BACKGROUND: A correlation between various sites or types of mutations in mitochondrial DNA ND3 and the development of a specific mitochondrial disease or phenotype has yet to be fully established. METHODS: This study reports a rare case of adult-onset Leigh syndrome (LS) and Leber hereditary optic neuropathy and dystonia (LDYT) overlap syndrome caused by the m.10197G>
A mutation in ND3. A review of the literature was conducted to investigate the clinical spectrum, treatment and outcome resulting from the m.10197G>
A mutation. Phenotypes associated with the m.10197G>
A mutation were classified into three categories: LS/LS+ (LS-involved overlap syndrome), Leber hereditary optic neuropathy (LHON)/LHON+ (LHON-involved overlap syndrome) and other mitochondrial encephalopathies or presentations. RESULTS: A total of 84 participants (78 patients and 6 asymptomatic carriers) with the m.10197G>
A mutation retrieved from 33 articles and the patient whose case we reported were included in the review and meta-analysis. Among all the participants, 55.3% (47/85) and 28.2% (24/85) presented with LS/LS+ and LHON/LHON+, respectively. The median age at onset for LS/LS+ was significantly younger than that for LHON/LHON+ [median, (Q1-Q3), 3.0 (0.58-9.5) vs. 13.5 (5.75-41.75), P = 0.002]. A negative linear correlation was observed between mutation load and age of onset in patients who presented with LS/LS+ (R CONCLUSIONS: LS/LS+ and LHON/LHON+ are the predominant presentations of the m.10197G>
A mutation. An older age at onset and greater mutation load increases the probability of an LHON/LHON+ presentation. Patients presenting with LS/LS+ have an exceedingly high possibility of an unfavorable outcome. The identification of factors and outcomes associated with phenotypes in patients with the m.10197G>
A mutation facilitates the provision of improved prognostic counseling for patients and their family members who are carriers of this mutation.