic neuropathologic findings of bilateral and symmetric necrotizing lesions in the basal ganglion and brain stem. Because many pediatricians are quite unfamiliar to LS, the authors summarize the characteristics of potients with LS, and detect mitochondrial DNA mutations in maternal inherited LS patients in the mainland of China.

The clinical features of 8 patients with LS were summarized and analyzed, including symptoms and signs, blood lactic acid and pyruvate level, blood gas analysis, CK level, cranial MRI, muscle biopsy and brain autopsy results, mitochondrial DNA (mtDNA) mutation analyses, and so on. Two clinical subtypes of LS, infantile form and juvenile form, were compared also in this work.

Five of 8 cases with the early onset before 1 year of age mainly presented progressive psychomotor retardation, hypotonia, intermittent abnormalities of the respiratory rhythm, convulsions, ophthalmoplegia, feeding and swallowing difficulties, auditory and visual dysfunction, and nystagmus. Three of 8 cases with onset after 1 year of age mainly presented walking disturbance, muscle weakness, ophthalmoplegia, cranial nerve signs, ataxia, hypertonia, positive pyramidal sign and convulsion. The blood lactic acid levels elevated in 7 cases. The MRI performed in 6 cases showed symmetric and bilateral basal ganglion and brain stem lesions, and characterized by high intensity on T2-weighted images and low intensity on T_1-weighted images. The putamen was most often involved, and also most severe. The volume loss of putamen and caudate nuclei were also found in 2 cases. Brain stem were involved in 3 cases. No typical ragged-red-fiber and other specific pathological changes were found in muscle biopsy samples of 2 cases. In 4 of 8 cases with autopsy, brain neuropathological examination showed multiple symmetrical foci of degeneration and necrosis, loss of neurons with capillary proliferation and dilation. These foci, of variable extent and topography, were mainly in brain stem, among them substantia nigra, vestibular nucleus, abducent nucleus, hypoglossal nucleus were seriously involved in all cases. Basal ganglia were involved in 2 cases, and putamens were affected most severely. The cerebellar, cerebral cortex and cerebral white matter involvement were found in 3, 2 and 2 cases, respectively. The mtDNA analyses were performed in 3 cases. The mtDNA nt 8993 T→G mutation was detected in 1 case and her mother who is healthy now, but not in his father. The point mutation was not detected in the other 2 cases.

The common characteristic signs of LS are progressive psychomotor retardation, hypotonia, intermittent abnormalities of the respiratory rhythm, convulsions, ophthalmoplegia, and so on in infant, and walking disturbance, muscle weakness, ophthalmoplegia, ataxia, hypertonia and so on in child. The typical finding on MRI was long T₁ long T₂ lesions in symmetric basal ganglion and brain stem. The clinical diagnosis of LS may be made according to typical clinical and MRI presentation, blood and/or CSF lactic acidosis before patient's death. Characteristic neuropathological finding in autopsy, especially in brain stem and basal ganglion can confirm the diagnosis. For maternally inherited LS, the mtDNA analysis can directly confirm the diagnosis before patient's death.

Leigh disease; Mitochondrial encephalomyopathies; Mutation