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Reprint of: Diabetes in Kearns-Sayre Syndrome: More Common than Anticipated
Can J Diabetes 40 (2016) 109
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Letter to the Editor
Reprint of: Diabetes in Kearns-Sayre Syndrome: More Common than Anticipated This article was originally published in the August 2015 issue of the Canadian Journal of Diabetes. To the Editor: With interest, we read the article by Ho et al about 2 patients with Kearns-Sayre syndrome (KSS) who developed diabetes mellitus at an early stage of the disease but died because of cardiac involvement 6 and 2 years after onset of diabetes (1). We have the following comments and concerns. Contrary to the statement in the abstract, diabetes mellitus is not a rare phenotypic feature of KSS. When screening PubMed for publications about KSS during the past 5 years (2009 to 2014), 80 cases of KSS were found. To 16 papers, no access was available. Among the remaining 64 cases, diabetes was reported in 12 (19%). In 2 separate reports, 13% and 14% of patients with KSS had diabetes (2,3). In addition, diabetes may occur not only in syndromic mitochondrial disorders (MIDs), such as Wolfram syndrome, maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), KSS, thiamine-responsive megaloblastic anemia, Leigh syndrome, neuropathy, ataxia, retinitis pigmentosa (NARP), myoclonic epilepsy with ragged-red fibres (MERRF), Pearson syndrome and Leber hereditary optic neuropathy, but it occurs more commonly in patients with nonsyndromic MIDs (4). KSS is obligatorily associated with atrioventricular block or cardiomyopathy. Were either of the patients presented seen by a cardiologist at onset of diabetes? Patients with KSS commonly develop atrioventricular block during the disease course and require pacemaker implantation. Was an atrioventricular block or any other electrocardiographic abnormality present on routine surface electrocardiogram at onset of diabetes or shortly before the patients’ demise? Did either of the 2 patients develop ventricular arrhythmias requiring implantation of an intracardiac device? It should be mentioned that KSS may be due not only to mtDNA deletions but, rarely, also may be due to mtDNA point mutations (5) or to mutations in the RRM2B gene (6). Sweating is an unusual phenotypic manifestation of KSS but may be a prominent phenotypic feature in mitochondrial neurogastrointestinal encephalopathy (MNGIE) or nonsyndromic mitochondrial disorders.
We also have a few additional questions related to the cases presented. Patient 1 presented with developmental delay. Cerebral abnormalities are increasingly recognized in patients with KSS. Did he also undergo cerebral MRI? Did he present with basal ganglia calcification or hyperintensities of the basal ganglia, in particular the caudate nucleus and the globus pallidus, as has been previously reported (7)? Did he show a pattern of hyperintensities as in Leigh syndrome? Patient 2 died from cardiomyopathy. Which type of cardiomyopathy was diagnosed? It would be interesting to know whether there was any indication of cardiac involvement at the onset of diabetes in this patient. Overall, these 2 interesting cases show that the pathophysiology of diabetes mellitus in KSS is heterogeneous. Diabetes in KSS appears to be much more common than has been anticipated. Josef Finsterer, MD, PhD Marlies Frank, MD Krankenanstalt Rudolfstiftung, Vienna, Austria
References 1. Ho J, Pacaud D, Rakic M, Khan A. Diabetes in pediatric patients with KearnsSayre syndrome: Clinical presentation of 2 cases and a review of pathophysiology. Can J Diabetes 2014;38:225–8. 2. Khambatta S, Nguyen DL, Beckman TJ, Wittich CM. Kearns-Sayre syndrome: A case series of 35 adults and children. Int J Gen Med 2014;7:325–32. 3. Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf) 1992;37:97–103. 4. Daruich A, Matet A, Borruat FX. Macular dystrophy associated with the mitochondrial DNA A3243G mutation: pericentral pigment deposits or atrophy? Report of two cases and review of the literature. BMC Ophthalmol 2014;14:77. 5. Wang ZX, Yuan Y, Gao F, et al. Mitochondrial DNA mutations in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003;20:273–8. 6. Pitceathly RD, Fassone E, Taanman JW, et al. Kearns-Sayre syndrome caused by defective R1/p53R2 assembly. J Med Genet 2011;48:610–17. 7. Serrano M, García-Silva MT, Martin-Hernandez E, et al. Kearns-Sayre syndrome: Cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features. Mitochondrion 2010;10:429–32.
