Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis
Abstract 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...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-025-03588-5 |
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| Summary: | Abstract 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 = 0.001]. A negative linear correlation was observed between mutation load and age of onset in patients who presented with LS/LS+ (R2 = 0.592, P < 0.001), with the age of onset ranging from infancy to adulthood. Patients with an older age at onset [OR (95% CI), 1.46 (1.12–1.91), P = 0.005] or higher mutation loads [OR (95% CI), 1.14 (1.03–1.26), P = 0.011] were more likely to present with LHON/LHON+ than with LS/LS+. A total of 17 patients were documented as having received a combination of mitochondrial cofactor treatments. Compared with patients with LHON/LHON+, patients with LS/LS+ exhibited an exceedingly high probability of a stable or worsen outcome (93.8% vs. 33.3%, P = 0.006). 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. |
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| ISSN: | 1750-1172 |