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ARTICLES: K.A.M. Majamaa-Voltti, S. Winqvist, A. M. Remes, U. Tolonen, J. Pyhtinen, S. Uimonen, M. Kärppä, M. Sorri, K. Peuhkurinen, and K. Majamaa A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA Neurology 2006; 66: 1470-1475 [Abstract] [Full text] [PDF]

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A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA

Josef Finsterer, Claudia Stollberger   (31 August 2006)

A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA 31 August 2006
Josef Finsterer, KAR Postfach 20, 1180 Vienna, Austria, Claudia Stollberger Send Correspondence to journal: Re: A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA fipaps{at}yahoo.de Josef Finsterer, et al.	We read with interest the article by Majamaa-Voltti et al on the phenotype and genotype progression of 33 MELAS patients carrying the mitochondrial A3243G mutation over three years. [1] The article raises the following concerns: Mitochondrial disorders, including MELAS, are usually multi-system disorders, at least after a disease course of several years.[2] A system frequently affected by mitochondrial mutations is the endocrine system. Which other endocrine abnormalities were observed in addition to short stature and diabetes? Were there any ophthalmologic, renal dermal or gastrointestinal abnormalities? How severely was the skeletal muscle affected and did muscle affection progress over time? How many had seizures? How many reported migraine-like headache? Which type of headache mentioned in table 1 did the authors observe? How many had heart failure? Did any patient also present with left-ventricular noncompaction (frequently associated with mitochondrial disorders)? [3] MELAS is per definition characterized by lactacidosis but lactate may be also increased in the CSF, particularly if there is CNS involvement.[4] How many of the 33 underwent a spinal tap and how often was CSF lactate elevated? Did any patient present with lactacidosis? Though all patients carried the A3243G mutation it is not mentioned in how many the mutation was inherited or de novo? No explanations are provided why left-ventricular wall-thickness particularly increased in diabetic patients during follow-up. Do these patients require a thickened myocardium to overcome an increased resistance of the diabetic angiopathic arteries? Was the mutation load higher in these patients? There is also no explanation provided for the inverse relation between the heteroplasmy rate in leukocytes and age. Usually, heteroplasmy increases with age. [2] Are cells with high mutation load preferentially removed? [5] How to explain the significantly higher cognitive decline in men as compared to women? How to explain the three times higher rate of stroke-like-episodes and neuropathy in men as compared with women? Did those with cognitive decline more often have epilepsy, basal ganglia calcification, ataxia, or stroke-like episodes? No information is given on the therapy. Did those who received specific or non-specific therapy differ concerning their progression and outcome? Was there any need to modify therapy during the three years, particularly anti -epileptic or cardiac therapy? Did the three patients with atrial fibrillation also receive oral anticoagulation? Did the four patients who died suddenly decease from cardiac or extra- cardiac causes? Though the presented data confirm that MELAS is most frequently a multi- system disease and progresses over time, many observations remain unexplained. References 1. Majamaa-Voltti KA, Winqvist S, et al. A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA. Neurology 2006;66:1470-1475. 2. Zeviani M, Di Donato S. Mitochondrial disorders. Brain 2004;127:2153-2172. 3. Pignatelli RH, McMahon CJ, Dreyer WJ, et al. Clinical characterization of left ventricular noncompaction in children: a relatively common form of cardiomyopathy. Circulation 2003;108:2672-2678. 4 Kaufmann P, Shungu DC, Sano MC, et al. Cerebral lactic acidosis correlates with neurological impairment in MELAS. Neurology 2004;62:1297-1302. 5 Lynn S, Borthwick GM, Charnley RM, Walker M, Turnbull DM. Heteroplasmic ratio of the A3243G mitochondrial DNA mutation in single pancreatic beta cells. Diabetologia 2003;46:296-299. Disclosure: The authors report no conflicts of interest. The authors had the opportunity to reply but declined.