1499-2671 © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjd.2016.03.005
Contents lists available at ScienceDirect
Canadian Journal of Diabetes journal homepage: w w w. c a n a d i a n j o u r n a l o f d i a b e t e s . c o m
Letter to the Editor
Reprint of: Diabetes in Kearns-Sayre Syndrome: More Common than Anticipated This article was originally published in the August 2015 issue of the Canadian Journal of Diabetes. To the Editor: With interest, we read the article by Ho et al about 2 patients with Kearns-Sayre syndrome (KSS) who developed diabetes mellitus at an early stage of the disease but died because of cardiac involvement 6 and 2 years after onset of diabetes (1). We have the following comments and concerns. Contrary to the statement in the abstract, diabetes mellitus is not a rare phenotypic feature of KSS. When screening PubMed for publications about KSS during the past 5 years (2009 to 2014), 80 cases of KSS were found. To 16 papers, no access was available. Among the remaining 64 cases, diabetes was reported in 12 (19%). In 2 separate reports, 13% and 14% of patients with KSS had diabetes (2,3). In addition, diabetes may occur not only in syndromic mitochondrial disorders (MIDs), such as Wolfram syndrome, maternally inherited diabetes and deafness (MIDD), mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), KSS, thiamine-responsive megaloblastic anemia, Leigh syndrome, neuropathy, ataxia, retinitis pigmentosa (NARP), myoclonic epilepsy with ragged-red fibres (MERRF), Pearson syndrome and Leber hereditary optic neuropathy, but it occurs more commonly in patients with nonsyndromic MIDs (4). KSS is obligatorily associated with atrioventricular block or cardiomyopathy. Were either of the patients presented seen by a cardiologist at onset of diabetes? Patients with KSS commonly develop atrioventricular block during the disease course and require pacemaker implantation. Was an atrioventricular block or any other electrocardiographic abnormality present on routine surface electrocardiogram at onset of diabetes or shortly before the patients’ demise? Did either of the 2 patients develop ventricular arrhythmias requiring implantation of an intracardiac device? It should be mentioned that KSS may be due not only to mtDNA deletions but, rarely, also may be due to mtDNA point mutations (5) or to mutations in the RRM2B gene (6). Sweating is an unusual phenotypic manifestation of KSS but may be a prominent phenotypic feature in mitochondrial neurogastrointestinal encephalopathy (MNGIE) or nonsyndromic mitochondrial disorders.
We also have a few additional questions related to the cases presented. Patient 1 presented with developmental delay. Cerebral abnormalities are increasingly recognized in patients with KSS. Did he also undergo cerebral MRI? Did he present with basal ganglia calcification or hyperintensities of the basal ganglia, in particular the caudate nucleus and the globus pallidus, as has been previously reported (7)? Did he show a pattern of hyperintensities as in Leigh syndrome? Patient 2 died from cardiomyopathy. Which type of cardiomyopathy was diagnosed? It would be interesting to know whether there was any indication of cardiac involvement at the onset of diabetes in this patient. Overall, these 2 interesting cases show that the pathophysiology of diabetes mellitus in KSS is heterogeneous. Diabetes in KSS appears to be much more common than has been anticipated. Josef Finsterer, MD, PhD Marlies Frank, MD Krankenanstalt Rudolfstiftung, Vienna, Austria
References 1. Ho J, Pacaud D, Rakic M, Khan A. Diabetes in pediatric patients with KearnsSayre syndrome: Clinical presentation of 2 cases and a review of pathophysiology. Can J Diabetes 2014;38:225–8. 2. Khambatta S, Nguyen DL, Beckman TJ, Wittich CM. Kearns-Sayre syndrome: A case series of 35 adults and children. Int J Gen Med 2014;7:325–32. 3. Harvey JN, Barnett D. Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf) 1992;37:97–103. 4. Daruich A, Matet A, Borruat FX. Macular dystrophy associated with the mitochondrial DNA A3243G mutation: pericentral pigment deposits or atrophy? Report of two cases and review of the literature. BMC Ophthalmol 2014;14:77. 5. Wang ZX, Yuan Y, Gao F, et al. Mitochondrial DNA mutations in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2003;20:273–8. 6. Pitceathly RD, Fassone E, Taanman JW, et al. Kearns-Sayre syndrome caused by defective R1/p53R2 assembly. J Med Genet 2011;48:610–17. 7. Serrano M, García-Silva MT, Martin-Hernandez E, et al. Kearns-Sayre syndrome: Cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features. Mitochondrion 2010;10:429–32.
1499-2671 © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjd.2016.03.005