Mitochondrial DNA mutations in late-onset Leigh syndrome.

Leigh syndrome (LS) is an early onset progressive neurodegenerative disorder with considerable clinical and genetic heterogeneities. Late-onset Leigh syndrome, i.e., onset after age of 2 years, is considered rare and often presents with atypical clinical features. We review the clinical features and imaging studies in a cohort of late-onset Leigh syndrome caused by mtDNA mutations. A total of 16 patients, 6 males and 10 females, were enrolled. The age at presentation was between 2 and 27 years of age. The first three clinical presentations found in our case series were ataxia, bulbar palsy, and pyramidal tract involvement, while disturbance of cognition and consciousness was less common. Six patients had both stroke-like episodes and seizures corresponding to the cortical lesions revealed on MRI. The most common lesion sites of basal ganglia and brainstem were putamen and midbrain, respectively. Dorsal aspects of the midbrain were the most vulnerable, especially periaqueductal region, and superior and inferior colliculus. Substantia nigra and red nuclei were involved less commonly. In our cohort, mutations of mtDNA in complex I were the commonest. In order of frequency, they were MT-ND3 (7/16), ND5 (3/16), ND6 (2/16), and ND1 (1/16). Causative mutations of MT-ATP6 were detected in the remaining three cases including 8993T>C, 9176 T>C, and 9185 T>C. Our study helps to define the types of clinical and neuroimaging finding in late-onset LS with the mutations of mtDNA. We expect to shed light on the identification of genotype-phenotype and genotype-neuroimaging correlations. On the other hand, our study highlights the importance of mtDNA mutations as a cause for LS, especially for late-onset cases.