Maternally Inherited Diabetes and Deafness Is Phenotypically and Genotypically Heterogeneous: Response

Letters to the Editor 16. 17. 18. 19. 20. maternally inherited diabetes and deafness caused by the 3243A.G mutation of mitochondrial DNA. Cardiology. 2010;115:71-74. Mangiafico RA, Zeviani M, Bartoloni G, Fiore CE. Accelerated cardiomyopathy in maternally inherited diabetes and deafness. Int J Clin Pharmacol Res. 2004;24:15-21. Schleiffer T, 't Hart LM, Schürfeld C, Kraatz K, Riemann JF. Maternally inherited diabetes and deafness (MIDD): unusual occult exocrine pancreatic manifestation in an affected German family. Exp Clin Endocrinol Diabetes. 2000;108:81-85. Bergamin CS, Rolim LC, Dib SA, Moisés RS. Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10. Arq Bras Endocrinol Metabol. 2008;52:1345-1349. Narbonne H, Paquis-Fluckinger V, Valero R, Heyries L, Pellissier JF, Vialettes B. Gastrointestinal tract symptoms in maternally inherited diabetes and deafness (MIDD). Diabetes Metab. 2004;30:61-66. Cao XY, Wei RB, Wang YD, Zhang XG, Tang L, Chen XM. Focal segmental glomerulosclerosis associated with maternally inherited diabetes and deafness: clinical pathological analysis. Indian J Pathol Microbiol. 2013;56:272-275. Maternally Inherited Diabetes and Deafness Is Phenotypically and Genotypically Heterogeneous: Response W e welcome the comments and table provided by Professors Josef Finsterer, MD, PhD and Marlies Frank, MD in relation to our recent JNO publication (1). They provide further evidence of the highly heteroplasmic nature of maternally inherited diabetes and deafness (MIDD) because of the A3243G mitochondrial RNA mutation. Table 1 from their letter outlines several reports of multiple organ compromise associated with MIDD. In addition, we are also able to answer some of their questions. Our 2 patients did not have ptosis, and there was no clinical evidence of gastrointestinal or renal involvement. Laboratory test results of renal, hepatic, and gastrointestinal functions also were normal. Patient 2 was diagnosed with MIDD in 1993, the same year that the clinical phenotype was first reported. She was not seen by the authors for 14 years. When evaluated in 2007, she had been on pravastatin, 40 mg daily for 3 years. Although she did not complain of muscle weakness or pain and had no clinical evidence of myopathy, her creatinine phosphokinase (CPK) was elevated (1,074 U/L, normal: 30-135 U/L) but myoglobin was not present in the urine. Pravastin was discontinued, and we recommended avoiding future use of statins. Unfortunately, the patient changed residence over the years, with inadequate continuity of care; as a result, a new prescription for rosuvastatin, 20 mg daily, was prescribed sometime in 2012. One month later, she had severe rhabdomyolysis, which gradually improved. She did not contact us during this period of time, and we do not know the serum CPK level. Her muscle examination in 2013, approximately 1 year later, was normal, and the last 346 21. de Wit HM, Westeneng HJ, van Engelen BG, Mudde AH. MIDD or MELAS: that's not the question MIDD evolving into MELAS: a severe phenotype of the m.3243A.G mutation due to paternal co-inheritance of type 2 diabetes and a high heteroplasmy level. Neth J Med. 2012;70:460-462. 22. Naing A, Kenchaiah M, Krishnan B, Mir F, Charnley A, Egan C, Bano G. Maternally inherited diabetes and deafness (MIDD): diagnosis and management. J Diabetes Complications. 2014;28:542-546. 23. Bannwarth S, Abbassi M, Valéro R, Fragaki K, Dubois N, Vialettes B, Paquis-Flucklinger V. A novel unstable mutation in mitochondrial DNA responsible for maternally inherited diabetes and deafness. Diabetes Care. 2011;34:2591-2593. 24. Perucca-Lostanlen D, Taylor RW, Narbonne H, Mousson de Camaret B, Hayes CM, Saunieres A, Paquis-Flucklinger V, Turnbull DM, Vialettes B, Desnuelle C. Molecular and functional effects of the T14709C point mutation in the mitochondrial DNA of a patient with maternally inherited diabetes and deafness. Biochim Biophys Acta. 2002;1588:210-216. 