Dear Editor:
With interest we read the article by Keilland et al. about a 12 yo female with MELAS-syndrome due to the m.3291T > C mutation, manifesting as overlap between MELAS, MERRF, MNGIE, KSS, and CPEO [1]. We have the following comments and concerns.
Apparently, the m.3291T > C mutation does not manifest significantly in the heart [1]. Did the propositus undergo comprehensive cardiologic investigations, including echocardiography and long-term ECG-recordings? Hypertrophic and dilated cardiomyopathy as well as noncompaction, aortic root ectasia, and atrial fibrillation, frequent cardiological manifestations of mitochondrial disorders [2], may go subclinical for years [3]. Ventricular runs may remain asymptomatic when occurring during the night. Were cardiac abnormalities reported in any of the affected/unaffected family members?
Stroke-like episodes (SLEs) have a variable clinical presentation [4]. How did they manifest clinically in the presented patient? Did they also manifest with seizures? In which cerebral region did equivalent stroke-like-lesions occur? Which type of treatment was provided for SLEs? Did the frequency of SLEs decline after initiation of the vitamin-cocktail? Which remnants of the stroke-like-lesions were seen on MRI?
Topiramate is an inhibitor of the mitochondrial carboanhydrase-VB. Topiramate has beneficial [5] and unfavourable effects [6] to mitochondria. As an inhibitor of the mitochondrial transition pore it has an anti-obesity effect but can be also effective in migraine and epilepsy. Did the patient suffer from migraine, a frequent phenotypic manifestation of mtDNA mutations, and did migraine respond to topiramate? Why did she require two antiepileptic drugs in a relatively low dosage? Was reduced weight (35.7 kg at age 15 y) a side effect of topiramate?
The patient presented with clinical manifestations of KSS [1]. Which were the clinical manifestations of KSS? Was there an AV-block-III? Did she require a pacemaker? Was CSF protein elevated?
Overall, this interesting case report requires a detailed description of the phenotype, a more comprehensive cardiologic investigation, and an explanation of the antiepileptic regimen.
Footnotes
There are no conflicts of interest.
References
- 1.Keilland E., Rupar C.A., Prasad A.N., Tay K.Y., Downie A., Prasad C. The expanding phenotype of MELAS caused by the m.3291T > C mutation in the MT-TL1 gene. Mol. Genet Metab. Rep. 2016;6:64–69. doi: 10.1016/j.ymgmr.2016.02.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Finsterer J., Kothari S. Cardiac manifestations of primary mitochondrial disorders. Int. J. Cardiol. 2014;177:754–763. doi: 10.1016/j.ijcard.2014.11.014. [DOI] [PubMed] [Google Scholar]
- 3.Takeda A., Sudo A., Yamada M., Yamazawa H., Izumi G., Nishino I., Ariga T. Barth syndrome diagnosed in the subclinical stage of heart failure based on the presence of lipid storage myopathy and isolated noncompaction of the ventricular myocardium. Eur. J. Pediatr. 2011;170:1481–1484. doi: 10.1007/s00431-011-1576-5. [DOI] [PubMed] [Google Scholar]
- 4.Finsterer J. Stroke and stroke-like episodes in muscle disease. Open Neurol. J. 2012;6:26–36. doi: 10.2174/1874205X01206010026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Motaghinejad M., Motevalian M., Shabab B. Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in rat isolated hippocampus. Clin. Exp. Pharmacol. Physiol. 2016;43:360–371. doi: 10.1111/1440-1681.12538. [DOI] [PubMed] [Google Scholar]
- 6.Rinalduzzi S., Cipriani A.M., Accornero N. Topiramate and visual loss in a patient carrying a Leber hereditary optic neuropathy mutation. Neurol. Sci. 2012;33:419–421. doi: 10.1007/s10072-011-0755-5. [DOI] [PubMed] [Google Scholar]