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NO pathway in the MELAS syndrome: An insufficiently explored and controversial research area
IJCA-23870; No of Pages 1 International Journal of Cardiology xxx (2016) xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
The L-arginine/NO pathway in the MELAS syndrome: An insufficiently explored and controversial research area Erik Hanff a, Arslan Arinc Kayacelebi a, Christoph Herrmann b, Mark Obermann b, Anibh Martin Das c, Dimitrios Tsikas a,⁎ a b c
Centre of Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany Centre for Neurology, Asklepios Hospitals Schildautal, Seesen, Germany Department of Pediatrics, Hannover Medical School, Hannover, Germany
a r t i c l e
i n f o
Article history: Received 21 October 2016 Accepted 2 November 2016 Available online xxxx
We thank Finsterer and Zarrouk-Mahjoub for their comments [1] on our letter [2]. We added [2] new information to the discussion raised recently in this journal [3,4] regarding the MELAS syndrome. Heteroplasmy is an essential factor in the context of mitochondrial disease. Blood leucocytes were positively analyzed for m.3243A NG point mutation [2]. Obviously, reported differences are due to distinct phenotypes of the MELAS syndrome with the m.3243A NG mutation. We reported a series of typical clinical features of our MELAS patient [2]. In addition, he showed several cardiac abnormalities: LV hypertrophy, open and hypermobile interatrial septum, intermittent SVES, and av bloc grade III with tachy-bradycardia. Oral L-arginine administration was 16 g/day; after 5 days a new stroke like episode happened, which showed a “non-vascular” pattern on MRI. Due to metformin intolerance [2] our MELAS patient did not receive this drug. A single case report [2] can only accomplish so much, as to guide the focus of future research in a particular direction, but may never be able
to answer any of the many still unresolved questions on its own. Indeed, the L-arginine/NO pathway in the MELAS syndrome is insufficiently explored and controversial. Further systematic investigations in larger patient cohorts are necessary in order to address remaining issues properly [1]. Unfortunately, Finsterer and Zarrouk-Mahjoub [1] neither clarified any of the reported issues in our case work up [2] nor added to the understanding of the L-arginine/NO pathway in the MELAS syndrome. The title of the letter [1] is purely speculative. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] J. Finsterer, S. Zarrouk Mahjoud, Levels of nitric oxide pathway parameters may depend on heteroplasmy rates of the m.3243ANG mutation, 2016. Int. J. Cardiol. http://dx.doi. org/10.1016/j.ijcard.2016.10.095 (in press). [2] E. Hanff, A.A. Kayacelebi, C. Herrmann, M. Obermann, A.M. Das, D. Tsikas, Unaltered Larginine/NO pathway in a MELAS patient: is mitochondrial NO synthase involved in the MELAS syndrome? Int. J. Cardiol. 223 (2016) 479–481. [3] J. Finsterer, S. Zarrouk Mahjoud, In the heart of MELAS syndrome, Int. J. Cardiol. 214 (2016) 157–158. [4] A.A. Youssef, U. Speiser, J. Schaefer, H. Reichmann, N. Richter, R.H. Strasser, S. Quick, Thinking beyond borders. Infective myocarditis on top of MELAS-cardiomyopathy first case description, Int. J. Cardiol. 203 (2016) 1020–1021.
⁎ Corresponding author at: Centre of Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. E-mail address: [email protected] (D. Tsikas).
http://dx.doi.org/10.1016/j.ijcard.2016.11.008 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: E. Hanff, et al., , Int J Cardiol (2016), http://dx.doi.org/10.1016/j.ijcard.2016.11.008
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
The L-arginine/NO pathway in the MELAS syndrome: An insufficiently explored and controversial research area Erik Hanff a, Arslan Arinc Kayacelebi a, Christoph Herrmann b, Mark Obermann b, Anibh Martin Das c, Dimitrios Tsikas a,⁎ a b c
Centre of Pharmacology and Toxicology, Hannover Medical School, Hannover, Germany Centre for Neurology, Asklepios Hospitals Schildautal, Seesen, Germany Department of Pediatrics, Hannover Medical School, Hannover, Germany
a r t i c l e
i n f o
Article history: Received 21 October 2016 Accepted 2 November 2016 Available online xxxx
We thank Finsterer and Zarrouk-Mahjoub for their comments [1] on our letter [2]. We added [2] new information to the discussion raised recently in this journal [3,4] regarding the MELAS syndrome. Heteroplasmy is an essential factor in the context of mitochondrial disease. Blood leucocytes were positively analyzed for m.3243A NG point mutation [2]. Obviously, reported differences are due to distinct phenotypes of the MELAS syndrome with the m.3243A NG mutation. We reported a series of typical clinical features of our MELAS patient [2]. In addition, he showed several cardiac abnormalities: LV hypertrophy, open and hypermobile interatrial septum, intermittent SVES, and av bloc grade III with tachy-bradycardia. Oral L-arginine administration was 16 g/day; after 5 days a new stroke like episode happened, which showed a “non-vascular” pattern on MRI. Due to metformin intolerance [2] our MELAS patient did not receive this drug. A single case report [2] can only accomplish so much, as to guide the focus of future research in a particular direction, but may never be able
to answer any of the many still unresolved questions on its own. Indeed, the L-arginine/NO pathway in the MELAS syndrome is insufficiently explored and controversial. Further systematic investigations in larger patient cohorts are necessary in order to address remaining issues properly [1]. Unfortunately, Finsterer and Zarrouk-Mahjoub [1] neither clarified any of the reported issues in our case work up [2] nor added to the understanding of the L-arginine/NO pathway in the MELAS syndrome. The title of the letter [1] is purely speculative. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] J. Finsterer, S. Zarrouk Mahjoud, Levels of nitric oxide pathway parameters may depend on heteroplasmy rates of the m.3243ANG mutation, 2016. Int. J. Cardiol. http://dx.doi. org/10.1016/j.ijcard.2016.10.095 (in press). [2] E. Hanff, A.A. Kayacelebi, C. Herrmann, M. Obermann, A.M. Das, D. Tsikas, Unaltered Larginine/NO pathway in a MELAS patient: is mitochondrial NO synthase involved in the MELAS syndrome? Int. J. Cardiol. 223 (2016) 479–481. [3] J. Finsterer, S. Zarrouk Mahjoud, In the heart of MELAS syndrome, Int. J. Cardiol. 214 (2016) 157–158. [4] A.A. Youssef, U. Speiser, J. Schaefer, H. Reichmann, N. Richter, R.H. Strasser, S. Quick, Thinking beyond borders. Infective myocarditis on top of MELAS-cardiomyopathy first case description, Int. J. Cardiol. 203 (2016) 1020–1021.
⁎ Corresponding author at: Centre of Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. E-mail address: [email protected] (D. Tsikas).
http://dx.doi.org/10.1016/j.ijcard.2016.11.008 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
Please cite this article as: E. Hanff, et al., , Int J Cardiol (2016), http://dx.doi.org/10.1016/j.ijcard.2016.11.008