25. Chen FL, Liu Y, Song XY, Hu HY, Xu HB, Zhang XM, Shi JH, Hu J, Shen Y, Lu B, Wang XC, Hu RM. A novel mitochondrial DNA missense mutation at G3421A in a family with maternally inherited diabetes and deafness. Mutat Res. 2006;602:26-33. CPK was only modestly elevated at 150 U/L (normal: 30- 135 U/L). Since then, her mild cholesterol elevation has been managed primarily with diet control. In relation to additional neurologic symptoms and findings, neither one of our patients has developed acute complications mimicking mitochondrial encephalopathy, lactic acidosis and stroke (MELAS) nor do they report disabling headaches. Both patients had a normal mini- mental status when last examined, and Patient 1 retired from work. Patient 2 has been successfully using a monaural cochlear implant for 22 years, learned how to communicate very efficiently during regular conversation, and raised a family. The question of central nervous system structure-function in this disorder is interesting; one would anticipate greater neurologic impairment considering the imaging findings. To answer this question, one must hypothesize that brain plasticity in response to overt mitochondrial-related structural, neuronal, or glial change has provided effective cognitive, sensory, and motor compensation. Moreover, our 2 patients did not have long-tract sensory signs, and the only sensory abnormality found was decreased pin prick in a stocking distribution in Patient 1. Evoked potentials were not performed. The white-matter signal changes and cerebral/cerebellar atrophy noted on magnetic resonance imaging (MRI) are likely due to gliosis and neuronal loss; they coincide with tissue calcification on computed tomography in Patient 2 and do not bear similarity to the larger MRI hemispheric lesions found in the classic MELAS phenotype. Cerebral MRI spectroscopy would have been of interest, but was not performed since the diagnosis has been made from the muscle biopsy. Finsterer and Frank also raise an important point in reference to the MIDD genotype; other mitochondrial mutations may be responsible; thus, the tissue analysis Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 343-352 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor should be comprehensive if the transfer RNA A/G 3243 mutation is not found. Finally, we agree with the need to proactively test patients with MIDD for subclinical organ failure. Patients with MIDD are eligible for care at muscular dystrophy clinics, where there may be a monetary supplement to their private insurance. Although there is no cure for this disorder at the present time, preventive care may impact substantially on the quality of life. Jorge C. Kattah, MD Department of Neurology/Neurophthalmology, Illinois Neurologic Institute, University of Illinois College of Medicine at Peoria, Peoria, Illinois Palinopsia: Side Effect of Topiramate and Acetazolamide W e read with interest the recent articles by Yun et al (1) and Belcastro et al (2) describing palinopsia as a side effect of topiramate. This rare phenomenon, in which viewed images persist after the original visual stimulus is removed, can last from minutes to months (3). We evaluated a patient with acetazolamide-induced palinopsia. A 30-year-old obese woman, with previously treated idiopathic intracranial hypertension, complained of pulsatile tinnitus and chronic headache for a month. Examination revealed 20/20 visual acuity in each eye, normal ocular motility, full confrontational fields, and bilateral optic disc Simon R. Cardenas, MD Department of Neurology, Universidad Nacional Facultad de Medicina, Bogota, Colombia The authors report no conflicts of interest. REFERENCE 1. Cardenas SR, Saber Tehrani AS, Blume G, Kattah JC. Visual, ocular motor and cochleo-vestibular loss in patients with heteroplasmic maternally-inherited diabetes mellitus and deafness (MIDD), 3243 Transfer RNA Mutation. J Neuroophthalmol. 2016. in press. swelling. She was counseled about nutritional and low sodium dieting and prescribed acetazolamide 500 mg twice a day for 2 weeks and increased 1 tablet per week until tolerance of 2,000 mg daily. At that dose, she reported paresthesias in hands and feet, carbonation taste changes, difficulty concentrating, and cloudy urine. When stressed or when moving her hand in front of her face, the patient noted "ghost images" trailing her hand. Two months later, she expressed a desire to decrease the dose of acetazolamide due to the unpleasant side effects. Ophthalmic examination was unchanged. Acetazolamide was decreased to 1,500 mg and aggressive weight loss encouraged. However, the visual trailing effect became more frequent. She also experienced 2 new peculiar visual and tactile symptoms. She described seeing an image on FIG. 1. Illustration of persistent afterimage. Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 343-352 347 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.