A rare de novo mutation, m.1630A>G, in the mitochondrial trnAVal (MT-TV) gene in a child with epilepsy
We are thankful for the insightful comments on our case report involving a young child with a mitochondrial disorder (MID) caused by the m.1630A>G variant in mitochondrial tRNAVal (MT-TV) (1,2). We would like to take this opportunity to address the concerns raised and provide additional context.
We did not perform ancillary tests such as positron emission tomography (PET), magnetic resonance spectroscopy (MRS), lumbar puncture, and neuronal tissue biopsy in this young patient after careful consideration of the child’s age, level of co-operation, and the risks and benefits associated with these procedures. Given these factors, we were unable to obtain specific laboratory indices from neuronal tissue and cerebrospinal fluid (CSF). Should the need arise in the course of the patient’s treatment, we will pursue these investigations and follow up with the corresponding results.
Regarding mitochondrial DNA (mtDNA) copy number, we detected 4,766 reads in the patient’s blood, with 348 reads showing mutation, and 1,244,079 reads in the urine, with 89,718 reads showing mutation. Due to the limited research on this specific gene locus and the lack of comparative data or reference ranges, we are unable to assess the significance of the mtDNA copy number at this time. This is an area we plan to explore in future research.
We did perform a thorough assessment of multisystem involvement in the patient. However, due to the focus of our report, we did not elaborate on these aspects. As of the submission of our manuscript, the patient had no obvious abnormalities outside the nervous system, including but not limited to the eyes, ears, heart, and metabolism.
In terms of treatment, the patient’s primary symptom is intractable epilepsy. Various antiepileptic drugs, including valproate sodium, levetiracetam, zonisamide, lacosamide, topiramate, and clobazam, have been tried with unsatisfactory results. The patient is currently experimenting with the ketogenic diet, which has not yielded significant improvement. We will continue to monitor the therapeutic response and may consider discussing the potential use of a mitochondrial cocktail therapy with the patient’s family.
We appreciate the readers for bringing to our attention the information on the fourth patient with the m.1630A>G variant. This was an oversight in our literature search, and we will be more vigilant in addressing such issues in future publications.
In conclusion, we acknowledge the limitations of our study and appreciate the suggestions made by the readers. We are committed to improving our research methodology and addressing these limitations in future investigations. The treatment of intractable epilepsy in m.1630A>G carriers remains a challenge, and we are open to exploring various therapeutic options, including the ketogenic diet and mitochondrial cocktails, to improve patient outcomes.
We thank you for the opportunity to respond to these important points and hope that our response clarifies the issues raised.
Acknowledgments
None.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Translational Pediatrics. The article did not undergo external peer review.
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-258/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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References
- Wang Q, Chen Y, Li J, et al. A rare de novo mutation, m.1630A>G, in the mitochondrial tRNAVal (MT-TV) gene in a child with epilepsy: case report and review of the literature. Transl Pediatr 2025;14:367-72. [Crossref] [PubMed]
- Finsterer J. Intractable epilepsy in m.1630A>G carriers should be treated with a ketogenic diet on a trial basis. Transl Pediatr 2025;14:1383-4. [Crossref]
