Letter to the Editor,
We read with interest Che et al.'s article on a 5-year-old male with a mitochondrial disorder (MID) due to the compound heterozygous variants c.451dupC and c.293C > T in MPV17 [1]. The mutation manifested phenotypically with hepato-cerebral mitochondrial depletion syndrome (MDS) with asymptomatic, non-specific fronto-temporo-occipital lesions and liver cirrhosis leading to liver failure [1]. Due to intractable liver failure, the patient underwent living donor transplantation, which was complicated by post-reperfusion syndrome (PRS) [1]. The PRS was successfully brought under control, the patient was extubated without complications and had an uneventful postoperative course [1]. The study is excellent, but some points need discussion.
The first point is that no family history was provided. We should know whether the two MPV17 variants were inherited from the father and mother or whether they occurred sporadically. We should also know whether either parent was clinically affected or not and whether there were other first-degree relatives suffering from MDS or other syndromic or non-syndromic MID.
A second point is that no sequencing of the mtDNA was performed. Since MPV17 variants can cause multiple mtDNA deletions or mtDNA depletion [2], it is imperative to investigate these types of mtDNA alterations. Until mtDNA depletion is genetically confirmed, MDS remains unproven. In this context, we should also know how liver mitochondria looked like at autopsy of the explanted liver. Were the liver mitochondria enlarged or reduced, increased or decreased in number, or did they have abnormal morphology.
A third point is that the description of cerebral magnetic resonance imaging (MRI) is incomprehensible [1]. Apparently, it showed lesions in a bilateral fronto-temporo occipital distribution, although this is not directly expressed [1]. We should know whether the cerebral MRI was actually abnormal and what kind of lesions were found if it was abnormal. This is significant because MPV17 variants usually manifest not only in the liver but also in the brain as hepato-cerebral syndrome [3]. We should also be informed whether the index patient had subtle neuropsychological deficits or other CNS manifestations.
A fourth point is that alternative causes of PRS have not been adequately considered. PRS can be due not only to low-temperature blood, lactic acidosis, inflammatory mediators, hyperkalemia, prolonged preoperative fasting with hypoglycaemia, or ATP depletion due to the secondary mitochondrial defect, but also to the medications administered during surgery. Since the patient underwent surgery for 10 h and received midazolam, ethomidate, sevoflurane, propofol, fentanyl, remifentanil, rocuronium, and cisatracurium, it is conceivable, that the sudden opening of the liver veins resulted in acute cardiotoxicity from these drugs due to the initial impairment of liver metabolism.
A fifth point is that the immunosuppressive drugs administered after transplantation have not been reported [1]. Because these medications can greatly influence the course and outcome of a patient's disease, it is important to know which medications the patient has received. Some of them, such as glucocorticoids, cyclosporine, or sirolimus, are known to cause myopathy [4,5]. We should also know whether the patient was evaluated for myopathy or rhabdomyolysis during follow-up.
A last point is that reference limits for blood parameters were not provided [1], making it difficult to assess whether a particular value was within or outside the normal range.
In summary, the excellent study has limitations that should be addressed before final conclusions are drawn. Clarifying the weaknesses would strengthen the conclusions and improve the study.
Consent to participation
Not applicable.
Consent for publication
Not applicable.
Ethical approval
Not applicable.
Funding
None received.
Author contribution
JF was responsible for the design and conception, discussed available data with coauthors, wrote the first draft, and gave final approval. SM: contributed to literature search, discussion, correction, and final approval.
Declaration of completing interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Guarantor
JF.
Acknowledgements
None.
Data availability
All data are available from the corresponding author.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data are available from the corresponding author.