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Inicio Neurología (English Edition) No MELAS syndrome without heteroplasmy levels or multisystem examination
Journal Information
Vol. 35. Issue 7.
Pages 521-522 (September 2020)
Vol. 35. Issue 7.
Pages 521-522 (September 2020)
Letter to the Editor
DOI: 10.1016/j.nrleng.2018.07.011
Open Access
No MELAS syndrome without heteroplasmy levels or multisystem examination
No se puede hablar de MELAS sin porcentaje de heteroplasmia ni investigación multisistémica
J. Finsterera,
Corresponding author

Corresponding author.
, C. Maeztub
a Krankenanstalt Rudolfstiftung, Messerli Institute, Veterinary University of Vienna, Vienna, Austria
b Division of Clinical Neurophysiology, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain
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Dear Editor:

It was with great interest that we read the case reported by Pérez Torre et al.1 of a 30-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome due to variant 3243A>G of the mitochondrial tRNA(Leu) gene. The patient presented unusual global cerebral involvement.1 We would like to comment on this case.

One limitation of the study is that it does not disclose the percentage of heteroplasmy. The cells of patients with MELAS usually display 2 different populations of mitochondria: some with wild-type mtDNA and others containing mutant mtDNA. If the number of mitochondria with mutant mtDNA exceeds a certain level, the patient will be symptomatic. In the light of the above, it would be interesting to know the percentage of heteroplasmy in hair follicle cells, oral mucosa cells, fibroblasts, muscle cells, and urinary tract epithelial cells of the patient presented by the authors. The percentage of heteroplasmy varies in accordance not only with the tissue analysed but also with the stage of the disease and between first-degree relatives.2

Furthermore, the patient received phenytoin (250mg/day) to treat seizures, but the authors do not indicate whether treatment was started after the first (January 2013) or the second epileptic episode (September 2013). It is also unclear when and why the patient started treatment with levetiracetam, lacosamide, and clonazepam. Phenytoin is known to cause mitochondrial toxicity and is therefore not recommended as the first-line treatment for patients with mitochondrial diseases.3 Furthermore, the authors do not explain why the patient received 4 different antiepileptic drugs. Were seizures refractory to treatment? May phenytoin have triggered status epilepticus originating in the occipital lobe? It would have been interesting to know how the status epilepticus was resolved. Did the patient start a ketogenic diet?

Another limitation of the case report is the lack of information on the patient's family history. Nearly two-thirds of mtDNA mutations are inherited by maternal transmission; we may therefore hypothesise that the mother either was affected or was an asymptomatic carrier. If the mother was not a carrier of the mutation, the authors should have determined whether the mutation detected in the patient was sporadic.

The high serum carnitine levels constitute another unusual finding.1 Most patients with primary mitochondrial diseases display secondary carnitine deficiency in the blood, which explains why some patients benefit from L-carnitine supplementation.4

Patients with MELAS syndrome present not only muscle and brain alterations, but also endocrine, cardiac, and gastrointestinal manifestations. Therefore, the study by Pérez Torre et al. should have disclosed whether the patient presented short stature, hypothyroidism, hypoparathyroidism, diabetes, hypoaldosteronism, hypocortisolism, or hypogonadism. Patients with MELAS syndrome should also be screened for such heart conditions as arrhythmia or cardiomyopathy, which have diagnostic and therapeutic implications: the literature reports an increased risk of sudden cardiac death among patients with MELAS syndrome5; intractable heart failure requires heart transplantation.6 There is also evidence that patients with mitochondrial diseases present greater risk of cardiac hypertrabeculation/left ventricular noncompaction cardiomyopathy,7 which can be complicated by heart failure, ventricular arrhythmia, and cardiopulmonary failure.

In summary, the study would have been more informative if authors had gathered genetic data on the patient and his first-degree relatives and screened for mild or subclinical manifestations of multisystemic disease. Mitochondrial diseases are frequently associated with multisystem manifestations, which may present at disease onset or appear during the course of the disease.

P. Pérez Torre, F. Acebrón-Herrera, N. García Barragán, Í. Corral Corral.
Global cerebral involvement and l-arginine use in a patient with MELAS syndrome.
B.O. Choi, J.H. Hwang, E.M. Cho, E.H. Jeong, Y.S. Hyun, H.J. Jeon, et al.
Mutational analysis of whole mitochondrial DNA in patients with MELAS and MERRF diseases.
Exp Mol Med, 42 (2010), pp. 446-455
J. Finsterer.
Toxicity of antiepileptic drugs to mitochondria.
Handb Exp Pharmacol, 240 (2017), pp. 473-488
L. Vallée, M. Fontaine, J.P. Nuyts, G. Ricart, I. Krivosic, P. Divry, et al.
Stroke, hemiparesis and deficient mitochondrial beta-oxidation.
Eur J Pediatr, 153 (1994), pp. 598-603
S. Seitun, L. Massobrio, A. Rubegni, C. Nesti, M. Castiglione Morelli, S. Boccalini, et al.
MELAS syndrome with cardiac involvement: a multimodality imaging approach.
Case Rep Cardiol, 2016 (2016), pp. 1490181
R.S. Bhati, B.C. Sheridan, M.R. Mill, C.H. Selzman.
Heart transplantation for progressive cardiomyopathy as a manifestation of MELAS syndrome.
J Heart Lung Transplant, 24 (2005), pp. 2286-2289
G. Limongelli, M. Tome-Esteban, C. Dejthevaporn, S. Rahman, M.G. Hanna, P.M. Elliott.
Prevalence and natural history of heart disease in adults with primary mitochondrial respiratory chain disease.
Eur J Heart Fail, 12 (2010), pp. 114-121

Please cite this article as: Finsterer J, Maeztu C. No se puede hablar de MELAS sin porcentaje de heteroplasmia ni investigación multisistémica. Neurología. 2020;35:521–522.

Copyright © 2018. Sociedad Española de Neurología
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