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Low blood heteroplasmy-rate may cause late-onset MELAS
J. Finsterer, S. Zarrouk-Mahjoub
To cite this version:
J. Finsterer, S. Zarrouk-Mahjoub. Low blood heteroplasmy-rate may cause late-onset MELAS. Molec- ular Genetics and Metabolism Reports, Elsevier, 2017, 10, pp.100. �10.1016/j.ymgmr.2017.01.010�.
�hal-01565819�
Correspondence
Low blood heteroplasmy-rate may cause late-onset MELAS☆,☆☆,★
Keywords:
Mitochondrial Cardiomyopathy Myopathy Cardiac involvement Heart failure Sudden cardiac death
Letter to the Editor
The interesting article by Sunde et al. about a 54 yo female with MELAS due to the m.3243ANG mutation with a blood heteroplasmy- rate of 31% and manifesting with recurrent stroke-like episodes(SLEs), tonic-clonic seizures, migraine, hypothyroidism, short stature, fatigabil- ity, and hearing-loss[1]raises the following comments and concerns.
For epilepsy the patient was initially treated with levetirazetam, phenytoin, and lamotrigine[1]. Which was the daily dosage of each of these antiepileptic drugs(AEDs)? Why were three AEDs applied for pro- phylaxis? Which were the serum levels of these AEDs? From phenytoin it is well-known that it is mitochondrion-toxic[2]. Why was it nonethe- less given? Did seizures occur shortly before, during, or long after a SLE?
Was confusion after starting AEDs attributable to phenytoin?
Clonazapan is no AED. Do the authors mean clonazepam?
A heteroplasmy-rate of 31% in lymphocytes is low. Was heteroplasmy-rate determined also in other tissues, such as hair folli- cles, buccal mucosa, urinary epithelial cells, or muscle? Were heteroplasmy-rates higher in other tissues? Heteroplasmy-rates are re- ported to increase over time in post-mitotic tissues [3]. Were heteroplasmy-rates repeatedly determined during the disease course?
Did they indeed increase over time?
SLEs typically go along with a stroke-like lesion on cerebral MRI(cMRI)[4]. Did the patient ever undergo a cMRI during a SLE?
Was a characteristic vasogenic edema not concurring within a vascular territory seen in the acute stage?
Up to 25% of the mtDNA point mutations are sporadic with a family history negative for the disease[5]. Did the mother of the patient carry the mutation? Was hearing impairment the only clinical manifestation of MELAS in the mother? Which was the heteroplasmy-rate in the mother?
Overall, this interesting case could profit from discontinuation of phenytoin, from cMRI studies during a SLE, from genetic studies of the mother and her offspring, and from determination of the heteroplasmy-rates in tissues other than lymphocytes.
References
[1]K. Sunde, P.R. Blackburn, A. Cheema, J. Gass, J. Jackson, S. Macklin, P.S. Atwal, Case re- port: 5 year follow-up of adult late-onset mitochondrial encephalomyopathy with lactic acid and stroke-like episodes (MELAS), Mol. Genet. Metab. Rep. 9 (2016 Nov 18) 94–97.
[2] J. Finsterer, Toxicity of antiepileptic drugs to mitochondria, Handb. Exp. Pharmacol.
(Sep. 3 2016) (Epub ahead of print).
[3]A. Kowald, T.B. Kirkwood, Mitochondrial mutations and aging: random drift is insuf- ficient to explain the accumulation of mitochondrial deletion mutants in short-lived animals, Aging Cell 12 (2013) 728–731.
[4]J. Finsterer, Stroke and stroke-like episodes in muscle disease, Open Neurol J 6 (2012) 26–36.
[5] S.C. Sallevelt, C.E. de Die-Smulders, A.T. Hendrickx, D.M. Hellebrekers, I.F. de Coo, C.L.
Alston, C. Knowles, R.W. Taylor, R. McFarland, H.J. Smeets, De novo mtDNA point mu- tations are common and have a low recurrence risk, J. Med. Genet. (Jul. 22 2016) (pii:
jmedgenet-2016-103876)http://dx.doi.org/10.1136/jmedgenet-2016-103876.
Josef Finsterer1 Krankenanstalt Rudolfstiftung, Vienna, Austria Corresponding author at: Postfach 20, 1180 Vienna, Austria E-mail address:fipaps@yahoo.de.
Sinda Zarrouk-Mahjoub1 University of Tunis El Manar and Genomics Platform, Pasteur Institute of Tunis, Tunisia
18 January 2017 Molecular Genetics and Metabolism Reports 10 (2017) 100
1 Both authors contributed equally.
☆ There are no conflicts of interest
☆☆No funding was received
★ Author contribution: JF: design, literature search, discussion,first draft, SZ-M: litera- ture search, discussion, critical comments
http://dx.doi.org/10.1016/j.ymgmr.2017.01.010
2214-4269/© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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